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  1. Pulmonary arterial hypertension in rats due to age-related arginase activation in intermittent hypoxia.

    PubMed

    Nara, Akina; Nagai, Hisashi; Shintani-Ishida, Kaori; Ogura, Sayoko; Shimosawa, Tatsuo; Kuwahira, Ichiro; Shirai, Mikiyasu; Yoshida, Ken-ichi

    2015-08-01

    Pulmonary arterial hypertension (PAH) is prevalent in patients with obstructive sleep apnea syndrome (OSAS). Aging induces arginase activation and reduces nitric oxide (NO) production in the arteries. Intermittent hypoxia (IH), conferred by cycles of brief hypoxia and normoxia, contributes to OSAS pathogenesis. Here, we studied the role of arginase and aging in the pathogenesis of PAH in adult (9-mo-old) and young (2-mo-old) male Sprague-Dawley rats subjected to IH or normoxia for 4 weeks and analyzed them with a pressure-volume catheter inserted into the right ventricle (RV) and by pulsed Doppler echocardiography. Western blot analysis was conducted on arginase, NO synthase isoforms, and nitrotyrosine. IH induced PAH, as shown by increased RV systolic pressure and RV hypertrophy, in adult rats but not in young rats. IH increased expression levels of arginase I and II proteins in the adult rats. IH also increased arginase I expression in the pulmonary artery endothelium and arginase II in the pulmonary artery adventitia. Furthermore, IH reduced pulmonary levels of nitrate and nitrite but increased nitrotyrosine levels in adult rats. An arginase inhibitor (N(ω)-hydroxy-nor-1-arginine) prevented IH-induced PAH and normalized nitrite and nitrate levels in adult rats. IH induced arginase up-regulation and PAH in adult rats, but not in young rats, through reduced NO production. Our findings suggest that arginase inhibition prevents or reverses PAH. PMID:25490411

  2. Arterial hypertension due to fructose ingestion: model based on intermittent osmotic fluid trapping in the small bowel

    PubMed Central

    2010-01-01

    Based on recently reported data that fructose ingestion is linked to arterial hypertension, a model of regulatory loops involving the colon role in maintenance of fluid and sodium homeostasis is proposed. In normal digestion of hyperosmolar fluids, also in cases of postprandial hypotension and in patients having the "dumping" syndrome after gastric surgery, any hyperosmolar intestinal content is diluted by water taken from circulation and being trapped in the bowel until reabsorption. High fructose corn sirup (HFCS) soft drinks are among common hyperosmolar drinks. Fructose is slowly absorbed through passive carrier-mediated facilitated diffusion, along the entire small bowel, thus preventing absorption of the trapped water for several hours. Here presented interpretation is that ingestion of hyperosmolar HFCS drinks due to a transient fluid shift into the small bowel increases renin secretion and sympathetic activity, leading to rise in ADH and aldosterone secretions. Their actions spare water and sodium in the large bowel and kidneys. Alteration of colon absorption due to hormone exposure depends on cell renewal and takes days to develop, so the momentary capacity of sodium absorption in the colon depends on the average aldosterone and ADH exposure during few previous days. This inertia in modulation of the colon function can make an individual that often takes HFCS drinks prone to sodium retention, until a new balance is reached with an expanded ECF pool and arterial hypertension. In individuals with impaired fructose absorption, even a higher risk of arterial hypertension can be expected. PMID:20579372

  3. Pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  4. Pulmonary arterial hypertension.

    PubMed

    Montani, David; Günther, Sven; Dorfmüller, Peter; Perros, Frédéric; Girerd, Barbara; Garcia, Gilles; Jaïs, Xavier; Savale, Laurent; Artaud-Macari, Elise; Price, Laura C; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role

  5. Idiopathic pulmonary arterial hypertension.

    PubMed

    Souza, Rogerio; Jardim, Carlos; Humbert, Marc

    2013-10-01

    Idiopathic pulmonary arterial hypertension (IPAH), formerly called primary pulmonary hypertension, is a rare disease (incidence and prevalence rates of approximately one and six cases per million inhabitants, respectively) with different clinical phenotypes. A group of diverse conditions manifest pulmonary arterial hypertension (PAH) and share similar pathological and/or clinical findings with IPAH. By definition, IPAH is diagnosed only after alternative diagnoses have been ruled out. Extensive investigation is needed to determine if PAH is associated with thyroid diseases, infectious diseases, autoimmune conditions, exposure to certain drugs (particularly anorexigens), certain genetic mutations, and so on. The presence of genetic abnormalities and risk factors (such as specific drug exposures) reinforces the "multiple hit" concept for the development of pulmonary hypertension. Fortunately, within the past two decades, therapeutic options have become available for IPAH, resulting in improved survival and clinical outcomes. At least seven different compounds have been registered for PAH treatment. However, even with aggressive PAH-specific therapy, mortality rates remain high (∼40% at 5 years). Given the high mortality rates, the use of combinations of agents that work by different pathways has been advocated (either as "add-on" therapy or initial "up front" therapy). Further, new therapeutic agents and treatment strategies are on the near horizon, aiming to further improve survival from the remarkable progress already seen. PMID:24037625

  6. Pulmonary Arterial Hypertension

    MedlinePlus

    ... What Is Pulmonary Hypertension? To understand pulmonary hypertension (PH) it helps to understand how blood ows throughout ... is too high, it is called pulmonary hypertension (PH). How the pressure in the right side of ...

  7. Ventricular repolarization before and after treatment in patients with secondary hypertension due to renal-artery stenosis and primary aldosteronism.

    PubMed

    Maule, Simona; Bertello, Chiara; Rabbia, Franco; Milan, Alberto; Mulatero, Paolo; Milazzo, Valeria; Papotti, Grazia; Veglio, Franco

    2011-10-01

    A prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects. Patients with renal-artery stenosis and primary aldosteronism (PA) are at increased risk of cardiovascular events. The objective of the present study was to evaluate the QT interval in patients with renovascular hypertension (RV) and PA before and after treatment. A total of 24 patients with RV and 38 with PA were studied; 89 patients with essential hypertension (EH) served as control group. Corrected QT intervals (QTcH) were measured from a 12-lead ECG. Basal QTcH was longer in RV (429±30 ms) and PA (423±23 ms) compared with EH controls (407±18 ms; P<0.001). The prevalence of QTcH >440 ms was higher in RV (29%) and PA patients (29%) compared with EH controls (4%; P<0.001). QTcH interval was evaluated after treatment in 19 RV and 15 PA patients. QTcH was reduced after renal-artery angioplasty in RV patients (419±14 ms; P=0.02), and after spironolactone or adrenalectomy in PA (403±12 ms; P=0.01). In conclusion, QT interval was prolonged in patients with RV and PA compared with controls with EH. After angioplasty of renal-artery stenosis in RV, and treatment with spironolactone or adrenalectomy in PA, the cardiovascular risk of such patients may be reduced by concomitant blood pressure lowering and QT duration shortening. PMID:21677661

  8. Anticoagulation in Pulmonary Arterial Hypertension.

    PubMed

    Robinson, Jeffrey C; Pugliese, Steven C; Fox, Daniel L; Badesch, David B

    2016-06-01

    Pulmonary arterial hypertension (PAH) is characterized by molecular and pathologic alteration to the pulmonary circulation, resulting in increased pulmonary vascular resistance, right ventricular failure, and eventual death. Pharmacologic treatment of PAH consists of use of a multitude of pulmonary vasodilators, sometimes in combination. PAH has been associated with increased thrombosis and disrupted coagulation and fibrinolysis, making anticoagulation an attractive and frequently employed therapeutic modality. Observational studies have provided some insight into the therapeutic potential of anticoagulation in idiopathic PAH, but there is a distinct lack of well-controlled prospective trials. Due to the conflicting evidence, there is a large amount of heterogeneity in the application of therapeutic anticoagulation in PAH and further well-controlled prospective trials are needed to clarify its role in treating PAH. PMID:27137522

  9. [PREDICTORS OF RESISTANT ARTERIAL HYPERTENSION].

    PubMed

    Lazutkina, A Y; Gorbunov, V V

    2016-01-01

    The paper reports results of 6 year prospective observation of 7959 members of locomotive crews engaged at the Transbaikal Railways. The study aimed to estimate the probability and time of development of resistant arterial hypertension under effect of predictors of this disease. The data obtained are of value for diagnostic, prophylactic, and therapeutic practice. PMID:27522725

  10. New therapies for arterial hypertension.

    PubMed

    Pagliaro, Beniamino; Santolamazza, Caterina; Rubattu, Speranza; Volpe, Massimo

    2016-03-01

    Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures. PMID:26730462

  11. [Drugs: an underestimated cause of arterial hypertension].

    PubMed

    Serveaux, Marianne; Burnier, Michel; Pruijm, Menno

    2014-09-10

    In Switzerland, as in other Occidental countries, the prevalence of arterial hypertension (AHT) in the adult population is around 30-40%. Among the causes of secondary AHT, drug induced hypertension is sometimes omitted. Many molecules can induce AHT or worsen it due to an interaction with anti hypertensive drugs. Among these, NSAIDs and anti depressants, widely prescribed, should be used with caution, particularly in patients at risk, namely: those with preexisting AHT, the elderly, or patients suffering from kidney disease, diabetes, and/or heart failure. Increases in blood pressure have also been described with anti-vascular endothelial growth factor (VEGF) drugs, used in the treatment of (metastatic) cancer. A thorough anamnesis of drugs, including over the counter ones, should be performed in every hypertensive patient, and can avoid cumbersome and unnecessary investigations and therapy. PMID:25322625

  12. [Chronotherapy in arterial hypertension].

    PubMed

    Bendersky, M

    2015-01-01

    The blood pressure profile in most normo- and hypertensive subjects are currently known, as well as the impact their changes induced on the cardio- and cerebrovascular risk. Ambulatory blood pressure monitoring (ABPM) has contributed greatly to the knowledge of this parameter. It to correct the schedule of drug administration (chronotherapy) with changes in any component of the BP profile that have better correlation with risk. These include the nocturnal decrease and the morning BP surge. Investigations in this direction are still scarce, and multicenter studies need to be conducted that can answer the true preventive impact of such modifications. PMID:26180036

  13. Arrhythmias in pulmonary arterial hypertension.

    PubMed

    Rajdev, Archana; Garan, Hasan; Biviano, Angelo

    2012-01-01

    Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914

  14. Arrhythmias in Pulmonary Arterial Hypertension

    PubMed Central

    Rajdev, Archana; Garan, Hasan; Biviano, Angelo

    2013-01-01

    Cardiac arrhythmias are important contributors to morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Such patients manifest a substrate resulting from altered autonomics, repolarization abnormalities, and ischemia. Supraventricular arrhythmias such as atrial fibrillation and flutter are associated with worsened outcomes, and maintenance of sinus rhythm is a goal. Sudden death is a relatively common issue, though the contribution of malignant ventricular arrhythmias versus bradyarrhythmias differs from non-PAH patients. Congenital heart disease patients with PAH benefit from catheter ablation of medically refractory arrhythmias. Clinical studies of defibrillator/pacemaker therapy for primary prevention against sudden death in PAH patients are lacking. PMID:23009914

  15. [Treatment of pulmonary arterial hypertension].

    PubMed

    Roman, Antonio; López-Meseguer, Manuel; Domingo, Enric

    2015-06-22

    Treatment of pulmonary arterial hypertension has achieved significant progress over the past 20 years. Currently, 3 groups of drugs have proven useful for the treatment of this disease: endothelin receptor antagonist, phosphodiesterase inhibitors and prostacyclin and its analogues. It is recommended to initiate treatment with one of these drugs, the choice depending on the initial severity of patient disease and the preferences of the treating physician. When the patient does not have a satisfactory response, new drugs acting at a different pathway are most commonly added. At this time, considering referral for lung transplantation could be an alternative. Most experts recommend grouping maximum experience in what is known as expert centers. Treatment has led to better survival in these patients, but there is still a long way to cure this life-threatening disease. PMID:25070518

  16. Drugs induced pulmonary arterial hypertension.

    PubMed

    Seferian, Andrei; Chaumais, Marie-Camille; Savale, Laurent; Günther, Sven; Tubert-Bitter, Pascale; Humbert, Marc; Montani, David

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of the pulmonary microvasculature, resulting in elevated pulmonary vascular resistance and premature death. According to the current classification, PAH can be associated with exposure to certain drugs or toxins, particularly appetite suppressant drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary arterial smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used but are also considered as possible risk factors for PAH. Dasatinib, a dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, in part reversible after its withdrawal. Recently several studies raised the potential endothelial dysfunction that could be induced by interferon, and few cases of PAH have been reported with interferon therapy. Other possible risk factors for PAH include: nasal decongestants, like phenylpropanolamine, dietary supplement - L-Tryptophan, selective serotonin reuptake inhibitors, pergolide and other drugs that could act on 5HT2B receptors. Interestingly, PAH remains a rare complication of these drugs, suggesting possible individual susceptibility and further studies are needed to identify patients at risk of drugs induced PAH. PMID:23972547

  17. Iranian Pulmonary Arterial Hypertension Registry

    PubMed Central

    Fahimi, Fanak; Sharif-Kashani, Babak; Malek Mohammad, Majid; Saliminejad, Leila; Monjazebi, Fateme

    2015-01-01

    Background: Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disorder with a prevalence of 8.6 per million. We introduce a registry website for IPAH and PAH patients ( www.IPAH.ir) for access and efficient delivery of government-aided and subsidized antihypertensive medications. Materials and Methods: The IPAH registry was opened in November 2009. Information of IPAH and PAH patients with a username and password were uploaded in the site. Data entry was possible only via the physicians and healthcare organizations via internet that were given a personalized username and password for entry. Following the patients’ profile submission, a scientific committee composed of a cardiologist and a pulmonologist who were selected by the Ministry of Health of Iran (MOH), evaluated the data. The eligibility of the patient to receive the medications was confirmed after evaluation. If the patient was eligible, 82% of the Bosentan cost was paid by MOH. Results: To date, one hundred and sixteen patients (82 females, 34 males) have been registered. The mean pulmonary artery pressure by right heart catheterization was 69.24±17 mmHg (ranging from 35 to 110 mmHg). Conclusion: The first online Iranian registry program for IPAH and PAH patients is believed to supply essential information for health care providers in the field. PMID:26528365

  18. A Novel Channelopathy in Pulmonary Arterial Hypertension

    PubMed Central

    Austin, Eric D.; Eyries, Mélanie; Sampson, Kevin S.; Soubrier, Florent; Germain, Marine; Trégouët, David-Alexandre; Borczuk, Alain; Rosenzweig, Erika Berman; Girerd, Barbara; Montani, David; Humbert, Marc; Loyd, James E.; Kass, Robert S.; Chung, Wendy K.

    2013-01-01

    BACKGROUND Pulmonary arterial hypertension is a devastating disease with high mortality. Familial cases of pulmonary arterial hypertension are usually characterized by autosomal dominant transmission with reduced penetrance, and some familial cases have unknown genetic causes. METHODS We studied a family in which multiple members had pulmonary arterial hypertension without identifiable mutations in any of the genes known to be associated with the disease, including BMPR2, ALK1, ENG, SMAD9, and CAV1. Three family members were studied with whole-exome sequencing. Additional patients with familial or idiopathic pulmonary arterial hypertension were screened for the mutations in the gene that was identified on whole-exome sequencing. All variants were expressed in COS-7 cells, and channel function was studied by means of patch-clamp analysis. RESULTS We identified a novel heterozygous missense variant c.608 G→A (G203D) in KCNK3 (the gene encoding potassium channel subfamily K, member 3) as a disease-causing candidate gene in the family. Five additional heterozygous missense variants in KCNK3 were independently identified in 92 unrelated patients with familial pulmonary arterial hypertension and 230 patients with idiopathic pulmonary arterial hypertension. We used in silico bioinformatic tools to predict that all six novel variants would be damaging. Electrophysiological studies of the channel indicated that all these missense mutations resulted in loss of function, and the reduction in the potassium-channel current was remedied by the application of the phospholipase inhibitor ONO-RS-082. CONCLUSIONS Our study identified the association of a novel gene, KCNK3, with familial and idiopathic pulmonary arterial hypertension. Mutations in this gene produced reduced potassium-channel current, which was successfully remedied by pharmacologic manipulation. (Funded by the National Institutes of Health.) PMID:23883380

  19. Medical treatment update on pulmonary arterial hypertension

    PubMed Central

    Burger, Charles

    2015-01-01

    Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed. PMID:26336595

  20. Management of pulmonary arterial hypertension associated with congenital heart disease.

    PubMed

    Togănel, Rodica; Benedek, I; Suteu, Carmen; Blesneac, Cristina

    2007-01-01

    Congenital heart diseases are the most common congenital malformations and account for about eight cases per 1000 births and are often associated with pulmonary arterial hypertension. Increased shear stress and the excess flow through the pulmonary vascular bed due to a systemic-to-pulmonary shunt lead to the development of pulmonary vascular disease and an increase in pulmonary vascular resistance. Without surgical repair approximately 30% of patients develop pulmonary vascular disease. Eisenmenger syndrome represents the extreme end of pulmonary arterial hypertension with congenital heart disease. We summarized the current therapeutic options for pulmonary arterial hypertension; conventional treatments including calcium channel blockers, anticoagulation, digitalis, diuretics, and new treatment: prostacyclin, bosentan, sildenafil, ambrisentan. Preliminary data of new therapies are encouraging with disease significantly improved natural history, but there is need for more evidence-based data. PMID:18333354

  1. Recent trends in pulmonary arterial hypertension

    PubMed Central

    Natarajan, Rajagopalan

    2011-01-01

    Pulmonary hypertension is a serious and unrelenting pulmonary vascular disorder that affects the functional quality of patients and significantly decreases their life span. If diagnosed early, with the number of new therapeutic options that are available, a better quality of life can be provided for a protracted length of time. It is likely that the available treatment will change the natural course of the disease and perhaps prolong survival. As symptoms are often subtle in the early stages of the disease it is imperative that physicians are aware of the manifestations of this condition. A thorough investigation of patients suspected of this condition is essential so that appropriate treatment can be initiated promptly. The routine workup of a patient suspected to have pulmonary hypertension could easily be carried out in any well-equipped peripheral hospital in many affluent and advanced countries. However, it must be mentioned that in some less advanced countries the necessary work up can only be done in major teaching hospitals. Both pulmonologists and cardiologists should be aware of the pathophysiology of pulmonary arterial hypertension, the workup and the treatment options that are available. Patients with refractory pulmonary hypertension should be referred to these research centers for enrolment into any ongoing drug trials as well as for evaluation for heart–lung, single lung, or double lung transplantation. This paper is primarily aimed at pulmonologists and cardiologists taking care of these patients. Unless indicated otherwise this paper mainly deals with WHO group 1 pulmonary hypertension which is designated pulmonary arterial hypertension. Extensive review of the literature spanning the last 30 years was made through Medline using titles such as primary pulmonary hypertension, pulmonary arterial hypertension, secondary pulmonary hypertension, and pulmonary vascular diseases. PMID:21654985

  2. Pulmonary arterial hypertension in primary amyloidosis

    PubMed Central

    Emerson, Lyska L.; Bull, David A.; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C.; Ryan, John J.

    2016-01-01

    Abstract Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852

  3. Pulmonary arterial hypertension in primary amyloidosis.

    PubMed

    Cirulis, Meghan M; Emerson, Lyska L; Bull, David A; Hatton, Nathan; Nativi-Nicolai, Jose; Hildebrandt, Gerhard C; Ryan, John J

    2016-06-01

    Amyloidosis involves extravascular deposition of fibrillar proteins within tissues and organs. Primary light chain amyloidosis represents the most common form of systemic amyloidosis involving deposition of monoclonal immunoglobulin light chains. Although pulmonary amyloid deposition is common in primary amyloidosis, clinically significant pulmonary amyloidosis is uncommon, and elevated pulmonary artery pressures are rarely observed in the absence of other underlying etiologies for pulmonary hypertension, such as elevated filling pressures secondary to cardiac amyloid. In this case report, we present a patient with primary light chain amyloidosis and pulmonary arterial hypertension in the setting of pulmonary vascular and right ventricular myocardial amyloid deposition. PMID:27252852

  4. Hemorheological abnormalities in human arterial hypertension

    NASA Astrophysics Data System (ADS)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  5. Diagnosis and Management of Pulmonary Arterial Hypertension

    PubMed Central

    Houtchens, Jeanne; Martin, Douglas; Klinger, James R.

    2011-01-01

    Pulmonary arterial hypertension is a rare disease, which requires a high index of suspicion to diagnose when patients initially present. Initial symptoms can be nonspecific and include complaints such as fatigue and mild dyspnea. Once the disease is suspected, echocardiography is used to estimate the pulmonary arterial (PA) pressure and to exclude secondary causes of elevated PA pressures such as left heart disease. Right heart catheterization with vasodilator challenge is critical to the proper assessment of pulmonary hemodynamics and to determine whether patients are likely to benefit from vasodilator therapy. Pathologically, the disease is characterized by deleterious remodeling of the distal pulmonary arterial and arteriolar circulation, which results in increased pulmonary vascular resistance. In the last fifteen years, medications from three different classes have been approved for the treatment of pulmonary arterial hypertension. These include the prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. PMID:21941650

  6. Arterial hypertension – prevalence of risk factors and morbide associations that increase cardiovascular risk

    PubMed Central

    Sur, G; Sur, M; Kudor-Szabadi, L; Sur, L; Sporis, D; Sur, D

    2010-01-01

    ABSTRACT Hypertension represents a serious problem in Romania, as there are over 3 million hypertensive people in our country. There is a high incidence of deaths caused by hypertension. We performed an analytical prospective study that aims to determine: prevalence of arterial hypertension in a population from Cluj county, distribution on age and gender, arterial hypertension severity, association of hypertension with other cardiovascular risk factors. Our study included 2266 patients, age 14 years old up to over 90 years old, both masculine and feminine gender, known with hypertension and new-diagnosed ones. Each subject was submitted to an interview based on a questionnaire. Diagnosis of arterial hypertension was established according to ESH criteria that consider as hypertension: values over 140/90 mmHg. Out of all subjects submitted to the study 647 (29.74%) were diagnosed with arterial hypertension and, from these, 102 (15.13%) were new-diagnosed patients. We found out a predominance of arterial hypertension at the age of 51-60 and over 60, an increased involvement of feminine sex; an association of hypertension with other major cardiovascular risk factors: obesity, diabetes, dislypidemia. Arterial hypertension represents an important health problem in Romania due to an increased prevalence, major impact on morbidity and mortality by cardiovascular and cerebro-vascular disease. These facts accentuate the necessity of an early diagnosis, of making people aware of the severity of the disease and it’s impact on their lifestyle. PMID:21977116

  7. [Risk factors for arterial hypertension among machinery construction workers].

    PubMed

    Zakhar'eva, S V; Pasechnaia, N A

    2006-01-01

    The authors studied prevalence of arterial hypertension, its risk factors in workers of major machinery construction enterprise, who have prolonged contact with a complex of low-intensity occupational hazards. Findings are reliably higher prevalence of arterial hypertension among the workers vs. reference group, relative risk of arterial hypertension responding to exposed factor. PMID:16491856

  8. Medical therapies for pulmonary arterial hypertension.

    PubMed

    Pulido, Tomas; Zayas, Nayeli; de Mendieta, Maitane Alonso; Plascencia, Karen; Escobar, Jennifer

    2016-05-01

    Pulmonary Arterial hypertension (PAH) is a chronic and progressive disease characterized by an increase in pulmonary vascular resistance due to severe remodeling of the small pulmonary arteries. In PAH, the endothelial cells fail to maintain their homeostatic balance, with the consequent impaired production of vasodilators and over-expression of vasoconstrictors and proliferators. Current treatment of PAH is based on the discovery of three main pathways of endothelial dysfunction (prostacyclin, nitric oxide and endothelin-1), and includes drugs such as prostacyclin analogs, phosphodiesterase-5 inhibitors and endothelin receptor antagonists (ERAs). Recently approved drugs that act through these classic pathways include riociguat (cyclic GMP stimulator) and macitentan (a tissue specific dual ERA). However, several new drugs and new pathways are under study. New targeted therapies include tyrosine kinase inhibitors, Rho kinase inhibitors and serotonin receptor blockers. There are now ten drugs approved for the treatment of PAH that, alone or in combination, have changed the natural history of this disease. The new drugs will allow us to further modified the patients' life expectancy and move towards a cure. PMID:26791159

  9. MicroRNAs in Pulmonary Arterial Hypertension

    PubMed Central

    Zhou, Guofei; Chen, Tianji

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340

  10. MicroRNAs in pulmonary arterial hypertension.

    PubMed

    Zhou, Guofei; Chen, Tianji; Raj, J Usha

    2015-02-01

    Pulmonary arterial hypertension (PAH) is a devastating disease without effective treatment. Despite decades of research and the development of novel treatments, PAH remains a fatal disease, suggesting an urgent need for better understanding of the pathogenesis of PAH. Recent studies suggest that microRNAs (miRNAs) are dysregulated in patients with PAH and in experimental pulmonary hypertension. Furthermore, normalization of a few miRNAs is reported to inhibit experimental pulmonary hypertension. We have reviewed the current knowledge about miRNA biogenesis, miRNA expression pattern, and their roles in regulation of pulmonary artery smooth muscle cells, endothelial cells, and fibroblasts. We have also identified emerging trends in our understanding of the role of miRNAs in the pathogenesis of PAH and propose future studies that might lead to novel therapeutic strategies for the treatment of PAH. PMID:25192340

  11. [Hypertensive crises in patients with arterial hypertension in ambulatory treatment].

    PubMed

    Gomes Guedes, Nirla; Chaves Costa, Francisca Bertilia; Moreira, Rafaella Pessoa; Moreira, Tahissa Frota; Soares Chavess, Emilia; de Araújo, Thelma Leite

    2005-06-01

    This study assessed the sociodemographic characteristics and the characteristics of therapeutic adhesion of 27 bearers of arterial hypertension undergoing ambulatorial treatment who had hypertensive urgencies crises or emergencies in the city of Fortaleza in the period between October of 2002 and May of 2003. The majority were women, between 50 and 60-years old, with little formal education, treatment time shorter than 5 years and time of diagnosis varying from 5 to 10 years. The use of medicine was the treatment that was most mentioned, followed by the reduction of the consumption of salt and attendance to medical appointments. However, attending the appointments and receiving orientation did not seem to change their behavior, since most of the patients that were interviewed practiced no physical exercises and demonstrated little knowledge of the illness, for they attributed the rise of the arterial pressure to emotional factors. PMID:16060305

  12. Pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: pathophysiology.

    PubMed

    Humbert, M

    2010-03-01

    Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are two of the key subgroups of pulmonary hypertension. They are characterised by different risk factors. PAH can be associated with mutations in the gene encoding bone morphogenetic protein receptor type II (BMPR2), HIV infection, congenital heart disease, connective tissue disease (such as systemic sclerosis), and exposure to particular drugs and toxins including fenfluramine derivatives. In contrast, CTEPH can be associated with anti-phospholipid antibodies, splenectomy and the presence of a ventriculo-atrial shunt or an infected pacemaker. The first-line therapies used to treat PAH and CTEPH also differ. While medical therapy tends to be used for patients with PAH, pulmonary endarterectomy is the treatment of choice for patients with CTEPH. However, there are possible common mechanisms behind the two diseases, including endothelial cell dysfunction and distal pulmonary artery remodelling. Further research into these similarities is needed to assist the development of targeted pharmacological therapies for patients with inoperable CTEPH and patients who have persistent pulmonary hypertension after endarterectomy. PMID:20956167

  13. Human Immunodeficiency Virus and Pulmonary Arterial Hypertension

    PubMed Central

    Ali, Alaa M.

    2013-01-01

    Human immunodeficiency virus- (HIV-) related pulmonary arterial hypertension (PAH) is a rare complication of HIV infection. The pathophysiology of HIV-related PAH is complex, with viral proteins seeming to play the major role. However, other factors, such as coinfection with other microorganisms and HIV-related systemic inflammation, might also contribute. The clinical presentation of HIV-related PAH and diagnosis is similar to other forms of pulmonary hypertension. Both PAH-specific therapies and HAART are important in HIV-related PAH management. Future studies investigating the pathogenesis are needed to discover new therapeutic targets and treatments. PMID:24027641

  14. Nitric Oxide, Oxidative Stress and Inflammation in Pulmonary Arterial Hypertension

    PubMed Central

    Crosswhite, Patrick; Sun, Zhongjie

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and progressive disease characterized by a persistent elevation of pulmonary artery pressure accompanied by right ventricular hypertrophy (RVH). The current treatment for pulmonary hypertension is limited and only provides symptomatic relief due to unknown etiology and pathogenesis of the disease. Both vasoconstriction and structural remodeling (enhanced proliferation of VSMC) of the pulmonary arteries contribute to the progressive course of PAH, irrespective of different underlying causes. The exact molecular mechanism of PAH, however, is not fully understood. The purpose of this review is to provide recent advances in the mechanistic investigation of PAH. Specifically, this review focuses on nitric oxide (NO), oxidative stress and inflammation and how these factors contribute to the development and progression of PAH. This review also discusses recent and potential therapeutic advancements for the treatment of PAH. PMID:20051913

  15. An Update on Pulmonary Arterial Hypertension

    PubMed Central

    Wapner, Joanna; Matura, Lea Ann

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease that ultimately leads to right heart failure and death. PAH is defined as a mean pulmonary arterial pressure ≥ 25 mm Hg with a pulmonary capillary wedge pressure ≤ 15 mm Hg at rest. The diagnosis of PAH is one of exclusion; diagnostics include an extensive history, serology, chest radiograph, pulmonary function tests, ventilation/perfusion scan, transthoracic echocardiogram, and right heart catheterization. Treatment and care of patients with PAH can be complex. Therefore, the nurse practitioner is an integral member of the healthcare team caring for PAH patients, helping to ensure seamless care and support. PMID:25954140

  16. Pulmonary Arterial Hypertension: The Clinical Syndrome

    PubMed Central

    Lai, Yen-Chun; Potoka, Karin C.; Champion, Hunter C.; Mora, Ana L.; Gladwin, Mark T.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disorder in which endothelial dysfunction and vascular remodeling obstruct small pulmonary arteries, resulting in increased pulmonary vascular resistance and pulmonary pressures. This leads to reduced cardiac output, right heart failure, and ultimately death. In this review, we attempt to answer some important questions commonly asked by patients diagnosed with PAH pertaining to the disease, and aim to provide an explanation in terms of classification, diagnosis, pathophysiology, genetic etiologies, demographics, and prognostic factors. Furthermore, important molecular pathways that are central to the pathogenesis of PAH are reviewed, including nitric oxide, prostacyclin, endothelin-1, reactive oxygen species, and endothelial and smooth muscle proliferation. PMID:24951762

  17. Pulmonary arterial hypertension: a clot in question.

    PubMed

    Patel, Bhavin; Pakala, Aneesh; Aronson, Willard; Magharyous, Hany; Brown, Brent

    2014-07-01

    Pulmonary arterial hypertension (PAH) is a group of disorders characterized by a progressive increase in pulmonary vascular resistance leading to right heart failure and premature death. We present an unusual case of PAH diagnosed initially as Idiopathic PAH (IPAH) after secondary causes were excluded which was successfully managed for a number of years with vasodilators and anticoagulation. Over the months after stopping anticoagulation (because of recurring small bowel hemorrhaging) patient developed progressive findings of right heart failure, which failed to respond to escalating doses of prostacyclin. The patient died and an autopsy revealed the surprising finding of extensive organized central pulmonary artery thrombi as is seen in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We discuss the question of whether these thrombi are generally embolic or develop in situ and recommend that clinicians have a high index of suspicion for central thrombi in patients with IPAH were anticoagulation is contraindicated. PMID:25223151

  18. Metabolomic Heterogeneity of Pulmonary Arterial Hypertension

    PubMed Central

    Zhao, Yidan; Peng, Jenny; Lu, Catherine; Hsin, Michael; Mura, Marco; Wu, Licun; Chu, Lei; Zamel, Ricardo; Machuca, Tiago; Waddell, Thomas; Liu, Mingyao; Keshavjee, Shaf; Granton, John; de Perrot, Marc

    2014-01-01

    Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. PMID:24533144

  19. [Combination treatment in pulmonary arterial hypertension].

    PubMed

    Kramer, Mordechai R

    2011-04-01

    In recent years, there has been a marked improvement in the treatment of pulmonary arterial hypertension (PAH) due to the development of targeted therapies. There are now several treatment options available--oral, inhaled, and those delivered by subcutaneous or intravenous methods. These treatments have greatly improved patient survival, which in the past was 2.5 years on average. Efficient treatment choice generally proceeds from oral therapies--PDE-5 inhibitors (sildenafil) and endothelin receptor antagonists (bosentan or ambrisentan)--to inhaled prostanoids (iloprost) or subcutaneous (treprostinil). Intravenous prostacyclins are used in treating the more severe cases. The different pathways of action of each class of drugs allow a synergistic effect of combination therapy similar to malignancy or patients in congestive heart failure. The updated treatment algorithm includes combinations of therapies that target different pathways. This article will review the literature regarding combination therapy for the treatment of PAH. Combining PAH therapies that target different pathways is now a well-established treatment option, based on numerous international clinical trials, and offers new hope to patients suffering from this severe disease. PMID:22164922

  20. Update on pulmonary arterial hypertension pharmacotherapy.

    PubMed

    Velayati, Arash; Valerio, Marcos G; Shen, Michael; Tariq, Sohaib; Lanier, Gregg M; Aronow, Wilbert S

    2016-06-01

    Pulmonary artery hypertension (PAH) refers to several subgroups of disease in which the mean pulmonary artery pressure (mPAP) is elevated to more than 25 mm Hg, pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg, and an elevated pulmonary vascular resistance (PVR) > 3 Wood units as confirmed by right heart catheterization. The prevalence and geographic distribution of PAH vary depending on the type and etiology of the disease. Despite enormous efforts in the research and development of therapeutic agents in the last twenty years, the disease remains relatively incurable and the overall prognosis remains guarded. Median survival for an untreated patient is 2.8 years. In the last three decades, there have been dramatic advances in understanding the molecular mechanisms and signaling pathways involved in the disease, resulting in emerging new treatment strategies. In the following pages, we will review currently approved treatments for PAH, as well as a new generation of investigational drugs. PMID:27232660

  1. Initial experience with Tadalafil in Pediatric Pulmonary Arterial Hypertension

    PubMed Central

    Takatsuki, Shinichi; Calderbank, Michelle; Ivy, David Dunbar

    2012-01-01

    Summary Our objective was to investigate the safety, tolerability, and effects of tadalafil in children with pulmonary arterial hypertension after transition from sildenafil or receiving tadalafil as initial therapy. Thirty three pediatric patients with pulmonary arterial hypertension were retrospectively evaluated. Twenty nine of 33 patients were switched from sildenafil to tadalafil. The main reason for changing from sildenafil was once daily dosing. The average dose of sildenafil and tadalafil were 3.4+/−1.1 mg/kg/day and 1.0+/−0.4 mg/kg/day, respectively. In 14 of 29 patients undergoing repeat catheterization, statistically significant improvements were observed following transition from sildenafil to tadalafil, in mean pulmonary arterial pressure (mmHg) (53.2+/−18.3 versus 47.4+/−13.7, p<0.05) and pulmonary vascular resistance index (unitsxm2) (12.2+/−7.0 versus 10.6+/−7.2, p<0.05). In 4 patients treated with tadalafil as initial therapy, clinical improvement was noted. Side effect profiles were similar in patients who had transitioned from sildenafil to tadalafil and included headache, nausea, myalgia, nasal congestion, flushing, and allergic reaction. Two patients discontinued tadalafil due to migraine or an allergic reaction. One patient on sildenafil had no break through syncope after transition to tadalafil. Tadalafil can be safely used in pediatric patients with pulmonary arterial hypertension and may prevent disease progression. PMID:22402804

  2. Pulmonary hypertension due to isolated metastatic squamous cell carcinoma thromboemboli.

    PubMed

    Wilson, Michael K; Granger, Emily K; Preda, Veronica A

    2006-04-01

    Pulmonary hypertension as the initial presentation of occult malignancy is extremely rare. The differential diagnosis of pulmonary hypertension due to arterial tumour embolism is often overlooked and deserves contemplation. Our case report details the presentation of cardiorespiratory decompensation from an assumed classic saddle pulmonary embolus in a previously fit, well 80-year-old gentleman. The patient underwent successful pulmonary thromboendarterectomy, however, intraoperatively the specimen was noted to be atypical. This resulted in the surprising definitive diagnosis of thromboembolic pulmonary hypertension secondary to laminated thrombi of metastatic squamous cell tumour emboli. The site of tumour origin was however not histologically apparent and was unable to be elucidated on extensive further investigation. Post-operatively the patient had considerable subjective and functional improvement returning to activities of daily living. He however passed away some 9 months later. PMID:16412689

  3. Erythropoietin upregulation in pulmonary arterial hypertension.

    PubMed

    Karamanian, Vanesa A; Harhay, Michael; Grant, Gregory R; Palevsky, Harold I; Grizzle, William E; Zamanian, Roham T; Ihida-Stansbury, Kaori; Taichman, Darren B; Kawut, Steven M; Jones, Peter L

    2014-06-01

    The pathophysiologic alterations of patients with pulmonary arterial hypertension (PAH) are diverse. We aimed to determine novel pathogenic pathways from circulating proteins in patients with PAH. Multianalyte profiling (MAP) was used to measure 90 specifically selected antigens in the plasma of 113 PAH patients and 51 control patients. Erythropoietin (EPO) functional activity was assessed via in vitro pulmonary artery endothelial cell networking and smooth muscle cell proliferation assays. Fifty-eight patients had idiopathic PAH, whereas 55 had other forms of PAH; 5 had heritable PAH, 18 had connective tissue disease (15 with scleroderma and 3 with lupus erythematosis), 13 had portopulmonary hypertension, 6 had PAH associated with drugs or toxins, and 5 had congenital heart disease. The plasma-antigen profile of PAH revealed increased levels of several novel biomarkers, including EPO. Immune quantitative and histochemical studies revealed that EPO not only was significantly elevated in the plasma of PAH patients but also promoted pulmonary artery endothelial cell network formation and smooth muscle cell proliferation. MAP is a hypothesis-generating approach to identifying novel pathophysiologic pathways in PAH. EPO is upregulated in the circulation and lungs of patients with PAH and may affect endothelial and smooth muscle cell proliferation. PMID:25006446

  4. [Vascular aging, arterial hypertension and physical activity].

    PubMed

    Schmidt-Trucksäss, A; Weisser, B

    2011-11-01

    The present review delineates the significance of intima-media-thickness, arterial stiffness and endothelial function for vascular aging. There is profound evidence for an increase in intima-media-thickness and vascular stiffness not only during healthy aging but induced also by cardiovascular risk factors. There is a central role of arterial hypertension for this progression in both structural factors. In addition, both parameters are strongly associated with cardiovascular risk. Endothelial function measured as postischemic flow-mediated vasodilatation is a functional parameter which is decreased both in healthy aging and by cardiovascular risk factors. Physical activity modifies the influence of aging and risk factors on endothelial function. A positive influence of endurance exercise on vascular stiffness and endothelial function has been demonstrated in numerous studies. In long-term studies, regular physical activity has been shown to reduce the progression of intima-media-thickness. Thus, arterial hypertension accelerates vascular aging, while physical activity has a positive influence on a variety of vascular parameters associated with vascular aging. PMID:22068448

  5. Novel biomarkers for pulmonary arterial hypertension.

    PubMed

    Anwar, Anjum; Ruffenach, Gregoire; Mahajan, Aman; Eghbali, Mansoureh; Umar, Soban

    2016-01-01

    Pulmonary arterial hypertension is a deadly disease characterized by elevated pulmonary arterial pressures leading to right ventricular hypertrophy and failure. The confirmatory gold standard test is the invasive right heart catheterization. The disease course is monitored by pulmonary artery systolic pressure measurement via transthoracic echocardiography. A simple non-invasive test to frequently monitor the patients is much needed. Search for a novel biomarker that can be detected by a simple test is ongoing and many different options are being studied. Here we review some of the new and unique pre-clinical options for potential pulmonary hypertension biomarkers. These biomarkers can be broadly categorized based on their association with endothelial cell dysfunction, inflammation, epigenetics, cardiac function, oxidative stress, metabolism,extracellular matrix, and volatile compounds in exhaled breath condensate. A biomarker that can be detected in blood, urine or breath condensate and correlates with disease severity, progression and response to therapy may result in significant cost reduction and improved patient outcomes. PMID:27439993

  6. [Management of uncomplicated arterial hypertension in pregnancy].

    PubMed

    Gullotti, D; Gullotti, A; Schillaci, L; Lo Genco, A; Figlioli, F; Pira, M; Rotolo, G

    2006-02-01

    In the management of uncomplicated arterial hypertension in pregnancy, blood pressure (BP) values of pregnant women should be treated in order to reduce risks of both maternal and fetal complications. To reduce these risks, it is necessary to monitor BP, some hematochemical parameters and albuminuria, to try to prevent more serious clinical complications. Moreover, repeated measurements of BP, as well as frequent ambulatory blood pressure monitoring (ABPM) over 24 h are necessary. In the treatment of hypertension in pregnancy, if there are no high risks, it is possible to try a non pharmacological antihypertensive therapy consisting of a suitable diet, reduction of weight, abolition of some lifestyles (smoking, excessive alcohol consumption and heavy physical exercises). If these measures are not sufficient or the risk is high, a pharmacological therapy with neither toxic nor teratogenic drugs for the fetus will be administered in order to normalize BP without reducing perfusion of the uterus/placenta. Only in case of severe hypertension, a more aggressive pharmacological treatment should be carried out and, if necessary, hospitalization. The drugs suggested in these cases are those which have already been recognised as presenting low side effects. Antihypertensive drugs used in pregnancy can be classified as: suitable (methyldopa, clonidine, long acting calcioantagonists); cautiously used (alpha-blockers, beta-betablockers); contraindicated (ACE-inhibitors, sartans, short acting calcioantagonists). Hyper-tensive crises should be treated with an injection therapy (clonidine, labetalol), with hospital admission if necessary, or if preeclampsia or eclampsia may occur. PMID:16565702

  7. [Treatment of arterial hypertension in pregnancy in relation to current guidelines of the Polish Society of Arterial Hypertension from 2011].

    PubMed

    Szczepaniak-Chicheł, Ludwina; Tykarski, Andrzej

    2012-10-01

    Arterial hypertension concerns 7-10% of pregnancies and leads to an increased risk of complications for both, the mother and the child. This rate will probably rise in the years to come due to the notable tendency among women to delay the decision to become pregnant - values of blood pressure and occurrence of arterial hypertension increase with age, as well as due to the growing problem of obesity resulting from inappropriate dietary habits and lack of regular everyday physical activity. Difficulties with management of that clinical condition are partly related with lack of unified and widely accepted guidelines. Different opinions in the subject of terminology and classification of pregnancy hypertension or indications for pharmacotherapy as well as choice of the optimal antihypertensive drug, emerge from objective causes such as combination of various pathogenetic factors typical for arterial hypertension itself and those connected with pregnancy elsewhere stressed priorities of therapy from the point of view of the health of the mother and of the fetus, as well as lack of randomized clinical trials due to obvious ethical purposes, but also from the fact that pregnancy hypertension is a focus of attention for different specialists - obstetricians, hypertensiologists and perinatologists. A good cooperation regarding experience and information among all of these specializations would be the most beneficial for pregnant women and their children. Lack of new modern antihypertensive agents, safe and effective in pregnancy while the older ones are being withdrawn from the market as their production is no longer cost-effective for pharmacological companies, has become an increasing problem in many countries, and Poland among them. The aim of the following publication was to present the statement on management of pregnancy hypertension from the current guidelines of the Polish Society of Arterial Hypertension 2011 to gynecologists and obstetricians, with a commentary

  8. Advances in Pediatric Pulmonary Arterial Hypertension

    PubMed Central

    Ivy, Dunbar

    2012-01-01

    Purpose of Review Pulmonary arterial hypertension (PAH) is an important cause of morbidity and mortality in children. Approved medications for the treatment of adult PAH have been used to treat children but evidence based treatment algorithms for children are lacking. Recent Findings Pediatric PAH registries have begun to define the incidence and prevalence of idiopathic PAH and PAH associated with congenital heart disease. A pediatric specific classification of pulmonary hypertensive vascular disease has been proposed. Furthermore, the first randomized placebo-controlled trial of type-5 phosphodiesterase therapy in treatment naïve children with PAH has been completed and reported. This trial highlights the importance of the difficulties of performing clinical trials children with targeted PAH therapy as well as the importance of long-term follow-up of adverse events. Summary Classification, clinical trials, and therapy for children with PAH must take into account the unique aspects of PAH in children. PMID:22274573

  9. Inhaled treprostinil for the treatment of pulmonary arterial hypertension.

    PubMed

    Poms, Abby; Kingman, Martha

    2011-12-01

    Pulmonary arterial hypertension is a progressive disease characterized by vascular proliferation and vasoconstriction of the small pulmonary arteries that eventually leads to right-sided heart failure and death. Patients often initially have symptoms such as shortness of breath, fatigue, and edema; later in the disease, presyncope and syncope are common. Patients with progressive pulmonary arterial hypertension despite oral therapy and/or with severe disease typically require treatment with a prostanoid. Inhaled treprostinil (Tyvaso) is a prostacyclin analog indicated for the treatment of pulmonary arterial hypertension to increase walk distance in patients with symptoms classified as New York Heart Association functional class III. Inhaled treprostinil was approved by the Food and Drug Administration in July 2009. This article provides a brief overview of the pathophysiology of pulmonary arterial hypertension and reviews the mechanism of action, key clinical data, and the practical management of inhaled treprostinil in patients with pulmonary arterial hypertension. PMID:22135338

  10. Pericardial effusion in pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Abstract Pulmonary arterial hypertension (PAH) is a serious condition that can lead to right heart failure and death. Pericardial effusion in PAH is associated with significant morbidity and mortality, and its pathogenesis is complex and poorly understood. There are few data on the prevalence of pericardial effusion in PAH, and more importantly, the management of pericardial effusion is controversial. Current literature abounds with case reports, case series, and retrospective studies that have limited value for assessing this association. Hence, we summarize the available evidence on this ominous association and identify areas for future research. PMID:24618534

  11. "Nocturnal seizures" in idiopathic pulmonary arterial hypertension.

    PubMed

    Izzo, Anthony; McSweeney, Julia; Kulik, Thomas; Khatwa, Umakanth; Kothare, Sanjeev V

    2013-10-15

    The usual differential diagnoses of nocturnal events in children include parasomnias, nocturnal seizures, nocturnal reflux (Sandifer syndrome), hypnic jerks, periodic limb movements of sleep, and sleep disordered breathing. We report a previously healthy young girl who presented to the sleep clinic for evaluation of nocturnal events which were diagnosed as medically refractory nocturnal seizures. It was not until a syncopal event occurred in the daytime, which prompted referral for cardiac evaluation, the diagnosis of idiopathic pulmonary arterial hyper-tension (IPAH) was made. Sleep physicians should consider IPAH in the differential diagnosis of nocturnal events in children. PMID:24127156

  12. Pharmacotherapeutic management of pulmonary arterial hypertension.

    PubMed

    Anderson, Joe R; Nawarskas, James J

    2010-01-01

    Pulmonary arterial hypertension (PAH) is a disabling chronic disorder of the pulmonary vasculature, which is characterized by increased pulmonary artery pressure as a result of increased pulmonary vascular resistance. The pathology of PAH is characterized by pulmonary vascular vasoconstriction, smooth muscle cell proliferation, and thrombosis. These changes are a result of an imbalance between vasodilators (prostacyclin, nitric oxide, vasoactive intestinal peptide) and vasoconstrictors (thromboxane A2, endothelin, serotonin), growth inhibitors and mitogenic factors, and antithrombotic and prothrombotic factors. Recent advances in treatment are directed at restoring the balance between these systems. Endothelin receptor antagonists (bosentan, ambrisentan, sitaxsentan), phosphodiesterase type 5 inhibitors (sildenafil, tadalafil), and prostacylin (epoprostenol, iloprost, treprostinil, beraprost) represent the different classes of medications that are currently used in monotherapy and in combination to treat PAH. The purpose of this drug highlight is to provide the reader with an update of the pharmacotherapeutic treatment of PAH. PMID:20395700

  13. Molecular pathogenesis of pulmonary arterial hypertension

    PubMed Central

    Rabinovitch, Marlene

    2012-01-01

    Recent clinical and experimental studies are redefining the cellular and molecular bases of pulmonary arterial hypertension (PAH). The genetic abnormalities first identified in association with the idiopathic form of PAH — together with a vast increase in our understanding of cell signaling, cell transformation, and cell-cell interactions; gene expression; microRNA processing; and mitochondrial and ion channel function — have helped explain the abnormal response of vascular cells to injury. Experimental and clinical studies now converge on the intersection and interactions between a genetic predisposition involving the BMPR2 signaling pathway and an impaired metabolic and chronic inflammatory state in the vessel wall. These deranged processes culminate in an exuberant proliferative response that occludes the pulmonary arterial (PA) lumen and obliterates the most distal intraacinar vessels. Here, we describe emerging therapies based on preclinical studies that address these converging pathways. PMID:23202738

  14. Extensive pulmonary sarcoid reaction in a patient with BMPR-2 associated idiopathic pulmonary arterial hypertension.

    PubMed

    Braam, Evelien A J E; Quanjel, Marian J R; Van Haren-Willems, Jolanda H G M; Van Oosterhout, Matthijs F M; Vink, Aryan; Heijdra, Yvonne F; Kwakkel-van Erp, Johanna M

    2016-01-01

    Pulmonary arterial hypertension is a progressive life-threatening disease characterized by vascular remodeling. There is evidence that varied immune mechanism play an important role in progression of pulmonary hypertension.  We describe a case of a 35-year-old woman with idiopathic pulmonary arterial hypertension (IPAH) and a novel BMPR2 mutation, who underwent a successful lung transplantation.  Extensive granulomatous inflammation was seen in the resected lungs. The granulomatous inflammation found in the histology supports  a sarcoid-like reaction due to pulmonary hypertension in the context of the BMPR2 mutation. PMID:27537724

  15. [Arterial hypertension caused by anomaly of the renal artery or its branches in children].

    PubMed

    Broyer, M; Lenoir, G; Guesry, P; Levy-Bentolila, D; Gubler, M C

    1979-11-01

    38 cases of severe hypertension due to a vascular abnormality of the renal pedicle were studied in children under 16 years of age, 18 boys and 20 girls. The most common presentation was at routine clinical examination. The diagnosis of an abnormality of the renal artery was suggested by the appearances of intravenous urography. There were many causes; 4 aneurysms of the renal artery or its branches, 4 fibromuscular dysplasias with one case of bilateral fibromuscular dysplasia, 4 idiopathic stenoses, 2 endarteritis, and 6 thromboses revascularised to variable degrees (2 after umbilical vein catheterisation and one due to DLE). In three cases the hypertension was related to compression of the pedicle by a tumour of haematome, and 14 cases had multiple arterial lesion. In the latter group, 6 cases of neurofibromatosis, 2 cases of William and Beuren's disease, 1 case of generalised Elastorhexia, 2 cases of aortic medio stenosis, probably Takayashu's disease, and 3 unidentified conditions. Surgery was performed on 29 patients, 21 of whom had unilateral lesions and were definitively cured of hypertension. Of the 8 cases with multiple lesions, only 2 were completely corrected with cure of their hypertension. PMID:119510

  16. Coronary artery calcium in hypertension: a review.

    PubMed

    Mallikethi-Reddy, Sagar; Rubenfire, Melvyn; Jackson, Lisa A; Brook, Robert D

    2015-12-01

    Coronary artery calcium (CAC) is a powerful independent predictor of future cardiovascular events. However, the clinical utility of calcium score testing specifically among patients with hypertension is not well defined. We performed a review of studies involving both high blood pressure (BP) and CAC to assess several aspects of the interrelationship. Among four specific topics evaluated, the main objective was to assess the independent association of CAC with cardiovascular risk among patients with hypertension. From 6822 identified publications, 21 studies met criteria for inclusion. All studies (n = 14) that reported the relationship between BP values and the presence or extent of coronary calcium found positive associations. The results from two studies linking coronary calcium with the risk for developing hypertension were mixed. Each of the five studies that evaluated the relationships between CAC score in regard to future cardiovascular events and/or all-cause mortality in patients with high BP reported independent positive associations. The inclusion of calcium score results into prediction models improved risk stratification when statistically evaluated. The findings of this review demonstrate that CAC testing is likely to be of clinical utility for tailoring the medical management of patients with high BP, particularly among individuals with mild or prehypertension. Future trials testing the clinical effectiveness of a calcium score-based treatment algorithm should be considered. PMID:26489731

  17. Changes in large pulmonary arterial viscoelasticity in chronic pulmonary hypertension.

    PubMed

    Wang, Zhijie; Lakes, Roderic S; Golob, Mark; Eickhoff, Jens C; Chesler, Naomi C

    2013-01-01

    Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01-20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation. PMID:24223157

  18. Changes in Large Pulmonary Arterial Viscoelasticity in Chronic Pulmonary Hypertension

    PubMed Central

    Wang, Zhijie; Lakes, Roderic S.; Golob, Mark; Eickhoff, Jens C.; Chesler, Naomi C.

    2013-01-01

    Conduit pulmonary artery (PA) stiffening is characteristic of pulmonary arterial hypertension (PAH) and is an excellent predictor of mortality due to right ventricular (RV) overload. To better understand the impact of conduit PA stiffening on RV afterload, it is critical to examine the arterial viscoelastic properties, which require measurements of elasticity (energy storage behavior) and viscosity (energy dissipation behavior). Here we hypothesize that PAH leads to frequency-dependent changes in arterial stiffness (related to elasticity) and damping ratio (related to viscosity) in large PAs. To test our hypothesis, PAH was induced by the combination of chronic hypoxia and an antiangiogenic compound (SU5416) treatment in mice. Static and sinusoidal pressure-inflation tests were performed on isolated conduit PAs at various frequencies (0.01–20 Hz) to obtain the mechanical properties in the absence of smooth muscle contraction. Static mechanical tests showed significant stiffening of large PAs with PAH, as expected. In dynamic mechanical tests, structural stiffness (κ) increased and damping ratio (D) decreased at a physiologically relevant frequency (10 Hz) in hypertensive PAs. The dynamic elastic modulus (E), a material stiffness, did not increase significantly with PAH. All dynamic mechanical properties were strong functions of frequency. In particular, κ, E and D increased with increasing frequency in control PAs. While this behavior remained for D in hypertensive PAs, it reversed for κ and E. Since these novel dynamic mechanical property changes were found in the absence of changes in smooth muscle cell content or contraction, changes in collagen and proteoglycans and their interactions are likely critical to arterial viscoelasticity in a way that has not been previously described. The impact of these changes in PA viscoelasticity on RV afterload in PAH awaits further investigation. PMID:24223157

  19. Mitochondrial Dynamics in Pulmonary Arterial Hypertension

    PubMed Central

    Ryan, John; Dasgupta, Asish; Huston, Jessica; Chen, Kuang-Huieh; Archer, Stephen L.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is an idiopathic cardiopulmonary disease characterized by obstruction of small pulmonary arteries by excessive proliferation and apoptosis-resistance of vascular cells, as well as inflammation, thrombosis and vasoconstriction. Vascular obstruction increases the afterload faced by the right ventricle (RV), leading to RV failure. The proliferative, obstructive vasculopathy of PAH shares several mitochondrial abnormalities with cancer, notably a shift to aerobic glycolysis and mitochondrial fragmentation. Mitochondria in the pulmonary artery smooth muscle cell (PASMC) normally serve as oxygen sensors. In PAH, acquired mitochondrial abnormalities, including epigenetic silencing of superoxide dismutase (SOD2), disrupt oxygen sensing creating a pseudo-hypoxic environment characterized by normoxic activation of Hypoxia-Inducible Factor-1α (HIF-1α). The resulting metabolic shift to aerobic glycolysis (the Warburg phenomenon) reflects inhibition of pyruvate dehydrogenase by pyruvate dehydrogenase kinases. In addition, altered mitochondrial dynamics result in mitochondrial fragmentation. The molecular basis of this structural change includes upregulation and activation of fission mediators, notably dynamin-related protein 1 (DRP-1), and downregulation of fusion mediators, especially mitofusin-2 (MFN2). These pathogenic mitochondrial abnormalities offer new therapeutic targets. Inhibition of mitotic fission or enhancement of fusion in PAH PASMC slows cell proliferation, causes cell cycle arrest, and induces apoptosis. DRP-1 inhibition or MFN2 gene therapy can regress PAH in experimental models of PAH. This review focuses on the etiology of mitochondrial fragmentation in PAH and explores the therapeutic implications of mitochondrial dynamics in the pulmonary vasculature and RV. PMID:25672499

  20. Arterial Hypertension Aggravates Innate Immune Responses after Experimental Stroke.

    PubMed

    Möller, Karoline; Pösel, Claudia; Kranz, Alexander; Schulz, Isabell; Scheibe, Johanna; Didwischus, Nadine; Boltze, Johannes; Weise, Gesa; Wagner, Daniel-Christoph

    2015-01-01

    Arterial hypertension is not only the leading risk factor for stroke, but also attributes to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood-brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were subjected to photothrombotic stroke. One and 3 days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines along with the post-stroke inflammatory response were analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains 4 days after stroke. Although comparable at day 1, lesion volumes were significantly larger in SHR at day 3. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and P-selectin (CD62P) was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte-leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may finally be responsible for

  1. Arterial Hypertension Aggravates Innate Immune Responses after Experimental Stroke

    PubMed Central

    Möller, Karoline; Pösel, Claudia; Kranz, Alexander; Schulz, Isabell; Scheibe, Johanna; Didwischus, Nadine; Boltze, Johannes; Weise, Gesa; Wagner, Daniel-Christoph

    2015-01-01

    Arterial hypertension is not only the leading risk factor for stroke, but also attributes to impaired recovery and poor outcome. The latter could be explained by hypertensive vascular remodeling that aggravates perfusion deficits and blood–brain barrier disruption. However, besides vascular changes, one could hypothesize that activation of the immune system due to pre-existing hypertension may negatively influence post-stroke inflammation and thus stroke outcome. To test this hypothesis, male adult spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs) were subjected to photothrombotic stroke. One and 3 days after stroke, infarct volume and functional deficits were evaluated by magnetic resonance imaging and behavioral tests. Expression levels of adhesion molecules and chemokines along with the post-stroke inflammatory response were analyzed by flow cytometry, quantitative real-time PCR and immunohistochemistry in rat brains 4 days after stroke. Although comparable at day 1, lesion volumes were significantly larger in SHR at day 3. The infarct volume showed a strong correlation with the amount of CD45 highly positive leukocytes present in the ischemic hemispheres. Functional deficits were comparable between SHR and WKY. Brain endothelial expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and P-selectin (CD62P) was neither increased by hypertension nor by stroke. However, in SHR, brain infiltrating myeloid leukocytes showed significantly higher surface expression of ICAM-1 which may augment leukocyte transmigration by leukocyte–leukocyte interactions. The expression of chemokines that primarily attract monocytes and granulocytes was significantly increased by stroke and, furthermore, by hypertension. Accordingly, ischemic hemispheres of SHR contain considerably higher numbers of monocytes, macrophages and granulocytes. Exacerbated brain inflammation in SHR may finally be responsible for

  2. Berry splenic artery aneurysm rupture in association with segmental arterial mediolysis and portal hypertension.

    PubMed

    Imai, Miwa Akasofu; Kawahara, Ei; Katsuda, Shogo; Yamashita, Tatsuya

    2005-05-01

    A rare case of berry splenic artery aneurysm (SAA) rupture associated with segmental arterial mediolysis (SAM) and portal hypertension is reported. A 66-year-old woman, diagnosed as having liver cirrhosis and portal hypertension 6 years earlier, suddenly developed a lancinating pain in the upper abdomen and lost consciousness. She recovered consciousness while being transferred to hospital by ambulance. During the investigations, her level of consciousness suddenly deteriorated. Ultrasonography showed a massive intraperitoneal hemorrhage, and she died 5(1/2) h after admission. On gross examination at autopsy it was not possible to find the rupture point of the vessel because the pancreas was embedded in a massive hematoma. However, careful dissection of the pancreatic tail after fixation revealed a berry aneurysm measuring 0.8 cm in diameter in a branch adjacent to the bifurcation in the distal third of the main splenic artery. Microscopic examination detected a rupture of the aneurysm. The histology of the arterial wall proximal to the aneurysm showed typical SAM. In general, berry SAA caused by SAM is rare and unlikely to rupture. The SAA in the present case likely occurred and ruptured due to the combination of SAM and portal hypertension. PMID:15871728

  3. Hypertension and arterial stiffness in heart transplantation patients

    PubMed Central

    de Souza-Neto, João David; de Oliveira, Ítalo Martins; Lima-Rocha, Hermano Alexandre; Oliveira-Lima, José Wellington; Bacal, Fernando

    2016-01-01

    OBJECTIVES: Post-transplantation hypertension is prevalent and is associated with increased cardiovascular morbidity and subsequent graft dysfunction. The present study aimed to identify the factors associated with arterial stiffness as measured by the ambulatory arterial stiffness index. METHODS: The current study used a prospective, observational, analytical design to evaluate a group of adult heart transplantation patients. Arterial stiffness was obtained by monitoring ambulatory blood pressure and using the ambulatory arterial stiffness index as the surrogate outcome. Multivariate logistic regression analyses were performed to control confounding. RESULTS: In a group of 85 adult heart transplantation patients, hypertension was independently associated with arterial stiffness (OR 4.98, CI 95% 1.06-23.4) as well as systolic and diastolic blood pressure averages and nighttime descent. CONCLUSIONS: Measurement of ambulatory arterial stiffness index is a new, non-invasive method that is easy to perform, may contribute to better defining arterial stiffness prognosis and is associated with hypertension.

  4. Sildenafil in pediatric pulmonary arterial hypertension

    PubMed Central

    Dhariwal, AK; Bavdekar, SB

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease of varied etiologies. Although PAH has no curative treatment, a greater understanding of pathophysiology, technological advances resulting in early diagnosis, and the availability of several newer drugs have improved the outlook for patients with PAH. Sildenafil is one of the therapeutic agents used extensively in the treatment of PAH in children, as an off-label drug. In 2012, the United States Food and Drug Administration (USFDA) issued a warning regarding the of use high-dose sildenafil in children with PAH. This has led to a peculiar situation where there is a paucity of approved therapies for the management of PAH in children and the use of the most extensively used drug being discouraged by the regulator. This article provides a review of the use of sildenafil in the treatment of PAH in children. PMID:26119438

  5. Pulmonary arterial hypertension in connective tissue diseases.

    PubMed

    Goldberg, Avram

    2010-01-01

    Pulmonary arterial hypertension (PAH) is an entity that is known to complicate connective tissue diseases (CTD). PAH in CTD is a very important diagnosis which greatly affects treatment and prognosis. The most commonly affected CTD is scleroderma, although lupus, inflammatory myopathies such as poly and dermatomyositis, and mixed CTD are also associated with PAH. The manifestations of PAH have both similarities and differences when occurring in the setting of CTD as compared with idiopathic PAH. These differences are most notable in scleroderma. In this section we will discuss the features of PAH as they appear in CTDs, and in particular, scleroderma. The focus of this article is an approach to the diagnosis and treatment of PAH in CTD, and how this setting might differ from idiopathic and other forms of PAH. PMID:20160534

  6. [Pulmonary arterial hypertension: changing approaches to management].

    PubMed

    Sidorenko, B A; Preobrazhenskiĭ, D V; Batyraliev, T A; Belenkov, Iu N

    2011-01-01

    The review is devoted to different aspects of pulmonary arterial hypertension (PAH); new classification of PAH is published in 2010. There are idiopathic PAH and PAH associated with other diseases. Current guidelines recommend to treat PAH only after the verification of diagnosis with right heart catheterization and acute tests with vasodilators. Patients-reactors should be treated with calcium antagonists. The following drugs related to one of three categories should be used in PAH: (1) prostanoids (epoprostenol, iloprost et al.); (2) blockers of endothelin receptors (bosentan, ambrisentan, sitaxsentan); (3) phosphodiesterase 5 type inhibitors (sildenafil, tadalafil et al.) In majority of cases the combined treatment is used, usually the combination of bosentan and sildenafil is used. PMID:21626809

  7. Endothelin receptor antagonists in pulmonary arterial hypertension.

    PubMed

    Channick, Richard N; Sitbon, Olivier; Barst, Robyn J; Manes, Alessandra; Rubin, Lewis J

    2004-06-16

    Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension (PAH). Laboratory and clinical investigations have clearly shown that endothelin (ET)-1 is overexpressed in several forms of pulmonary vascular disease and likely plays a significant pathogenetic role in the development and progression of pulmonary vasculopathy. Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials. In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil. The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation. PMID:15194180

  8. Exercise intolerance in pulmonary arterial hypertension.

    PubMed

    Fowler, Robin M; Gain, Kevin R; Gabbay, Eli

    2012-01-01

    Pulmonary arterial hypertension (PAH) is associated with symptoms of dyspnea and fatigue, which contribute to exercise limitation. The origins and significance of dyspnea and fatigue in PAH are not completely understood. This has created uncertainly among healthcare professionals regarding acceptable levels of these symptoms, on exertion, for patients with PAH. Dysfunction of the right ventricle (RV) contributes to functional limitation and mortality in PAH; however, the role of the RV in eliciting dyspnea and fatigue has not been thoroughly examined. This paper explores the contribution of the RV and systemic and peripheral abnormalities to exercise limitation and symptoms in PAH. Further, it explores the relationship between exercise abnormalities and symptoms, the utility of the cardiopulmonary exercise test in identifying RV dysfunction, and offers suggestions for further research. PMID:22737582

  9. Exercise Intolerance in Pulmonary Arterial Hypertension

    PubMed Central

    Fowler, Robin M.; Gain, Kevin R.; Gabbay, Eli

    2012-01-01

    Pulmonary arterial hypertension (PAH) is associated with symptoms of dyspnea and fatigue, which contribute to exercise limitation. The origins and significance of dyspnea and fatigue in PAH are not completely understood. This has created uncertainly among healthcare professionals regarding acceptable levels of these symptoms, on exertion, for patients with PAH. Dysfunction of the right ventricle (RV) contributes to functional limitation and mortality in PAH; however, the role of the RV in eliciting dyspnea and fatigue has not been thoroughly examined. This paper explores the contribution of the RV and systemic and peripheral abnormalities to exercise limitation and symptoms in PAH. Further, it explores the relationship between exercise abnormalities and symptoms, the utility of the cardiopulmonary exercise test in identifying RV dysfunction, and offers suggestions for further research. PMID:22737582

  10. Arterial pulmonary hypertension in noncardiac intensive care unit

    PubMed Central

    Tsapenko, Mykola V; Tsapenko, Arseniy V; Comfere, Thomas BO; Mour, Girish K; Mankad, Sunil V; Gajic, Ognjen

    2008-01-01

    Pulmonary artery pressure elevation complicates the course of many complex disorders treated in a noncardiac intensive care unit. Acute pulmonary hypertension, however, remains underdiagnosed and its treatment frequently begins only after serious complications have developed. Significant pathophysiologic differences between acute and chronic pulmonary hypertension make current classification and treatment recommendations for chronic pulmonary hypertension barely applicable to acute pulmonary hypertension. In order to clarify the terminology of acute pulmonary hypertension and distinguish it from chronic pulmonary hypertension, we provide a classification of acute pulmonary hypertension according to underlying pathophysiologic mechanisms, clinical features, natural history, and response to treatment. Based on available data, therapy of acute arterial pulmonary hypertension should generally be aimed at acutely relieving right ventricular (RV) pressure overload and preventing RV dysfunction. Cases of severe acute pulmonary hypertension complicated by RV failure and systemic arterial hypotension are real clinical challenges requiring tight hemodynamic monitoring and aggressive treatment including combinations of pulmonary vasodilators, inotropic agents and systemic arterial vasoconstrictors. The choice of vasopressor and inotropes in patients with acute pulmonary hypertension should take into consideration their effects on vascular resistance and cardiac output when used alone or in combinations with other agents, and must be individualized based on patient response. PMID:19183752

  11. Right Ventricular Dysfunction in Systemic Sclerosis Associated Pulmonary Arterial Hypertension

    PubMed Central

    Tedford, Ryan J.; Mudd, James O.; Girgis, Reda E.; Mathai, Stephen C.; Zaiman, Ari L.; Housten-Harris, Traci; Boyce, Danielle; Kelemen, Benjamin W.; Bacher, Anita C.; Shah, Ami A.; Hummers, Laura K.; Wigley, Fredrick M.; Russell, Stuart D.; Saggar, Rajeev; Saggar, Rajan; Maughan, W. Lowell; Hassoun, Paul M.; Kass, David A.

    2013-01-01

    Background Systemic sclerosis associated pulmonary artery hypertension (SScPAH) has a worse prognosis compared to idiopathic pulmonary arterial hypertension (IPAH), with a median survival of 3 years after diagnosis often due to right ventricular (RV) failure. We tested if SScPAH or systemic sclerosis related pulmonary hypertension with interstitial lung disease (SSc-ILD-PH) imposes a greater pulmonary vascular load than IPAH and/or leads to worse RV contractile function. Methods and Results We analyzed pulmonary artery pressures and mean flow in 282 patients with pulmonary hypertension (166 SScPAH, 49 SSc-ILD-PH, 67 IPAH). An inverse relation between pulmonary resistance (RPA) and compliance (CPA) was similar for all three groups, with a near constant resistance × compliance product. RV pressure-volume loops were measured in a subset, IPAH (n=5) and SScPAH (n=7) as well as SSc without PH (SSc-no-PH, n=7) to derive contractile indexes (end-systolic elastance [Ees] and preload recruitable stroke work [Msw]), measures of right ventricular load (arterial elastance [Ea]), and RV-pulmonary artery coupling (Ees/Ea). RV afterload was similar in SScPAH and IPAH (RPA=7.0±4.5 vs. 7.9±4.3 Wood units; Ea=0.9±0.4 vs. 1.2±0.5 mmHg/mL; CPA=2.4±1.5 vs. 1.7±1.1 mL/mmHg; p>0.3 for each). Though SScPAH did not have greater vascular stiffening compared to IPAH, RV contractility was more depressed (Ees=0.8±0.3 vs. 2.3±1.1, p<0.01; Msw=21±11 vs. 45±16, p=0.01), with differential RV-PA uncoupling (Ees/Ea=1.0±0.5 vs. 2.1±1.0, p=.03). This ratio was higher in SSc-no-PH (Ees/Ea = 2.3±1.2, p=0.02 vs. SScPAH). Conclusions RV dysfunction is worse in SScPAH compared to IPAH at similar afterload, and may be due to intrinsic systolic function rather than enhanced pulmonary vascular resistive and/or pulsatile loading. PMID:23797369

  12. [Emerging therapies for the treatment of pulmonary arterial hypertension].

    PubMed

    Ghofrani, Hossein Ardeschir; Voswinckel, Robert; Reichenberger, Frank; Grimminger, Friedrich; Seeger, Werner

    2005-06-01

    Besides all progress in the therapy of pulmonary arterial hypertension over the past years, there is still no cure for this devastating disease. By introducing effective and nonparenteral medications (e. g., oral endothelin receptor antagonists [ERAs], inhaled prostanoids), quality of life, exercise tolerance and prognosis of patients have substantially improved. However, applicability of these therapies can be hampered by serious side effects and/or the necessity for elaborate application techniques. Whether selective ERAs--due to their specificity for the A-type receptor--have potential benefits over the nonselective ERA bosentan remains to be answered by the analysis of pivotal trials recently carried out with ambrisentan and sitaxsentan. Inhaled treprostinil can potentially have benefits over the already approved inhaled iloprost, related to its higher pulmonary selectivity as well as to the longer biological half-life. However, this has yet to be proven in long-term randomized controlled trials. In comparison to the previously mentioned substances, the selective phosphodiesterase-5 (PDE5) inhibitor sildenafil approached approval closest as new therapy for pulmonary arterial hypertension. Oral sildenafil has proven its efficacy as a selective pulmonary vasodilator in various forms of pulmonary hypertension. The results of the pivotal phase III trial have confirmed the strong efficacy and excellent tolerability of this substance. Combination therapies, despite all progress seen for single agents, can be regarded as the most promising therapeutic approach for the future. However, controlled randomized trials that are currently under consideration have to confirm this notion. PMID:15965806

  13. Computational modeling of hypertensive growth in the human carotid artery

    NASA Astrophysics Data System (ADS)

    Sáez, Pablo; Peña, Estefania; Martínez, Miguel Angel; Kuhl, Ellen

    2014-06-01

    Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively.

  14. A Contemporary Approach to Pulmonary Arterial Hypertension.

    PubMed

    Krishnan, Udhay; Horn, Evelyn M

    2016-09-01

    In recent years, there have been major changes in the landscape of pulmonary arterial hypertension therapy with the introduction of novel agents and innovative treatment strategies for this progressive disease. The aim of this review is to discuss the evolution in trial design in this field and highlight the salient features of recently published studies. We also summarize our approach to therapy selection in this chronic disease and identify areas for future exploration. The therapeutic armamentarium now includes 13 approved therapies. While most of these agents have been studied in small, short-term trials using the 6-min walk distance as a primary endpoint, there has been a shift in recent years toward larger, long-term, event-driven trials that utilize combined morbidity and mortality endpoints. The SERAPHIN and GRIPHON trials were two such studies, which led to the approval of the dual endothelin-receptor antagonist macitentan and the selective prostacyclin receptor antagonist selexipag, respectively. Other event-driven trials, like AMBITION and COMPASS-2, have provided valuable insight into the use of combined oral therapies in symptomatic patients. In conclusion, despite being a more manageable disease in the modern treatment era, pulmonary hypertension is still associated with considerable morbidity and much more work remains to be done in this field. Important questions remain about the most optimal way to manage patients and conduct trials going forward. PMID:27491673

  15. Management of a child with pulmonary arterial hypertension presenting with systemic hypertension.

    PubMed

    Flores, Saul; Daily, Joshua; Pratap, Jayant Nick; Cash, Michelle C; Hirsch, Russel

    2016-02-01

    We describe the course and management of a 12-year-old girl with severe pulmonary arterial hypertension who initially presented with severe systemic hypertension. Successful therapy included pulmonary vasodilators and an atrial septostomy, while ensuring adequate maintenance of her systemic vascular resistance to maintain cardiac output. Clear understanding of the physiology and judicious medical management in patients with severe pulmonary arterial hypertension using extreme compensatory mechanisms is vitally important. PMID:26082002

  16. Non-congenital heart disease associated pediatric pulmonary arterial hypertension.

    PubMed

    Ivy, D D; Feinstein, J A; Humpl, T; Rosenzweig, E B

    2009-12-01

    Recognition of causes of pulmonary hypertension other than congenital heart disease is increasing in children. Diagnosis and treatment of any underlying cause of pulmonary hypertension is crucial for optimal management of pulmonary hypertension. This article discusses the available knowledge regarding several disorders associated with pulmonary hypertension in children: idiopathic pulmonary arterial hypertension (IPAH), pulmonary capillary hemangiomatosis, pulmonary veno-occlusive disease, hemoglobinopathies, hepatopulmonary syndrome, portopulmonary hypertension and HIV. Three classes of drugs have been extensively studied for the treatment of IPAH in adults: prostanoids (epoprostenol, treprostinil, iloprost, beraprost), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase inhibitors (Sildenafil, tadalafil). These medications have been used in treatment of children with pulmonary arterial hypertension, although randomized clinical trial data is lacking. As pulmonary vasodilator therapy in certain diseases may be associated with adverse outcomes, further study of these medications is needed before widespread use is encouraged. PMID:21852894

  17. Non-congenital heart disease associated pediatric pulmonary arterial hypertension

    PubMed Central

    Ivy, D. D.; Feinstein, J. A.; Humpl, T.; Rosenzweig, E. B.

    2011-01-01

    Recognition of causes of pulmonary hypertension other than congenital heart disease is increasing in children. Diagnosis and treatment of any underlying cause of pulmonary hypertension is crucial for optimal management of pulmonary hypertension. This article discusses the available knowledge regarding several disorders associated with pulmonary hypertension in children: idiopathic pulmonary arterial hypertension (IPAH), pulmonary capillary hemangiomatosis, pulmonary veno-occlusive disease, hemoglobinopathies, hepatopulmonary syndrome, portopulmonary hypertension and HIV. Three classes of drugs have been extensively studied for the treatment of IPAH in adults: prostanoids (epoprostenol, treprostinil, iloprost, beraprost), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase inhibitors (Sildenafil, tadalafil). These medications have been used in treatment of children with pulmonary arterial hypertension, although randomized clinical trial data is lacking. As pulmonary vasodilator therapy in certain diseases may be associated with adverse outcomes, further study of these medications is needed before widespread use is encouraged. PMID:21852894

  18. Genetics Home Reference: pulmonary arterial hypertension

    MedlinePlus

    ... Primary pulmonary hypertension 2 Primary pulmonary hypertension 3 Primary pulmonary hypertension 4 ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific articles on PubMed (1 link) PubMed OMIM (4 links) ...

  19. Epidemiology and prevention of arterial hypertension in Poland.

    PubMed

    Zdrojewski, Tomasz; Wyrzykowski, Bogdan; Szczech, Radosław; Wierucki, Lukasz; Naruszewicz, Marek; Narkiewicz, Krzysztof; Zarzeczna-Baran, Marzena

    2005-12-01

    The authors review the present situation in epidemiology and prevention of arterial hypertension in Poland. In 2002, the NATPOL PLUS survey on representative sample of adults (n=3051, age range 18-93) was conducted. Prevalence of hypertension, diagnosed on basis of three separate visits, was 29%, awareness 67% and efficacy of treatment 12.5%. Thus, in Poland, one-third of 8.6 million hypertensives are unaware of their disease. A comparison with data from other countries should be careful due to the different methods (age range, number of readings and visits) used in the studies. The data, in concert with a decrease in awareness of one's own blood pressure (from 71% in 1994 to 59% in 2002), called for urgent preventive measures. Two large interventions were implemented under the National Programme POLKARD in 2003: the Polish 400 Cities Project aimed to increase detection and knowledge of hypertension and other risk factors among small-town and village communities, and the educational project, A Chance for the Young Heart targeted at children aged 11-14 years and using traditional teaching methods and an interactive Internet website. Also, an educational and marketing programme targeted at public opinion leaders and decision makers (trade unions, local governments, healthcare financing authorities, print media and radio, the Polish Parliament) started in 1999 and is still in process. PMID:16429636

  20. Recapitulation of developing artery muscularization in pulmonary hypertension.

    PubMed

    Sheikh, Abdul Q; Lighthouse, Janet K; Greif, Daniel M

    2014-03-13

    Excess smooth muscle accumulation is a key component of many vascular disorders, including atherosclerosis, restenosis, and pulmonary artery hypertension, but the underlying cell biological processes are not well defined. In pulmonary artery hypertension, reduced pulmonary artery compliance is a strong independent predictor of mortality, and pathological distal arteriole muscularization contributes to this reduced compliance. We recently demonstrated that embryonic pulmonary artery wall morphogenesis consists of discrete developmentally regulated steps. In contrast, poor understanding of distal arteriole muscularization in pulmonary artery hypertension severely limits existing therapies that aim to dilate the pulmonary vasculature but have modest clinical benefit and do not prevent hypermuscularization. Here, we show that most pathological distal arteriole smooth muscle cells, but not alveolar myofibroblasts, derive from pre-existing smooth muscle. Furthermore, the program of distal arteriole muscularization encompasses smooth muscle cell dedifferentiation, distal migration, proliferation, and then redifferentiation, thereby recapitulating many facets of arterial wall development. PMID:24582963

  1. Atherosclerotic Renal Artery Stenosis and Hypertension: Pragmatism, Pitfalls, and Perspectives.

    PubMed

    Bavishi, Chirag; de Leeuw, Peter W; Messerli, Franz H

    2016-06-01

    For many years and even decades, a diagnostic work-up to look for a secondary form of hypertension, particularly of renovascular origin, has been a central tenet in medicine. Atherosclerotic renal artery stenosis is considered the most common cause of renovascular hypertension. However, advances in understanding the complex pathophysiology of this condition and the recently documented futility of renal revascularization bring into question whether atherosclerotic renal artery stenosis truly causes "renovascular hypertension." From a clinical point of view, a clear distinction should be made between hypertension associated with atherosclerotic renal artery stenosis and hypertension caused by renal artery stenosis-induced activation of the renin-angiotensin-aldosterone system. Most patients with atherosclerotic renal artery stenosis do not have a form of hypertension that is remediable or improved by angioplasty; to expose them to the cost, inconvenience, and risk of a diagnostic work-up add up to little more than a wild goose chase. However, with very few exceptions, medical therapy with antihypertensives and statins remains the cornerstone for the management of patients with atherosclerotic renal artery stenosis and hypertension. PMID:26522797

  2. Long term combination treatment for severe idiopathic pulmonary arterial hypertension

    PubMed Central

    Affuso, Flora; Cirillo, Plinio; Ruvolo, Antonio; Carlomagno, Guido; Fazio, Serafino

    2010-01-01

    We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event. PMID:21160759

  3. [Treatment algorithm for pulmonary arterial hypertension].

    PubMed

    Hoeper, Marius M

    2005-06-01

    During the last decade, we have witnessed substantial improvements in the therapeutic options for pulmonary arterial hypertension (PAH), including true innovations targeting some of the mechanisms involved in the pathogenesis of this devastating disease. Intravenous epoprostenol was the first drug to improve symptoms and survival of patients with PAH. Novel prostanoids including subcutaneous treprostinil and inhaled iloprost also have beneficial effects in many patients, although their long-term efficacy is less well known. Among the newer treatments for PAH, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors have reshaped clinical practice. The endothelin receptor antagonist bosentan has been approved in many parts of the world and most current guidelines recommend this drug as first-line treatment for PAH. Novel endothelin receptor antagonists such as sitaxsentan and ambrisentan are currently being investigated. The phosphodiesterase type 5 inhibitor sildenafil is also being intensively studied in patients with pulmonary hypertension, and most of the available data look promising, although approval for PAH is still pending. Other phosphodiesterase type 5 inhibitors have not yet undergone extensive study in PAH. However, PAH is a complex disorder and targeting a single pathway cannot be expected to be uniformly successful. Thus, combining substances with different modes of action is expected to improve symptoms, hemodynamics and survival in PAH patients, although combination therapy has yet to undergo the scrutiny of large randomized clinical trials.Based on the available data, several guidelines for the diagnostic and therapeutic approach to PAH have been published recently. These guidelines have incorporated treatment algorithms, which, fortunately, are virtually identical. The present review article summarizes the current guidelines to the management of patients with PAH. PMID:15965810

  4. Pseudo-hypertension and arterial stiffness: a review.

    PubMed

    Foran, Timothy G; Sheahan, Noirin F; Cunningham, Conal; Feely, John

    2004-04-01

    Hypertension is a condition of persistently elevated blood pressure, associated with increased cardiovascular risk. Non-invasive BP measurement using Korotkoff sounds is the most common method of screening for the condition. The possibility of inaccurate readings leading to a false diagnosis of hypertension (pseudo-hypertension) is of concern. Stiffened arteries in the elderly have been proposed as being the primary cause of pseudo-hypertension. Non-invasive detection of pseudo-hypertension remains problematic. This paper reviews clinical literature on pseudo hypertension and approaches to measuring the compressive stiffness of arteries, as well as biomechanical literature regarding models of arterial stiffness and the origin of Korotkoff sounds. Models of the latter show the importance of the relationship between transmural pressure and cross-sectional area (P1/Csa curve) of the brachial artery as it closes under the influence of the pressure cuff. The review concludes that future research on pseudo-hypertension should include development of new instrumentation to measure the P1/Csa curve of the brachial artery in vivo using non-invasive techniques suitable for application to an elderly population. PMID:15132306

  5. Breath Analysis in Pulmonary Arterial Hypertension

    PubMed Central

    Cikach, Frank S.; Tonelli, Adriano R.; Barnes, Jarrod; Paschke, Kelly; Newman, Jennie; Grove, David; Dababneh, Luma; Wang, Sihe

    2014-01-01

    Background: Pulmonary arterial hypertension (PAH) is a progressive and devastating condition characterized by vascular cell proliferation and is associated with several metabolic derangements. We hypothesized that metabolic derangements in PAH can be detected by measuring metabolic by-products in exhaled breath. Methods: We collected breath and blood samples from patients with PAH at the time of right-sided heart catheterization (n = 31) and from healthy control subjects (n = 34). Breath was analyzed by selected ion flow tube-mass spectrometry in predetermined training and validation cohorts. Results: Patients with PAH were 51.5 ± 14 years old, and 27 were women (85%). Control subjects were 38 ± 13 years old, and 22 were women (65%). Discriminant analysis in the training set identified three ion peaks (H3O+29+, NO+56+, and O2+98+) and the variable age that correctly classified 88.9% of the individuals. In an independent validation cohort, 82.8% of the individuals were classified correctly. The concentrations of the volatile organic compounds 2-propanol, acetaldehyde, ammonia, ethanol, pentane, 1-decene, 1-octene, and 2-nonene were different in patients with PAH compared with control subjects. Exhaled ammonia was higher in patients with PAH (median [interquartile range]: 94.7 parts per billion (ppb) [70-129 ppb] vs 60.9 ppb [46-77 ppb], P < .001) and was associated with right atrial pressure (ρ = 0.57, P < .001), mean pulmonary artery pressure (ρ = 0.43, P = .015), cardiac index by thermodilution (ρ = −0.39, P = .03), pulmonary vascular resistance (ρ = 0.40, P = .04), mixed venous oxygen (ρ = −0.59, P < .001), and right ventricular dilation (ρ = 0.42, P = .03). Conclusions: Breathprint is different between patients with PAH and healthy control subjects. Several specific compounds, including ammonia, were elevated in the breath of patients with PAH. Exhaled ammonia levels correlated with severity of disease. PMID:24091389

  6. Hypertrophy and hyperplasia of smooth muscle cells of small intramyocardial arteries in spontaneously hypertensive rats.

    PubMed

    Amann, K; Gharehbaghi, H; Stephen, S; Mall, G

    1995-01-01

    Hearts of stroke-prone spontaneously hypertensive rats (SHR) were investigated by means of stereology and were compared with those of normotensive. Wistar-Kyoto controls. At the age of 9 months, hypertensive rats showed cardiac hypertrophy, marked myocardial fibrosis, activation of nonvascular interstitium, focal myocytial degeneration, reduction of capillarization, and microarteriopathy of small intramyocardial arteries. Stereologically, a significant increase in the total left ventricular arterial wall volume (+180% versus controls) was found in SHR hearts. By using new stereological techniques, the orientator and the nucleator, we investigated whether this significant increase in total left ventricular arterial wall volume was due to hyperplasia of smooth muscle cells in addition to the process of vascular smooth muscle cell hypertrophy that is common in SHR. Additionally, the nuclear size and ratio of cell volume to nuclear volume were determined using another new stereological technique, the selector. The stereological data indicate a significant increase in mean cell and nuclear volumes as well as in the total number of left ventricular arterial smooth muscle cells of SHR. Additionally, the total length of intramyocardial arteries was also significantly increased in hypertensive rats. The volume and number of arterial smooth muscle cells per arterial length were significantly (P < .001 and P < .05, respectively) higher in SHR than in normotensive controls. Thus, we conclude that hypertrophy and hyperplasia of smooth muscle cells are involved in intramyocardial arterial growth processes in hypertensive heart remodeling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7843743

  7. Management of Pulmonary Arterial Hypertension During Pregnancy

    PubMed Central

    Thomas, Shibu; Safdar, Zeenat; Torres, Fernando; Pacheco, Luis D.; Feldman, Jeremy; deBoisblanc, Bennet

    2013-01-01

    Background: Pulmonary arterial hypertension (PAH) is a rare disease with a predilection for young women that is associated with right ventricular failure and premature death. PAH can complicate pregnancy with hemodynamic instability or sudden death during parturition and postpartum. Our aim was to examine the impact of PAH on pregnancy outcomes in the modern era. Methods: We conducted a retrospective evaluation of pregnant patients with PAH managed between 1999 and 2009 at five US medical centers. Patient demographics, medical therapies, hemodynamic measurements, manner of delivery, anesthetic administration, and outcomes were assessed. Results: Among 18 patients with PAH, 12 continued pregnancy and six underwent pregnancy termination. Right ventricular systolic pressure in patients managed to parturition was 82 ± 5 mm Hg and in patients with pregnancy termination was 90 ± 16 mm Hg. Six patients underwent pregnancy termination at mean gestational age of 13 ± 1.0 weeks with no maternal deaths or complications. Twelve patients elected to continue their pregnancy and were hospitalized at 29 ± 1.4 weeks. PAH-specific therapy was administered to nine (75%) at time of delivery consisting of sildenafil, IV prostanoids, or combination therapy. All parturients underwent Cesarean section at 34 weeks with one in-hospital death and one additional death 2 months postpartum for maternal mortality of 16.7%. Conclusions: Compared with earlier reports, maternal morbidity and mortality among pregnant women with PAH was reduced, yet maternal complications remain significant and patients should continue to be counseled to avoid pregnancy. PMID:23100080

  8. Updated treatment algorithm of pulmonary arterial hypertension.

    PubMed

    Galiè, Nazzareno; Corris, Paul A; Frost, Adaani; Girgis, Reda E; Granton, John; Jing, Zhi Cheng; Klepetko, Walter; McGoon, Michael D; McLaughlin, Vallerie V; Preston, Ioana R; Rubin, Lewis J; Sandoval, Julio; Seeger, Werner; Keogh, Anne

    2013-12-24

    The demands on a pulmonary arterial hypertension (PAH) treatment algorithm are multiple and in some ways conflicting. The treatment algorithm usually includes different types of recommendations with varying degrees of scientific evidence. In addition, the algorithm is required to be comprehensive but not too complex, informative yet simple and straightforward. The type of information in the treatment algorithm are heterogeneous including clinical, hemodynamic, medical, interventional, pharmacological and regulatory recommendations. Stakeholders (or users) including physicians from various specialties and with variable expertise in PAH, nurses, patients and patients' associations, healthcare providers, regulatory agencies and industry are often interested in the PAH treatment algorithm for different reasons. These are the considerable challenges faced when proposing appropriate updates to the current evidence-based treatment algorithm.The current treatment algorithm may be divided into 3 main areas: 1) general measures, supportive therapy, referral strategy, acute vasoreactivity testing and chronic treatment with calcium channel blockers; 2) initial therapy with approved PAH drugs; and 3) clinical response to the initial therapy, combination therapy, balloon atrial septostomy, and lung transplantation. All three sections will be revisited highlighting information newly available in the past 5 years and proposing updates where appropriate. The European Society of Cardiology grades of recommendation and levels of evidence will be adopted to rank the proposed treatments. PMID:24355643

  9. Endothelin receptor antagonists in pulmonary arterial hypertension.

    PubMed

    Dupuis, J; Hoeper, M M

    2008-02-01

    The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients. PMID:18238950

  10. CD133+ cells in pulmonary arterial hypertension.

    PubMed

    Foris, Vasile; Kovacs, Gabor; Marsh, Leigh M; Bálint, Zoltán; Tötsch, Martin; Avian, Alexander; Douschan, Philipp; Ghanim, Bahil; Klepetko, Walter; Olschewski, Andrea; Olschewski, Horst

    2016-08-01

    Circulating mononuclear cells may play an important role for the vascular remodelling in pulmonary arterial hypertension (PAH), but studies addressing multiple progenitor populations are rare and inconsistent.We used a comprehensive fluorescence-activated cell sorting analysis of circulating mononuclear cells in 20 PAH patients and 20 age- and sex-matched controls, and additionally analysed CD133(+) cells in the lung tissue of five PAH transplant recipients and five healthy controls (donor lungs).PAH patients were characterised by increased numbers of circulating CD133(+) cells and lymphopenia as compared with control. In PAH, CD133(+) subpopulations positive for CD117 or CD45 were significantly increased, whereas CD133(+)CD309(+), CD133(+)CXCR2(+) and CD133(+)CD31(+) cells were decreased. In CD133(+) cells, SOX2, Nanog, Ki67 and CXCR4 were not detected, but Oct3/4 mRNA was present in both PAH and controls. In the lung tissue, CD133(+) cells included three main populations: type 2 pneumocytes, monocytes and undifferentiated cells without significant differences between PAH and controls.In conclusion, circulating CD133(+) progenitor cells are elevated in PAH and consist of phenotypically different subpopulations that may be up- or downregulated. This may explain the inconsistent results in the literature. CD133(+) type 2 pneumocytes in the lung tissue are not associated with circulating CD133(+) mononuclear cells. PMID:27103380

  11. [Arterial hypertension in special situations: mild, systolic and in pregnancy].

    PubMed

    Luque Otero, M; Fernández Pinilla, C

    1990-01-01

    Mild hypertension is very common, 50% of hypertensives being with their diastolic BP between 90 and 104 mmHg. Many large studies, especially HDFP, had shown not only the deleterious cardiovascular effects of mild hypertension but also the benefits obtained with the therapy. The non-pharmacological approach should be the first step in the treatment of mild hypertension. Isolated systolic hypertension have a high prevalence in the elderly, increasing the cardiovascular morbidity and mortality. Sodium restriction and, if necessary, vasodilators increasing the arterial compliance seem to be the logical approach to treat isolated systolic hypertension. Finally, eclampsia is the most serious complication of pregnancy - induced hypertension. The treatment with bed rest and either betablockers or methyldopa is beneficial. If eclampsia occurs hydralazine, magnesium sulphate or nifedipine should be used. PMID:2186454

  12. Effects of portal hypertension on responsiveness of rat mesenteric artery and aorta.

    PubMed Central

    Cawley, T; Geraghty, J; Osborne, H; Docherty, J R

    1995-01-01

    1. We have examined the effects of pre-hepatic portal hypertension on the responsiveness of rat small mesenteric arteries and aorta. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham-operated. 2. In rat mesenteric arteries, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of noradrenaline (NA), but the maximum contractile responses to NA, U46619 and KCl were significantly increased in vessels from portal hypertensive animals. This altered maximum contractile response was not due to alterations in smooth muscle mass. 3. In rat mesenteric arteries, there were no significant differences between portal hypertensive and sham-operated animals in endothelium-dependent relaxations to acetylcholine (ACh). The difference between portal hypertensive and sham-operated rats in the maximum response to U46619 was maintained following a combination of methylene blue (1 microM) and NG-monomethyl-L-arginine (100 microM), suggesting that any differences in endothelial function do not explain differences in the response to vasoconstrictors. 4. In rat aorta, there were no significant differences between portal hypertensive and sham-operated animals in the contractile response to NA or KCl or in the endothelium-dependent relaxations to ACh. 5. In pithed rats, there was no difference between portal hypertensive and sham-operated animals in the pressor potency of NA. 6. It is concluded that portal hypertension produces an increase in the contractile response to the vasoconstrictors NA, U46619 and KCl in rat mesenteric arteries but not in the aorta. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle. PMID:7773539

  13. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension.

    PubMed

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed; Erzurum, Serpil C; Aldred, Micheala A

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa. PMID:27224443

  14. Mitochondrial Haplogroups and Risk of Pulmonary Arterial Hypertension

    PubMed Central

    Farha, Samar; Hu, Bo; Comhair, Suzy; Zein, Joe; Dweik, Raed

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a serious and often fatal disease. It is a panvasculopathy of the pulmonary microcirculation characterized by vasoconstriction and arterial obstruction due to vascular proliferation and remodeling and ultimately right ventricular failure. Mitochondrial dysfunction is a universal finding in pulmonary vascular cells of patients with PAH, and is mechanistically linked to disease origins in animal models of pulmonary hypertension. Mitochondria have their own circular DNA (mtDNA), which can be subgrouped into polymorphic haplogroup variants, some of which have been identified as at-risk or protective from cardiovascular and/or neurodegenerative diseases. Here, we hypothesized that mitochondrial haplogroups may be associated with PAH. To test this, mitochondrial haplogroups were determined in a cohort of PAH patients and controls [N = 204 Caucasians (125 PAH and 79 controls) and N = 46 African Americans (13 PAH and 33 controls)]. Haplogroup L was associated with a lower rate of PAH as compared to macrohaplogroups N and M. When haplogroups were nested based on ancestral inheritance and controlled for age, gender and race, haplogroups M and HV, JT and UK of the N macro-haplogroup had significantly higher rates of PAH compared to the ancestral L (L0/1/2 and L3) (all p ≤ 0.05). Overall, the findings suggest that mitochondrial haplogroups influence risk of PAH and that a vulnerability to PAH may have emerged under the selective enrichment of specific haplogroups that occurred with the migration of populations out of Africa. PMID:27224443

  15. Pulmonary hypertension

    MedlinePlus

    Pulmonary arterial hypertension; Sporadic primary pulmonary hypertension; Familial primary pulmonary hypertension; Idiopathic pulmonary arterial hypertension; Primary pulmonary hypertension; PPH; Secondary pulmonary ...

  16. Altered agonist-activated sup 86 Rb+ efflux from arteries in canine renal hypertension

    SciTech Connect

    Cox, R.H.; Bagshaw, R.J. )

    1989-07-01

    Basal rate constants for {sup 86}Rb+ efflux from renal arteries of renal hypertensive dogs were lower than those of control animals whereas no differences were found for coronary arteries. Norepinephrine produced parallel increases in efflux rate constants for hypertensive and control renal arteries, but serotonin produced smaller responses in hypertensive compared to control coronary arteries.

  17. Arginine metabolic endotypes in pulmonary arterial hypertension

    PubMed Central

    Wedes, Samuel H.; Hsu, Jean W.; Bohren, Kurt M.; Comhair, Suzy A. A.; Jahoor, Farook; Erzurum, Serpil C.

    2015-01-01

    Abstract Decreased synthesis of nitric oxide (NO) by NO synthases (NOS) is believed to play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). Multiple factors may contribute to decreased NO bioavailability, including increased activity of arginase, the enzyme that converts arginine to ornithine and urea, which may compete with NOS for arginine; inadequate de novo arginine production from citrulline; and increased concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NOS. We hypothesized that PAH patients with the lowest arginine availability secondary to increased arginase activity and/or inadequate de novo arginine synthesis might have a slower rate of NO synthesis and greater pulmonary vascular resistance. Nine patients with group 1 PAH and 10 healthy controls were given primed, constant intravenous infusions of 15N2-arginine, 13C,2H4-citrulline, 15N2-ornithine, and 13C-urea in the postabsorptive state. The results showed that, compared with healthy controls, PAH patients had a tendency toward increased arginine clearance and ornithine flux but no difference in arginine and citrulline flux, de novo arginine synthesis, or NO synthesis. Arginine-to-ADMA ratio was increased in PAH patients. Two endotypes of patients with low and high arginase activity were identified; compared with the low-arginase group, the patients with high arginase had increased arginine flux, slower NO synthesis, and lower plasma concentrations of ADMA. These results demonstrate that increased breakdown of arginine by arginase occurs in PAH and affects NO synthesis. Furthermore, there is no compensatory increase in de novo arginine synthesis to overcome this increased utilization of arginine by arginase. PMID:25992277

  18. Current Clinical Management of Pulmonary Arterial Hypertension

    PubMed Central

    Sung, Yon K; Perez, Vinicio de Jesus; Liu, Juliana; Spiekerkoetter, Edda

    2014-01-01

    Over the last 2 decades there has been a tremendous evolution in the evaluation and care of patients with pulmonary arterial hypertension (PAH). The introduction of targeted PAH therapy consisting of prostacyclin and its analogues, endothelin antagonists, phosphodiestase-5 inhibitors, and now a soluble guanylate cyclase activator have increased therapeutic options and potentially reduced morbidity and mortality, yet none of the current therapies have been curative. Current clinical management of PAH has become more complex given the focus on early diagnosis, an increased number of available therapeutics within each mechanistic class, as well as the emergence of clinically challenging scenarios such as perioperative care. Efforts to standardize the clinical care of PAH patients have led to the formation of multidisciplinary PAH tertiary care programs that strive to offer medical care based on peer-reviewed evidence-based and expert consensus guidelines. Furthermore, these tertiary PAH centers often support clinical and basic science research programs to gain novel insights into the pathogenesis of PAH with the goal to improve the clinical management of this devastating disease. In this manuscript, we discuss the clinical approach and management of PAH from the perspective of a single US-based academic institution. We provide an overview of currently available clinical guidelines, and offer some insight into how we approach current controversies in clinical management of certain patient subsets. We conclude with an overview of our program structure as well as a perspective on research and the role of a tertiary PAH center in contributing new knowledge to the field. PMID:24951763

  19. Coenzyme Q supplementation in pulmonary arterial hypertension

    PubMed Central

    Sharp, Jacqueline; Farha, Samar; Park, Margaret M.; Comhair, Suzy A.; Lundgrin, Erika L.; Tang, W.H. Wilson; Bongard, Robert D.; Merker, Marilyn P.; Erzurum, Serpil C.

    2014-01-01

    Mitochondrial dysfunction is a fundamental abnormality in the vascular endothelium and smooth muscle of patients with pulmonary arterial hypertension (PAH). Because coenzyme Q (CoQ) is essential for mitochondrial function and efficient oxygen utilization as the electron carrier in the inner mitochondrial membrane, we hypothesized that CoQ would improve mitochondrial function and benefit PAH patients. To test this, oxidized and reduced levels of CoQ, cardiac function by echocardiogram, mitochondrial functions of heme synthesis and cellular metabolism were evaluated in PAH patients (N=8) in comparison to healthy controls (N=7), at baseline and after 12 weeks oral CoQ supplementation. CoQ levels were similar among PAH and control individuals, and increased in all subjects with CoQ supplementation. PAH patients had higher CoQ levels than controls with supplementation, and a tendency to a higher reduced-to-oxidized CoQ ratio. Cardiac parameters improved with CoQ supplementation, although 6-minute walk distances and BNP levels did not significantly change. Consistent with improved mitochondrial synthetic function, hemoglobin increased and red cell distribution width (RDW) decreased in PAH patients with CoQ, while hemoglobin declined slightly and RDW did not change in healthy controls. In contrast, metabolic and redox parameters, including lactate, pyruvate and reduced or oxidized gluthathione, did not change in PAH patients with CoQ. In summary, CoQ improved hemoglobin and red cell maturation in PAH, but longer studies and/or higher doses with a randomized placebo-controlled controlled design are necessary to evaluate the clinical benefit of this simple nutritional supplement. PMID:25180165

  20. Renin and aldosterone measurements in the management of arterial hypertension.

    PubMed

    Viola, A; Monticone, S; Burrello, J; Buffolo, F; Lucchiari, M; Rabbia, F; Williams, T A; Veglio, F; Mengozzi, G; Mulatero, P

    2015-06-01

    Renin-angiotensin-aldosterone system (RAAS) is recognized as the main regulatory system of hemodynamics in man, and its derangements have a key role in the development and maintenance of arterial hypertension. Classification of the hypertensive states according to different patterns of renin and aldosterone levels ("RAAS profiling") allows the diagnosis of specific forms of secondary hypertension and may identify distinct hemodynamic subsets in essential hypertension. In this review, we summarize the application of RAAS profiling for the diagnostic assessment of hypertensive patients and discuss how the pathophysiological framework provided by RAAS profiling may guide therapeutic decision-making, especially in the context of uncontrolled hypertension not responding to multi-therapy. PMID:25993253

  1. [Arterial hypertension and alcoholism among workers in an oil refinery].

    PubMed

    Lima, C T; Carvalho, F M; Quadros, C de A; Gonçalves, H R; Silva Júnior, J A; Peres, M F; Bonfim, M S

    1999-09-01

    The role of alcohol ingestion in the incidence of arterial hypertension has not been completely established. In addition, there are few studies addressing this point in relation to populations of workers. The objective of this study was to evaluate the association between alcoholism and arterial hypertension among workers in an oil refinery in Mataripe, Bahia, Brazil, from 1986 to 1993. We designed a retrospective cohort study with a 7-year follow-up in a stratified systematic sample of 335 workers from the refinery. Arterial hypertension was diagnosed based on blood pressure measurements done during routine medical examinations. At the beginning of follow-up, three groups were defined using the CAGE test of alcohol dependency: nondrinkers (n = 121), CAGE-negative workers (n = 116), and CAGE-positive workers (n = 98). In comparison with the CAGE-negative group, the CAGE-positive group had both greater relative risk and greater attributable risk for developing arterial hypertension (RR = 2.58; AR = 24.95 per 1,000 person-years). The CAGE-positive group also had greater risks compared to nondrinkers (RR = 2.06; AR = 20.97 per 1,000 person-years). The attributable fractions for the same two comparisons of groups were 61% and 51%, respectively. Rate standardization by age or smoking habit did not substantially change the results. Alcoholism is an important risk factor for arterial hypertension. PMID:10517096

  2. In vivo hypertensive arterial wall uptake of radiolabeled liposomes

    SciTech Connect

    Hodis, H.N.; Amartey, J.K.; Crawford, D.W.; Wickham, E.; Blankenhorn, D.H. )

    1990-06-01

    Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with (111In)nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall.

  3. [Arterial hypertension among oil-drilling workers exposed to noise].

    PubMed

    Souto Souza, N S; Carvalho, F M; de Cássia Pereira Fernandes, R

    2001-01-01

    A cross-sectional study with a retrospective component was conducted to evaluate occupational noise exposure as a potential risk factor for arterial hypertension among 775 workers from an oil-drilling industry. Hypertension was defined as >/= 140/90mmHg. Occupational noise exposure was measured as: (1) exposure to sound pressure levels >/= 85dbA for 10 years or more and (2) moderate-to-severe noise-induced hearing loss (NIHL). The effects of age, education, shift work, and obesity were evaluated by stratification and logistic regression analysis. A positive association between occupational noise exposure and hypertension was found, using both the level/duration of noise exposure (RP = 1.8; 95% CI: 1.3-2.4) and NIHL (RP = 1.5; 95% CI: 1.1-2.0) as exposure indicators. Considering the study limits, long-term occupational noise exposure thus appears to be a risk factor for arterial hypertension. PMID:11784909

  4. [Arterial hypertension in gravidity - a risk factor for cardiovascular diseases].

    PubMed

    Kováčová, M; Kiňová, S

    2012-12-01

    Gravidity is a dynamic process and complications may occur at any stage and anytime during a thus far physiological gravidity. Such gravidity puts the mother, the foetus and, later, the newborn at a greater risk. The incidence of arterial hypertension is between 7 and 15% and is one of the 4 main causes of maternal and perinatal mortality. Cardiovascular stress test, such as gravidity, might help to identify women at a greater risk of cardiovascular diseases or with a subclinical vascular disease. Women with a history of preeclampsia are more likely to develop chronic arterial hypertension in the future either alone or associated with a cardiovascular disease. Arterial hypertension during gravidity should be considered as a risk factor for cardiovascular diseases during later stages of maternal life. Prevention of cardiovascular diseases should be a life-long aspiration. PMID:23427950

  5. Pulmonary arterial hypertension: a current review of pharmacological management.

    PubMed

    Sahni, Sonu; Ojrzanowski, Marcin; Majewski, Sebastian; Talwar, Arunabh

    2016-01-01

    Pulmonary hypertension (PHTN) is a rare and devastating disease characterized by progressive increases in pulmonary arterial pressure and pulmonary vascular resistance, which eventually leads to right ventricular failure and death. At present there is no cure for pulmonary arterial hypertension (PAH); however over the past decade targeted pharmaceutical options have become available for the treatment of PAH. Prior to evaluation for therapeutic options a definitive diagnosis of pulmonary arterial hypertension must be made via comprehensive physical exam and definitive diagnostic testing. Screening test of choice remains echocardiography and gold standard for definitive diagnosis is right heart catheterization. Once the establishment of a diagnosis of PAH is made therapeutic options may be a possibility based on a diagnostic algorithm and disease severity of the PAH patient. There are different classes of medications available with different mechanisms of actions which net a vasodilatory effect and improve exercise tolerance, quality of life as well and survival. PMID:26693827

  6. Endothelin receptor antagonists in the treatment of pulmonary arterial hypertension.

    PubMed

    Langleben, David

    2007-03-01

    The recognition that endothelin-1 contributes to the pathogenesis of pulmonary arterial hypertension has led to the development of clinically useful endothelin receptor antagonists that improve symptoms and functional capacity and alter the natural history of the disease in a beneficial way. The antagonists have varying degrees of selectivity for the two classes of endothelin receptor, termed ETA and ETB, and the varying degrees may translate into clinical differences. Endothelin receptor antagonists have become an integral part of therapy for pulmonary arterial hypertension, and the indications for their use are expanding. PMID:17338931

  7. Computational modeling of hypertensive growth in the human carotid artery

    PubMed Central

    Sáez, Pablo; Peña, Estefania; Martínez, Miguel Angel; Kuhl, Ellen

    2014-01-01

    Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively. PMID:25342868

  8. Prostanoid therapies in the management of pulmonary arterial hypertension

    PubMed Central

    LeVarge, Barbara L

    2015-01-01

    Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary artery pressure due to a high pulmonary vascular resistance state. A relative decrease in prostacyclin presence has been associated with PAH; this pathway has thus become a therapeutic target. Epoprostenol, the synthetic equivalent of prostacyclin, was first utilized as short-term or bridging therapy in the 1980s. Further refinement of its long-term use via continuous intravenous infusion followed. A randomized controlled trial by Barst et al in 1996 demonstrated functional, hemodynamic, and mortality benefits of epoprostenol use. This work was a groundbreaking achievement in the management of PAH and initiated a wave of research that markedly altered the dismal prognosis previously associated with PAH. Analogs of prostacyclin, including iloprost and treprostinil, exhibit increased stability and allow for an extended array of parenteral and non-parenteral (inhaled and oral) therapeutic options. This review further examines the pharmacology and clinical use of epoprostenol and its analogs in PAH. PMID:25848300

  9. [Pulmonary arterial hypertension associated to human immunodeficiency virus].

    PubMed

    Sandoval-Gutiérrez, José Luis; Santos-Martínez, Luis Efren; Rodríguez-Silverio, Juan; Baranda-Tovar, Francisco Martín; Rivera-Rosales, Rosa María; Flores-Murrieta, Francisco Javier

    2015-01-01

    From the advent of the highly effective antiretroviral treatment, the life expectancy of patients with human immunodeficiency virus has increased significantly. At present, the causes of death are non-infectious complications. Between them, the pulmonary arterial hypertension has a special importance. It is important early detection to establish the therapeutic, with the objective of preventing a fatal outcome to future. PMID:25577549

  10. Pulmonary Arterial Hypertension-A Deadly Complication of Systemic Sclerosis

    PubMed Central

    Pankey, Edward A; Epps, Matthew; Nossaman, Bobby D; Hyman, Albert L; Kadowitz, Philip J

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease with limited therapeutic options. Moreover, when PAH occurs in patients diagnosed with systemic sclerosis, worse outcomes are observed. The purpose of this review is to discuss the etiologies of PAH found in the systemic sclerosis patient, limitations of current medical therapies, and, finally, potential therapies for patients with this combination. PMID:23626904

  11. Resistant Hypertension due to Fibromuscular Dysplasia in a Young Male: A Rare Case Report

    PubMed Central

    Vakili, Hossein; Memaryan, Mehdi; Sadeghi, Roxana; Naderian, Mohammadreza

    2016-01-01

    Fibromuscular Dysplasia (FMD) is a sporadic non-atherosclerotic disease. FMD has been established in nearly every arterial bed. However, the most frequent arteries affected are the renal and carotid arteries. Disease presentation may vary broadly, depending upon the arterial bed complication and the severity of illness. Hypertension, particularly resistant type, headache and dizziness are the most common presentations. String of beads appearance in angiographic views due to post-stenotic aneurysms is the characteristic view. It is most commonly described in young aged females; but in rare male cases has also been reported. Moreover, balloon angioplasty is standard and effective therapy for FMD. We present a young 28-year-old man who was referred for evaluation of resistant hypertension for nearly 3 years without comprehensive workup. The patient underwent renal artery angiography which confirmed beading narrowing of the right renal artery with significant stenosis at mid portion compatible with FMD; and balloon angioplasty was done. This case highlights that FMD should be kept in mind as a rare cause of resistant hypertension in young males; although it is most common in young females.

  12. Resistant Hypertension due to Fibromuscular Dysplasia in a Young Male: A Rare Case Report.

    PubMed

    Vakili, Hossein; Khaheshi, Isa; Memaryan, Mehdi; Sadeghi, Roxana; Naderian, Mohammadreza

    2016-06-01

    Fibromuscular Dysplasia (FMD) is a sporadic non-atherosclerotic disease. FMD has been established in nearly every arterial bed. However, the most frequent arteries affected are the renal and carotid arteries. Disease presentation may vary broadly, depending upon the arterial bed complication and the severity of illness. Hypertension, particularly resistant type, headache and dizziness are the most common presentations. String of beads appearance in angiographic views due to post-stenotic aneurysms is the characteristic view. It is most commonly described in young aged females; but in rare male cases has also been reported. Moreover, balloon angioplasty is standard and effective therapy for FMD. We present a young 28-year-old man who was referred for evaluation of resistant hypertension for nearly 3 years without comprehensive workup. The patient underwent renal artery angiography which confirmed beading narrowing of the right renal artery with significant stenosis at mid portion compatible with FMD; and balloon angioplasty was done. This case highlights that FMD should be kept in mind as a rare cause of resistant hypertension in young males; although it is most common in young females. PMID:27504335

  13. Recent Strategies in Treatment of Pulmonary Arterial Hypertension, A Review

    PubMed Central

    Fallah, Flora

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. The pulmonary circulation has to accommodate the entire cardiac output in each cardiac cycle and evolution has adapted to this by making it a low-pressure high-flow system. However, pathology can affect both the arterial and venous components of this system. Pulmonary venous hypertension mainly refers to diseases that result in elevated venous pressure and occurs mainly from mitral valve and left-sided heart disease. Standard treatment options include oral anticoagulation, diuretics, oxygen supplementation, and for a small percentage of patients, calcium channel blockers. Newer treatments include prostacyclin analogues, endothelin receptor antago¬nists, and phosphodiesterase type 5 inhibitors. This article reviews the current treatments strategies for PAH and provides guidelines for its management. PMID:25946920

  14. Prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension.

    PubMed

    Lee, Noel S; Blanchard, Daniel G; Knowlton, Kirk U; McDivit, Anna M; Pretorius, Victor; Madani, Michael M; Fedullo, Peter F; Kerr, Kim M; Kim, Nick H; Poch, David S; Auger, William R; Daniels, Lori B

    2015-06-01

    This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery-pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery-pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery-pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery-pulmonary artery collateral among control subjects (0.4%; P < 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P < 0.001) or lobar arteries (P < 0.001). In conclusion, the prevalence of coronary artery-pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion. PMID:26064456

  15. Why there is a need to discuss pulmonary hypertension other than pulmonary arterial hypertension?

    PubMed

    Papathanasiou, Athanasios; Nakos, George

    2015-11-01

    Pulmonary hypertension (PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mmHg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension (PAH) is an uncommon condition with severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases (LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group I PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference (DPD, defined as diastolic pulmonary artery pressure - mean PAWP): Isolated post-capillary PH, defined as PAWP > 15 mmHg and DPD < 7 mmHg, and combined post-capillary PH and pre-capillary PH, defined as PAWP > 15 mmHg and DPD ≥ 7 mmHg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of

  16. Why there is a need to discuss pulmonary hypertension other than pulmonary arterial hypertension?

    PubMed Central

    Papathanasiou, Athanasios; Nakos, George

    2015-01-01

    Pulmonary hypertension (PH) is a condition characterized by the elevation of the mean pulmonary artery pressure above 25 mmHg and the pulmonary vascular resistance above 3 wood units. Pulmonary arterial hypertension (PAH) is an uncommon condition with severe morbidity and mortality, needing early recognition and appropriate and specific treatment. PH is frequently associated with hypoxemia, mainly chronic obstructive pulmonary disease and DPLD and/or left heart diseases (LHD), mainly heart failure with reduced or preserved ejection fraction. Although in the majority of patients with PH the cause is not PAH, a significant number of published studies are still in regard to group I PH, leading to a logical assumption that PH due to other causes is not such an important issue. So, is there a reason to discuss PH other than PAH? Chronic lung diseases, mainly chronic obstructive lung disease and DPLD, are associated with a high incidence of PH which is linked to exercise limitations and a worse prognosis. Although pathophysiological studies suggest that specific PAH therapy may benefit such patients, the results presented from small studies in regard to the safety and effectiveness of the specific PAH therapy are discouraging. PH is a common complication of left heart disease and is related to disease severity, especially in patients with reduced ejection fraction. There are two types of PH related to LHD based on diastolic pressure difference (DPD, defined as diastolic pulmonary artery pressure - mean PAWP): Isolated post-capillary PH, defined as PAWP > 15 mmHg and DPD < 7 mmHg, and combined post-capillary PH and pre-capillary PH, defined as PAWP > 15 mmHg and DPD ≥ 7 mmHg. The potential use of PAH therapies in patients with PH related to left heart disease is based on a logical pathobiological rationale. In patients with heart failure, endothelial dysfunction has been proposed as a cause of PH and hence as a target for treatment, supported by the presence of

  17. Integrated care and optimal management of pulmonary arterial hypertension

    PubMed Central

    Strange, Geoff; Fowler, Robin; Jary, Corina; Dalton, Brad; Stewart, Simon; Gabbay, Eli

    2009-01-01

    Pulmonary arterial hypertension (PAH) may occur as an idiopathic process or as a component of a variety of diseases, including connective tissue diseases, congenital heart disease, and exposure to appetite suppressants or infectious agents such as HIV. Untreated, it is a potentially devastating disease; however, diagnosis can be difficult due to the non-specific nature of symptoms during the early stages, and the fact that patients often present to a range of different medical specialties. The past decade has seen remarkable improvements in our understanding of the pathology associated with the condition and the development of PAH-specific therapies with the ability to alter the natural history of the disease. This article reviews the evidence for screening and diagnosis of susceptible patient groups and discusses treatment selection and recommendations based on data available from randomized controlled trials. In addition, due to the complexity of the diagnostic evaluation required and the treatment options available, this review mandates for a multidisciplinary approach to the management of PAH. We discuss the roles and organizational structure of a specialized PAH center in Perth, Western Australia to highlight these issues. PMID:21197349

  18. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    SciTech Connect

    Suzuki, Chihiro; Takahashi, Masafumi . E-mail: masafumi@sch.md.shinshu-u.ac.jp; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-10-20

    Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH.

  19. An update on the role of adipokines in arterial stiffness and hypertension.

    PubMed

    Sabbatini, Andréa R; Fontana, Vanessa; Laurent, Stephane; Moreno, Heitor

    2015-03-01

    Adipokines are hormones produced by adipocytes and have been involved in multiple pathologic pathways, including inflammatory and cardiovascular complications in essential hypertension. Arterial stiffness is a frequent vascular complication that represents increased cardiovascular risk in hypertensive patients. Adipokines, such as adiponectin, leptin and resistin, might be implicated in hypertension, as well as in vascular alterations associated with this condition. Arterial stiffness has proven to be a predictor of cardiovascular events. Obesity and target-organ damage such as arterial stiffness are features associated with hypertension. This review aims to update the association between adipokines and arterial stiffness in essential and resistant hypertension (RHTN). PMID:25502905

  20. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Schistosomiasis and pulmonary arterial hypertension.

    PubMed

    Butrous, Ghazwan

    2014-07-01

    Schistosomiasis is caused by infection with the parasite Schistosoma, which is a flat-worm or fluke. The dominant species are Schistosoma mansoni, Schistosoma japonicum, and Schistosoma haematobium. Schistosomiasis is the third most common parasitic disease in the world after malaria and amoebiasis. It is endemic in more than 70 countries affecting about 200 million people worldwide, of whom 80% are in sub-Saharan Africa. There are pockets of infection in north-eastern Brazil, near the Yangtze River in China, and some pockets in south East Asia. In the East Mediterranean regions, the Schistosoma have been reported in Iraq and Egypt as well as in Sudan. The latter has the highest infection rate nowadays, particularly in the Al Jazeera area, due to the poor Schistosoma control program. In the Arabian peninsula, schistosomiasis has been reported in southwest part of Saudi Arabia, mainly in the Asir province and Jizan province, which lay in the southwest corner of Saudi Arabia and directly north of the border with Yemen. The efforts to control schistosomiasis have been very successful in Saudi Arabia due to the irrigation system control. However, the infection is prone in Yemen, where the schistosomiasis control is much less strict. Thus as a result, the problem still exists due to transmigration of the populations from both countries. As a cause of pulmonary arterial hypertension (PAH), schistosomiasis is still under diagnosed and undertreated. This article with give a highlight about the pathophysiology of the disease and both diagnostic and therapeutic strategies. PMID:25076995

  1. Phosphodiesterase type 5 inhibitors in pulmonary arterial hypertension.

    PubMed

    Montani, David; Chaumais, Marie-Camille; Savale, Laurent; Natali, Delphine; Price, Laura C; Jaïs, Xavier; Humbert, Marc; Simonneau, Gérald; Sitbon, Olivier

    2009-09-01

    Pulmonary arterial hypertension (PAH) is a rare disease characterized by vascular proliferation and remodeling, resulting in a progressive increase in pulmonary arterial resistance, right heart failure, and death. The pathogenesis of PAH is multifactorial, with endothelial cell dysfunction playing an integral role. This endothelial dysfunction is characterized by an overproduction of vasoconstrictors and proliferative factors, such as endothelin-1, and a reduction of vasodilators and antiproliferative factors, such prostacyclin and nitric oxide. Phosphodiesterase type 5 (PDE-5) is implicated in this process by inactivating cyclic guanosine monophosphate, the nitric oxide pathway second messenger. PDE-5 is abundantly expressed in lung tissue, and appears to be upregulated in PAH. Three oral PDE-5 inhibitors are available (sildenafil, tadalafil, and vardenafil) and are the recommended first-line treatment for erectile dysfunction. Experimental studies have shown the beneficial effects of PDE-5 inhibitors on pulmonary vascular remodeling and vasodilatation, justifying their investigation in PAH. Randomized clinical trials in monotherapy or combination therapy have been conducted in PAH with sildenafil and tadalafil, which are therefore currently the approved PDE-5 inhibitors in PAH treatment. Sildenafil and tadalafil significantly improve clinical status, exercise capacity, and hemodynamics of PAH patients. Combination therapy of PDE-5 inhibitors with prostacyclin analogs and endothelin receptor antagonists may be helpful in the management of PAH although further studies are needed in this area. The third PDE-5 inhibitor, vardenafil, is currently being investigated in PAH. Side effects are usually mild and transient and include headache, flushing, nasal congestion, digestive disorders, and myalgia. Mild and moderate renal or hepatic failure does not significantly affect the metabolism of PDE-5 inhibitors, whereas coadministration of bosentan decreases sildenafil and

  2. Vascular reactivity of rabbit isolated renal and femoral resistance arteries in renal wrap hypertension.

    PubMed

    Khammy, Makhala M; Angus, James A; Wright, Christine E

    2016-02-15

    In rabbits with cellophane renal wrap hypertension, hindquarter and total vascular resistance changes to pressor and depressor agents are amplified compared to those of normotensive rabbits. The aim of the present study was to evaluate the in vitro pharmacodynamics of hypertensive and normotensive rabbit small artery segments isolated from the renal and hindquarter vascular beds. Using wire myography, the full range (Emax) and sensitivity (EC50) to a range of agonists of segments of renal interlobar (≈ 600 µm i.d.), renal arcuate (≈ 250 µm i.d.) and deep femoral branch (≈ 250 µm i.d.) arteries were assessed under normalised conditions of passive tension. Interlobar arteries from hypertensive rabbits were more sensitive (EC50) than those from normotensive rabbits to noradrenaline (6-fold), methoxamine (3-fold) and angiotensin II (3-fold). Arcuate artery reactivity was largely unaffected by hypertension. Deep femoral arteries from hypertensive rabbits had enhanced sensitivity only to noradrenaline (2-fold) and methoxamine (4-fold). Sensitivity to relaxation by acetylcholine was unaffected by hypertension in all arteries. Deep femoral arteries from hypertensive rabbits were more sensitive to sodium nitroprusside than normotensive counterparts. Adenosine caused little relaxation in renal arteries, but full relaxation in deep femoral arteries, unaltered by hypertension. This study found substantial heterogeneity in the pharmacodynamic profile of vessels isolated from different vascular beds and between arterial segments within the kidney. These profiles were differentially affected by hypertension suggesting that hypertension per se is not a resultant of general vascular dysfunction. PMID:26806799

  3. Inflammatory mechanisms in HIV-associated pulmonary arterial hypertension.

    PubMed

    Tcherakian, Colas; Couderc, Louis-Jean; Humbert, Marc; Godot, Véronique; Sitbon, Olivier; Devillier, Philippe

    2013-10-01

    Pulmonary arterial hypertension (PAH) is a severe complication of human immunodeficiency virus (HIV) infection and a leading major cause of death when present. HIV-PAH could be the consequence of multiple hits including the direct effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed, HIV infection has long been identified as an immunosuppressive disease but, since the advent of highly active antiretroviral treatments (HAART), HIV infection is considered as an inflammatory disease in which vascular complications have become a major cause of morbidity and death. Conversely to immunosuppression, which correlates with blood CD4 + T cell level, inflammation in HIV infection is due to the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6 overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only partially restored with HAART, usually slowly after several months or years, with a large heterogeneity from one patient to another. These characteristics may cause chronic inflammation, and we hypothesize that PAH may occur because of this inflammatory component despite HAART, even with apparently good response to therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load). Inflammation theory in HIV-PAH (as in other forms of PAH) could open new treatment options. PMID:24037631

  4. Right Ventricular Adaptation and Failure in Pulmonary Arterial Hypertension

    PubMed Central

    Ryan, John J.; Huston, Jessica; Kutty, Shelby; Hatton, Nathan D.; Bowman, Lindsay; Tian, Lian; Herr, Julia E.; Johri, Amer M.; Archer, Stephen L.

    2015-01-01

    Pulmonary arterial hypertension (PAH) is an obstructive pulmonary vasculopathy, characterized by excess proliferation, apoptosis-resistance, inflammation, fibrosis and vasoconstriction. While PAH therapies target some of these vascular abnormalities (primarily vasoconstriction) most do not directly benefit the right ventricle (RV). This is suboptimal since a patient’s functional state and prognosis are largely determined by the success of the adaptation of the RV to the increased afterload. The RV initially hypertrophies but may ultimately decompensate, becoming dilated, hypokinetic and fibrotic. A number of pathophysiologic abnormalities have been identified in the PAH RV, including: ischemia and hibernation (partially reflecting RV capillary rarefaction), autonomic activation (due to GRK2-mediated down-regulation and desensitization of β-adrenergic receptors), mitochondrial-metabolic abnormalities (notably increased uncoupled glycolysis and glutaminolysis), and fibrosis. Many RV abnormalities are detectable by molecular imaging and may serve as biomarkers. Some molecular pathways, such as those regulating angiogenesis, metabolism and mitochondrial dynamics, are similarly deranged in the RV and pulmonary vasculature, offering the possibility of therapies that treat both the RV and pulmonary circulation. An important paradigm in PAH is that the RV and pulmonary circulation constitute a unified cardiopulmonary unit. Clinical trials of PAH pharmacotherapies should assess both components of the cardiopulmonary unit. PMID:25840092

  5. [Consensus on Systemic Arterial Hypertension In México].

    PubMed

    Rosas-Peralta, Martín; Palomo-Piñón, Silvia; Borrayo-Sánchez, Gabriela; Madrid-Miller, Alejandra; Almeida-Gutiérrez, Eduardo; Galván-Oseguera, Héctor; Magaña-Serrano, José Antonio; Saturno-Chiu, Guillermo; Ramírez-Arias, Erick; Santos-Martínez, Efrén; Díaz-Díaz, Enrique; Salgado-Pastor, Selene Janette; Morales-Mora, Gerardo; Medina-Concebida, Luz Elena; Mejía-Rodríguez, Oliva; Pérez-Ruiz, Claudia Elsa; Chapa-Mejía, Luis Raúl; Álvarez-Aguilar, Cleto; Pérez-Rodríguez, Gilberto; Castro-Martínez, María Guadalupe; López-Bárcena, Joaquín; Paniagua-Sierra, José Ramón

    2016-01-01

    This Consenso Nacional de Hipertensión Arterial Sistémica (National Consensus on Systemic Arterial Hypertension) brings together experiences and joint work of 79 specialists who have been in contact with the patient affected by systemic arterial hypertension. All concepts here presented were outlined on the basis of the real world practice of Mexican hypertensive population. The consensus was developed under strict methodological guidelines. The Delphi technique was applied in two rounds for the development of an appropriate statistical analysis of the concepts exposed by all the specialists, who posed key questions, later developed by the panel of experts of the Hospital de Cardiología, and specialists from the Centro Médico Nacional. Several angles of this illness are shown: detection, diagnosis, pathophysiology, classification, treatment and prevention. The evidence analysis was carried out using PRISMA method. More than 600 articles were reviewed, leaving only the most representative in the references. This document concludes with practical and useful recommendations for the three levels of health care of our country. PMID:27284844

  6. Regional differences in the prevalence of arterial hypertension in Croatia.

    PubMed

    Erceg, Marijan; Kern, Josipa; Babić-Erceg, Andrea; Ivicević-Uhernik, Ana; Vuletić, Silvije

    2009-04-01

    This paper analyzes the Croatian Adult Health Survey data, collected in 2003 with a total of 9,070 respondents aged 18+. Based on an average of two measurements, respondents with the mean systolic arterial pressure > or = 140 mmHg or mean diastolic pressure > or = 90 mmHg were classified as hypertensive. The data for men and women were analyzed separately, according to regions. Prevalence of hypertension in men was 40.5% (95% confidence interval CI 37.9-43.01; coefficient of variability CV = 3.2), women 34.9% (95% CI 33.2-36.7; CV 2.5). There were no significant differences in regional prevalence in men, except in the Northern and Eastern region. In women we did not detect any significant regional difference. Non-controlled arterial hypertension is an important public health problem in all monitored regions of Croatia. Raising awareness about the problem, early detection and encouraging the population to adhere to the therapy for elevated arterial pressure, in addition to a healthy life style, are important for successful control and harm reduction. PMID:19563141

  7. Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

    PubMed Central

    Arnold, Nadine D.; Chang, William; Watson, Oliver; Swift, Andrew J.; Condliffe, Robin; Elliot, Charlie A.; Kiely, David G.; Suvarna, S. Kim; Gunn, Julian; Lawrie, Allan

    2015-01-01

    Background— Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results— Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions— Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety. PMID:26553697

  8. Job absenteeism and arterial hypertension: results of a hypertension control program.

    PubMed

    Ruiz de la Fuente Tirado, S; Cortina Greus, P; Alfonso Sanchez, J L; Saiz Sanchez, C; Sabater Pons, A; Gonzalez Arraez, J I; Cortes Vizcaino, C

    1992-09-01

    This study reports the findings of one of the stages of a programme for the detection and control of arterial hypertension, started in 1980 in an automobile company with a workforce of 9,782. In the initial screening, 522 hypertensive males were found using epidemiological criteria and 206 of these fulfilled the criteria of definite hypertension. The objective of this study consisted of evaluating, 9 years after the start of the program, the indirect cost in terms of the reduction in the morbidity indicator-temporary work incapacity (TWI). Analysis is based on a comparison of the prevalence of hypertension in the population when the program was begun (6%) and in 1989 (9.8%). It can be observed that the TWI rate of the hypertensive population was significantly higher than that of the rest of the workforce, and that this remained true for the reference group (RG) hypertensives a year after the study was initiated. In contrast, the intervention group (IG) showed significantly lower TWI levels, not only in comparison with the RG but also with the rest of the workers. The estimated reduction in TWI for 1989 was 4.500 days/year, which corresponds to an estimated saving of 76.500.000 pesetas/year. PMID:1426165

  9. Transcatheter Treatment of “Pulmonary Artery Hypertension” due to Patent Ductus Arteriosus and Pulmonary Artery Stenosis

    PubMed Central

    Gaio, Gianpiero; Santoro, Giuseppe; D'Alto, Michele; Palladino, Maria Teresa; Russo, Maria Giovanna; Caianiello, Giuseppe; Calabrò, Raffaele

    2006-01-01

    The association between large, left-sided patent ductus arteriosus and severe, peripheral, right pulmonary artery stenosis with no other cardiac malformation is an unreported condition that might be misdiagnosed as pulmonary hypertension due to long-standing ductal shunt. A 57-year-old man with supposed hypertensive patent ductus arteriosus underwent confirmatory cardiac catheterization. At angiography, a severe pre-hilar right pulmonary artery stenosis (peak pressure gradient, 65 mmHg) was found to complicate the hemodynamic picture of a moderate-to-large patent ductus arteriosus (QP/QS, 1.7:1), by causing pulmonary hypertension (mean pressure, 65 mmHg) and left-to-right pulmonary flow imbalance. Both lesions were treated in a single procedure of right pulmonary artery stenting and patent ductus arteriosus closure, after which the pulmonary artery pressure significantly decreased (mean, 35 mmHg). In our opinion, a thorough hemodynamic evaluation followed by pulmonary angiography should be mandatory before proceeding to patent ductus arteriosus closure in the adult patient who has “hypertensive” ductus, in whom possible associated malformations can be missed due to a poor echocardiographic window. PMID:17041703

  10. Continuous inhaled iloprost in a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension.

    PubMed

    Dykes, John C; Torres, Marilyn; Alexander, Plato J

    2016-03-01

    This report describes the case of a neonate with d-transposition of the great arteries and severe pulmonary arterial hypertension stabilised in the post-operative period with continuous iloprost nebulisation. To our knowledge, this is the first documented method of treating post-operative severe pulmonary arterial hypertension with continuous inhaled iloprost in a patient with complex CHD. We found this method of delivering the drug very effective in stabilising haemodynamic swings in the setting of severe pulmonary arterial hypertension. PMID:26220108

  11. Effect of angiotensin-induced hypertension on rat coronary arteries and myocardium.

    PubMed Central

    Giacomelli, F.; Anversa, P.; Wiener, J.

    1976-01-01

    Acute hypertension has been produced in rats by the intravenous infusion of angiotensin amide for 4 hours. Both control and hypertensive animals were injected intravenously prior to sacrifice with either horseradish peroxidase (HRP) or colloidal carbon. Epicardial arteries and blocks of ventricular myocardium containing intramyocardial arteries and arterioles have been processed for electron microscopy. HRP appears to penetrate the endoethelium of epicardial arteries from control animals within vesicles that bypass endothelial junctions and empty into interendoethelial clefts. Peroxidase does not traverse the endothelium of intramural arteries and arterioles of controls over the 10-minute period of observation. There is acceleration of lateral vesicular transport in the endothelium of epicardial arteries after angiotensin infusion and direct permeation of interendothelial clefts of intramural arterial vessels. Medial fragmentation and more extensive necrosis are observed in intramyocardial but not in epicardial arterial vessels. Foci of myocardial damage resembling irreversible ischemic or anoxic injury followed by reflow are described. It is suggested that the increased permeability of epicardial arteries may be due to elevated pressure, while the altered permeability and vascular lesions of intramural arteries and arterioles are more readily attributable to the vasoconstriction produced by angiotension. The vascular and myocardial lesions are also discussed in relation to the regional actions of angiotensin on the coronary circulation and known effects of this vasoactive peptide on myocardium. Images Figure 19 Figure 26 Figure 27 Figure 28 Figure 1 Figure 2 Figures 20 and 21 Figure 29 Figure 30 Figure 3 Figure 4 Figures 5-8 Figure 9 Figure 22 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 23 Figure 24 Figure 25 Figure 16 Figure 17 Figure 18 PMID:937512

  12. Arterial baroreceptors in the management of systemic hypertension

    PubMed Central

    Kougias, Panagiotis; Weakley, Sarah M.; Yao, Qizhi; Lin, Peter H.; Chen, Changyi

    2010-01-01

    Summary Hypertension is a multifactorial disease associated with significant morbidity. Increased sympathetic nervous system activity has been noted as an important etiologic factor and is, in part, regulated by afferent input arising from arterial and cardiopulmonary baroreceptors, activation of which causes inhibition of sympathetic output. It was thought for many years that baroreceptors control only short-term blood pressure changes, a conclusion stemming from observations in sinoaortic denervation (SAD) animal models and the phenomenon of rapid baroreceptor resetting, also seen in animal models. Newer observations, however, indicate that SAD is rather imperfect and resetting is rarely complete. Recent studies reveal that baroreceptors control sympathetic output on a more long-term basis and participate in fluid volume regulation by the kidney, and thus have the potential to adjust blood pressure chronically. Importantly, these findings are consistent with studies and observations in humans. Meanwhile, a model of electrical stimulation of the carotid sinus has been developed and successfully tested in animals. Following these encouraging results human trials to evaluate the clinical application of electrical carotid sinus manipulation in the treatment of systemic hypertension have commenced, and results so far indicate that this represents an exciting potential tool in the clinician’s armament against chronic arterial hypertension. PMID:20037502

  13. Pre-treatment considerations in childhood hypertension due to chronic kidney disease.

    PubMed

    Olowu, Wasiu Adekunle

    2015-11-01

    Hypertension (HTN) develops very early in childhood chronic kidney disease (CKD). It is linked with rapid progression of kidney disease, increased morbidity and mortality hence the imperative to start anti-hypertensive medication when blood pressure (BP) is persistently > 90(th) percentile for age, gender, and height in non-dialyzing hypertensive children with CKD. HTN pathomechanism in CKD is multifactorial and complexly interwoven. The patient with CKD-associated HTN needs to be carefully evaluated for co-morbidities that frequently alter the course of the disease as successful treatment of HTN in CKD goes beyond life style modification and anti-hypertensive therapy alone. Chronic anaemia, volume overload, endothelial dysfunction, arterial media calcification, and metabolic derangements like secondary hyperparathyroidism, hyperphosphataemia, and calcitriol deficiency are a few co-morbidities that may cause or worsen HTN in CKD. It is important to know if the HTN is caused or made worse by the toxic effects of medications like erythropoietin, cyclosporine, tacrolimus, corticosteroids and non-steroidal anti-inflammatory drugs. Poor treatment response may be due to any of these co-morbidities and medications. A satisfactory hypertensive CKD outcome, therefore, depends very much on identifying and managing these co-morbid conditions and HTN promoting medications promptly and appropriately. This review attempts to point attention to factors that may affect successful treatment of the hypertensive CKD child and how to attain the desired therapeutic BP target. PMID:26558187

  14. Successful treatment of aortic root abscess in a patient with pulmonary arterial hypertension

    PubMed Central

    Duarte, Alexander G.

    2015-01-01

    Abstract Continuous prostanoid infusion is an established treatment for pulmonary arterial hypertension that has led to improvements in symptoms, exercise tolerance, and survival. Patients with pulmonary arterial hypertension (PAH) who develop sepsis frequently experience clinical and hemodynamic deterioration associated with poor outcomes. Successful management of sepsis involves identification of the source of infection, early antimicrobial administration, judicious fluid resuscitation, and continuation of specific PAH therapies. We describe successful management of a patient with idiopathic PAH receiving chronic intravenous prostacyclin therapy who developed an aortic root abscess due to Clostridium perfringens requiring emergent aortic root repair. Management involved imaging studies, removal of potential sources with administration of intravenous antibiotics, and cautious fluid administration with hemodynamic monitoring. A multidisciplinary group led by a PAH specialist worked cohesively before, during, and after surgical intervention and achieved a successful outcome. PMID:26697181

  15. Altered artery mechanics and structure in monocrotaline pulmonary hypertension.

    PubMed

    Langleben, D; Szarek, J L; Coflesky, J T; Jones, R C; Reid, L M; Evans, J N

    1988-11-01

    Pulmonary hypertension in rats, induced by an injection of monocrotaline, is associated with changes in the wall structure of the pulmonary arterial bed. We have studied the effects of this remodeling on mechanical properties of cylindrical pulmonary artery segments from rats 21 days after monocrotaline (MCT) injection. Resting and active (KCl induced) circumference-tension relationships were established for segments of extrapulmonary and intrapulmonary arteries isolated from the hilum and the fifth lateral branch from the axial pathway (all preacinar). The thicknesses of the vessel wall, the media, and adventitia were measured at several positions around the circumference of the artery by computerized analysis of histological cross sections of the segments fixed at a standard circumference. Resting and active stress were also calculated. The study shows that active circumferential tension and active stress are reduced in vessels from MCT-treated rats. Based on our findings, it is unlikely that altered contractile function of preacinar arteries contributes significantly to the increased vascular resistance seen in this model. PMID:3145283

  16. Responses of mean arterial pressure to pressor agents and diuretics in renal hypertensive and salt hypertensive rats

    PubMed Central

    Nicholas, T. E.

    1971-01-01

    1. The responses of the mean arterial pressure to (—)-noradrenaline, tyramine, angiotensin II-val5-amide, vasopressin and rat renin have been contrasted in renal hypertensive and in salt plus desoxycorticosterone hypertensive rats. The responses were measured in rats both unanaesthetized and rats anaesthetized with pentobarbitone. 2. Responses of unanaesthetized, ganglion blocked renal hypertensive rats to noradrenaline, tyramine and vasopressin markedly exceeded, and to angiotensin II and renin were markedly smaller than, those of unanaesthetized ganglion blocked salt + DOC hypertensive animals. Responses to angiotensin and to renin were apparently enhanced in the latter animals. 3. Hydrochlorothiazide and frusemide markedly reduced mean arterial pressure in salt + DOC hypertensive rats before and after ganglionic blockade. 4. Neither diuretic caused significant reduction in the mean arterial pressures of unanaesthetized, renal hypertensive rats in the absence of ganglionic blockade: frusemide did so in anaesthetized and unanaesthetized rats after ganglionic blockade. 5. Whereas the diuretics did not affect the responses of the renal hypertensive rats to pressor agents, frusemide and to a lesser extent hydrochlorothiazide tended to depress the responses to pressor agents in salt induced hypertension. 6. Hydrochlorothiazide did not influence mean arterial pressure in unanaesthetized rats with neurogenic hypertension. PMID:4326321

  17. Pulmonary Arterial Hypertension: A Focus on Infused Prostacyclins.

    PubMed

    Stewart, Traci

    2016-01-01

    Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and cell proliferation in the pulmonary vasculature. Guideline-driven interventions with infused prostacyclin treatment are the mainstay for patients with advanced symptoms. Infused prostacyclin therapy is complex. It is critical to manage prostacyclin therapy with precision because boluses or interruptions can be fatal. Education of patients and inpatient staff nurses is necessary to prevent negative outcomes. Nurses are an essential part of the multidisciplinary team caring for patients with PAH. The diagnostic evaluation and treatment of PAH are reviewed here, and challenges associated with the care of patients on prostacyclin therapy are discussed. PMID:27598071

  18. Connective tissue disease-associated pulmonary arterial hypertension.

    PubMed

    Sung, Yon K; Chung, Lorinda

    2015-05-01

    Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling of pulmonary arterioles that leads to increased pulmonary vascular resistance, right heart failure, and death. It is associated with connective tissue diseases, including systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease. PAH is characterized by dyspnea on exertion and fatigue. Syncopal events suggest severe disease. Patients may present with signs of right heart failure. One- and 3-year survival rates are approximately 81% and 52%, respectively. Given the high prevalence and mortality, algorithms for screening are currently under investigation and will hopefully lead to earlier diagnosis and improved survival. PMID:25836644

  19. Cardiac Autonomic Drive during Arterial Hypertension and Metabolic Disturbances.

    PubMed

    Kseneva, S I; Borodulina, E V; Trifonova, O Yu; Udut, V V

    2016-06-01

    ANS support of the cardiac work was assessed with analysis of heart rate variability in representative samples of patients with arterial hypertension and metabolic disturbances manifested by overweight, classes I-II obesity, compromised glucose tolerance, and type II diabetes. Initially enhanced sympathetic effects on the heart rate demonstrated no further increase during the orthostatic test in contrast to suprasegmentary influences enhanced by this test. The pronouncedness of revealed peculiarities in ANS drive to the heart correlated with metabolic disturbances, and these peculiarities attained maximum in patients with type II diabetes. PMID:27383176

  20. Oscillatory contractions in tail arteries from genetically hypertensive rats.

    PubMed

    Lamb, F S; Myers, J H; Hamlin, M N; Webb, R C

    1985-01-01

    This study characterizes a cellular mechanism for oscillatory contractions induced by norepinephrine in vascular smooth muscle from spontaneously hypertensive stroke prone rats (SHRSP). Helically cut strips of tail arteries from SHRSP and normotensive Wistar-Kyoto rats (WKY) were mounted in a muscle bath for measurement of isometric force generation. Norepinephrine-induced responses of arteries from SHRSP were characterized by fluctuations in contractile activity, whereas those in arteries from WKY remained constant with time. The magnitude of the oscillatory contractile activity (frequency X mean amplitude) varied directly with norepinephrine concentration (5.9 X 10(-9) to 1.8 X 10(-7) M). The oscillatory contractile activity varied inversely with the potassium concentration (3-20 mM) of the buffer solution and directly with the calcium concentration (0.1-5.0 mM) of the buffer solution. The oscillatory activity was converted to maintained contraction by barium (10(-4) M), quinidine (3 X 10(-6) M), sparteine (10(-3) M), D-600 (10(-7) M), and nifedipine (10(-8) M). Tetraethylammonium and 3,4-diaminopyridine, inhibitors of voltage-dependent potassium channels, did not alter the oscillatory contractile activity induced by norepinephrine. These observations suggest that oscillatory contractile activity in tail arteries from SHRSP is caused by an abnormal variation in potassium efflux during stimulation with norepinephrine. The altered potassium efflux appears to be related to calcium entry, which is sensitive to inhibition by channel blockers. This altered membrane property may contribute to changes in vascular sensitivity in hypertension. PMID:3997233

  1. Molecular Mechanisms of Pulmonary Vascular Remodeling in Pulmonary Arterial Hypertension

    PubMed Central

    Leopold, Jane A.; Maron, Bradley A.

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease that is precipitated by hypertrophic pulmonary vascular remodeling of distal arterioles to increase pulmonary artery pressure and pulmonary vascular resistance in the absence of left heart, lung parenchymal, or thromboembolic disease. Despite available medical therapy, pulmonary artery remodeling and its attendant hemodynamic consequences result in right ventricular dysfunction, failure, and early death. To limit morbidity and mortality, attention has focused on identifying the cellular and molecular mechanisms underlying aberrant pulmonary artery remodeling to identify pathways for intervention. While there is a well-recognized heritable genetic component to PAH, there is also evidence of other genetic perturbations, including pulmonary vascular cell DNA damage, activation of the DNA damage response, and variations in microRNA expression. These findings likely contribute, in part, to dysregulation of proliferation and apoptosis signaling pathways akin to what is observed in cancer; changes in cellular metabolism, metabolic flux, and mitochondrial function; and endothelial-to-mesenchymal transition as key signaling pathways that promote pulmonary vascular remodeling. This review will highlight recent advances in the field with an emphasis on the aforementioned molecular mechanisms as contributors to the pulmonary vascular disease pathophenotype. PMID:27213345

  2. Circulating Angiogenic Precursors in Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Asosingh, Kewal; Aldred, Micheala A.; Vasanji, Amit; Drazba, Judith; Sharp, Jacqueline; Farver, Carol; Comhair, Suzy A.A.; Xu, Weiling; Licina, Lauren; Huang, Lan; Anand-Apte, Bela; Yoder, Mervin C.; Tuder, Rubin M.; Erzurum, Serpil C.

    2008-01-01

    Vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH) involves hyperproliferative and apoptosis-resistant pulmonary artery endothelial cells. In this study, we evaluated the relative contribution of bone marrow-derived proangiogenic precursors and tissue-resident endothelial progenitors to vascular remodeling in IPAH. Levels of circulating CD34+CD133+ bone marrow-derived proangiogenic precursors were higher in peripheral blood from IPAH patients than in healthy controls and correlated with pulmonary artery pressure, whereas levels of resident endothelial progenitors in IPAH pulmonary arteries were comparable to those of healthy controls. Colony-forming units of endothelial-like cells (CFU-ECs) derived from CD34+CD133+ bone marrow precursors of IPAH patients secreted high levels of matrix metalloproteinase-2, had greater affinity for angiogenic tubes, and spontaneously formed disorganized cell clusters that increased in size in the presence of transforming growth factor-β or bone morphogenetic protein-2. Subcutaneous injection of NOD SCID mice with IPAH CFU-ECs within Matrigel plugs, but not with control CFU-ECs, produced cell clusters in the Matrigel and proliferative lesions in surrounding murine tissues. Thus, mobilization of high levels of proliferative bone marrow-derived proangiogenic precursors is a characteristic of IPAH and may participate in the pulmonary vascular remodeling process. PMID:18258847

  3. Ambrisentan for the treatment of pulmonary arterial hypertension: improving outcomes

    PubMed Central

    Elshaboury, Soha M; Anderson, Joe R

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature that is associated with severe functional impairment and a poor prognosis. Ambrisentan is a selective endothelin type A receptor antagonist approved for the treatment of patients with PAH World Health Organization group 1. The efficacy and safety of ambrisentan has been evaluated in the ARIES series (Ambrisentan for the Treatment of Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies), which has established its use as both monotherapy or in conjunction with other PAH therapies. Specifically, ambrisentan is effective at increasing exercise tolerance, decreasing the risk of functional class deterioration, and prolonging time to clinical worsening. Further, ambrisentan has a favorable effect on mortality, with an 88% patient survival rate after two years of therapy compared with a 61% survival rate as estimated by the National Institute of Health Registry. Ambrisentan is generally well tolerated in all patient groups, with the main side effects of peripheral edema, sinusitis, flushing, and nasal congestion considered to be mild to moderate in nature. Ambrisentan has several favorable qualities that potentially make it more acceptable to patients, including once-daily administration, limited adverse drug reactions and drug-drug interactions, and minimal risk of liver enzyme elevation. Because of the potential risk of teratogenicity associated with ambrisentan, it is only available through a limited distribution program, ie, LEAP (the Letairis Education and Access Program). Ongoing clinical trials will help to clarify the role of ambrisentan in the treatment of PAH. PMID:23674888

  4. Novel Approaches to Treat Experimental Pulmonary Arterial Hypertension: A Review

    PubMed Central

    Umar, S.; Steendijk, P.; Ypey, D. L.; Atsma, D. E.; van der Wall, E. E.; Schalij, M. J.; van der Laarse, A.

    2010-01-01

    Background. Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by an increase in pulmonary artery pressure leading to right ventricular (RV) hypertrophy, RV failure, and ultimately death. Current treatments can improve symptoms and reduce severity of the hemodynamic disorder but gradual deterioration in their condition often necessitates a lung transplant. Methods and Results. In experimental models of PAH, particularly the model of monocrotaline-induced pulmonary hypertension, efficacious treatment options tested so far include a spectrum of pharmacologic agents with actions such as anti-mitogenic, proendothelial function, proangiogenic, antiinflammatory and antioxidative. Emerging trends in PAH treatment are gene and cell therapy and their combination, like (progenitor) cells enriched with eNOS or VEGF gene. More animal data should be collected to investigate optimal cell type, in vitro cell transduction, route of administration, and number of cells to inject. Several recently discovered and experimentally tested interventions bear potential for therapeutic purposes in humans or have been shown already to be effective in PAH patients leading to improved life expectation and better quality of life. Conclusion. Since many patients remain symptomatic despite therapy, we should encourage research in animal models of PAH and implement promising treatments in homogeneous groups of PAH patients. PMID:20339474

  5. Pulmonary arterial hypertension: a comparison between children and adults

    PubMed Central

    Barst, R.J.; Ertel, S.I.; Beghetti, M.; Ivy, D.D.

    2011-01-01

    The characteristics of pulmonary arterial hypertension (PAH), including pathology, symptoms, diagnosis and treatment are reviewed in children and adults. The histopathology seen in adults is also observed in children, although children have more medial hypertrophy at presentation. Both populations have vascular and endothelial dysfunction. Several unique disease states are present in children, as lung growth abnormalities contribute to pulmonary hypertension. Although both children and adults present at diagnosis with elevations in pulmonary vascular resistance and pulmonary artery pressure, children have less heart failure. Dyspnoea on exertion is the most frequent symptom in children and adults with PAH, but heart failure with oedema occurs more frequently in adults. However, in idiopathic PAH, syncope is more common in children. Haemodynamic assessment remains the gold standard for diagnosis, but the definition of vasoreactivity in adults may not apply to young children. Targeted PAH therapies approved for adults are associated with clinically meaningful effects in paediatric observational studies; children now survive as long as adults with current treatment guidelines. In conclusion, there are more similarities than differences in the characteristics of PAH in children and adults, resulting in guidelines recommending similar diagnostic and therapeutic algorithms in children (based on expert opinion) and adults (evidence-based). PMID:21357924

  6. Pulmonary arterial hypertension (ascites syndrome) in broilers: a review.

    PubMed

    Wideman, R F; Rhoads, D D; Erf, G F; Anthony, N B

    2013-01-01

    Pulmonary arterial hypertension (PAH) syndrome in broilers (also known as ascites syndrome and pulmonary hypertension syndrome) can be attributed to imbalances between cardiac output and the anatomical capacity of the pulmonary vasculature to accommodate ever-increasing rates of blood flow, as well as to an inappropriately elevated tone (degree of constriction) maintained by the pulmonary arterioles. Comparisons of PAH-susceptible and PAH-resistant broilers do not consistently reveal differences in cardiac output, but PAH-susceptible broilers consistently have higher pulmonary arterial pressures and pulmonary vascular resistances compared with PAH-resistant broilers. Efforts clarify the causes of excessive pulmonary vascular resistance have focused on evaluating the roles of chemical mediators of vasoconstriction and vasodilation, as well as on pathological (structural) changes occurring within the pulmonary arterioles (e.g., vascular remodeling and pathology) during the pathogenesis of PAH. The objectives of this review are to (1) summarize the pathophysiological progression initiated by the onset of pulmonary hypertension and culminating in terminal ascites; (2) review recent information regarding the factors contributing to excessively elevated resistance to blood flow through the lungs; (3) assess the role of the immune system during the pathogenesis of PAH; and (4) present new insights into the genetic basis of PAH. The cumulative evidence attributes the elevated pulmonary vascular resistance in PAH-susceptible broilers to an anatomically inadequate pulmonary vascular capacity, to excessive vascular tone reflecting the dominance of pulmonary vasoconstrictors over vasodilators, and to vascular pathology elicited by excessive hemodynamic stress. Emerging evidence also demonstrates that the pathogenesis of PAH includes characteristics of an inflammatory/autoimmune disease involving multifactorial genetic, environmental, and immune system components. Pulmonary

  7. A Huge Thrombosed Pulmonary Artery Aneurysm without Pulmonary Hypertension in a Patient with Hepatosplenic Schistosomiasis

    PubMed Central

    Abo-Salem, Elsayed S.; Ramadan, Mahmoud M.

    2015-01-01

    Patient: Male, 55 Final Diagnosis: Thrombosed pulmonary artery aneurysm Symptoms: Cough productive • fever • shortness of breath Medication: — Clinical Procedure: Pericardiocentesis Specialty: Cardiology Objective: Rare disease Background: We herein report a case of huge pulmonary artery aneurysm in a 55-year-old male farmer from the Nile delta (Lower-Egypt), mostly due to infestation with Schistosoma mansoni, which is the parasite causing hepatosplenic schistosomiasis. Case Report: This male patient was admitted with a month-long history of progressive shortness of breath, 2-month history of fever, and a cough with mucoid sputum for 10 days. On examination, he had normal temperature and blood pressure, but he had tachypnea, tachycardia, and congested neck veins. Electrocardiography showed multifocal atrial tachycardia and right bundle branch block. Conclusions: The present case is unique in that it shows the presence of a huge pulmonary artery aneurysm despite the absence of pulmonary hypertension. PMID:25746428

  8. Arterial hypertension: which targets in over-75-year people?

    PubMed

    Mureddu, Gian Francesco

    2016-01-01

    Arterial hypertension has always been considered the main risk factor in cardiovascular prevention. However, the goals of anti-hypertensive treatment (targets) in the elderly has long been under discussion. The results of the studies in favor of the hypothesis "the lower the better" than those that argue against the existence of the phenomenon of the J-curve, that is, the hypothesis according to which mortality increases to too low pressure values lower than 115/75 mmHg, are still controversial. However, in elderly patients the association between blood pressure lowering and increased cardiovascular events seems to depend on the general health status, that means the presence of comorbidity, frailty and / or disability. Recent data from the SPRINT study show that the benefit of an intensive blood pressure target (SBP <120 mmHg) compared to a usual target (SBP <140 mmHg), appears to be greater in the oldest hypertensive patients (≥75 years). The cardio-geriatric functional assessment can provide useful information to better stratify the elderly and to define more accurately the pressure targets, the choice is individual. PMID:27374038

  9. Arterial hypertension in the female world: pathophysiology and therapy.

    PubMed

    Cadeddu, Christian; Franconi, Flavia; Cassisa, Laura; Campesi, Ilaria; Pepe, Alessia; Cugusi, Lucia; Maffei, Silvia; Gallina, Sabina; Sciomer, Susanna; Mercuro, Giuseppe

    2016-04-01

    Hypertension is a major risk factor for cardiovascular disease and outcomes in women, and antihypertensive therapy is not always successful in achieving control over the blood pressure (BP). Nonoptimal control of BP remains a crucial risk factor for cardiovascular mortality, and in women, it could be related to sex-specific factors. Historically, women have been under-represented in clinical trials; therefore, the benefits of clinical outcomes and the safety profiles of antihypertensive therapies have been studied less extensively in women. The reasons for the sex differences in BP levels are multifactorial, implying different roles of the sex hormones, the renin-angiotensin system, sympathetic activity, and arterial stiffness. A complete understanding of the pathophysiological features of these differences requires further investigation.Nevertheless, the prevalence of the use of antihypertensive agents is higher among middle-aged women than among men. Notably, in the United States, hypertensive women use more diuretics and angiotensin receptor blockers than men, whereas hypertensive men more often receive beta-blockers, calcium channel antagonists, or inhibitors of angiotensin-converting enzyme. To date, the explanations for these sex differences in the consumption of antihypertensive drugs remain unknown. PMID:26910607

  10. Protein disulfide isomerase expression increases in resistance arteries during hypertension development. Effects on Nox1 NADPH oxidase signaling

    PubMed Central

    Androwiki, Aline C. D.; Camargo, Lívia de Lucca; Sartoretto, Simone; Couto, Gisele K.; Ribeiro, Izabela M. R.; Veríssimo-Filho, Sidney; Rossoni, Luciana V.; Lopes, Lucia R.

    2015-01-01

    NADPH oxidases derived reactive oxygen species (ROS) play an important role in vascular function and remodeling in hypertension through redox signaling processes. Previous studies demonstrated that protein disulfide isomerase (PDI) regulates Nox1 expression and ROS generation in cultured vascular smooth muscle cells. However, the role of PDI in conductance and resistance arteries during hypertension development remains unknown. The aim of the present study was to investigate PDI expression and NADPH oxidase dependent ROS generation during hypertension development. Mesenteric resistance arteries (MRA) and thoracic aorta were isolated from 6, 8, and 12 week-old spontaneously hypertensive (SHR) and Wistar rats. ROS production (dihydroethidium fluorescence), PDI (WB, imunofluorescence), Nox1 and NOX4 (RT-PCR) expression were evaluated. Results show a progressive increase in ROS generation in MRA and aorta from 8 to 12 week-old SHR. This effect was associated with a concomitant increase in PDI and Nox1 expression only in MRA. Therefore, suggesting a positive correlation between PDI and Nox1 expression during the development of hypertension in MRA. In order to investigate if this effect was due to an increase in arterial blood pressure, pre hypertensive SHR were treated with losartan (20 mg/kg/day for 30 days), an AT1 receptor antagonist. Losartan decreased blood pressure and ROS generation in both vascular beds. However, only in SHR MRA losartan treatment lowered PDI and Nox1 expression to control levels. In MRA PDI inhibition (bacitracin, 0.5 mM) decreased Ang II redox signaling (p-ERK 1/2). Altogether, our results suggest that PDI plays a role in triggering oxidative stress and vascular dysfunction in resistance but not in conductance arteries, increasing Nox1 expression and activity. Therefore, PDI could be a new player in oxidative stress and functional alterations in resistance arteries during the establishment of hypertension. PMID:25870854

  11. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary arterial hypertension associated with connective tissue diseases

    PubMed Central

    Boueiz, Adel; Hassoun, Paul M.

    2014-01-01

    The explosive growth of medical literature on pulmonary hypertension (PH) has led to a steady increase in awareness of this disease within the medical community during the past decade. The recent revision of the classification of PH is presented in in the main guidelines. Group 1 PH or pulmonary arterial hypertension (PAH) is a heterogeneous group and includes PH due to inheritable, drug-induced, and toxin-induced causes and to such underlying systemic causes as connective tissue diseases, human immunodeficiency viral infection, portal hypertension, congenital heart disease, and schistosomiasis. Systemic sclerosis (SSc) is an autoimmune multisystem disorder, which affects over 240 persons per million in the United States.[1] Its manifestations are not confined to the skin but may also involve the lungs, kidneys, peripheral circulation, musculoskeletal system, gastrointestinal tract, and heart. The outcome of PAH associated with SSc is worse when compared to other subtypes of PAH. In this review, we summarize available information about the pulmonary vascular and cardiac manifestations of SSc with special emphasis on their prognostic implications as well as the peculiarity of their detection. PMID:25076994

  12. Impact of residual stretch and remodeling on collagen engagement in healthy and pulmonary hypertensive calf pulmonary arteries at physiological pressures.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Albietz, Joseph A; Stenmark, Kurt R; Qi, H Jerry; Shandas, Robin; Hunter, Kendall S

    2012-07-01

    Understanding the mechanical behavior of proximal pulmonary arteries (PAs) is crucial to evaluating pulmonary vascular function and right ventricular afterload. Early and current efforts focus on these arteries' histological changes, in vivo pressure-diameter behavior and mechanical properties under in vitro mechanical testing. However, the in vivo stretch and stress states remain poorly characterized. To further understand the mechanical behavior of the proximal PAs under physiological conditions, this study computed the residual stretch and the in vivo circumferential stretch state in the main pulmonary arteries in both control and hypertensive calves by using in vitro and in vivo artery geometry data, and modeled the impact of residual stretch and arterial remodeling on the in vivo circumferential stretch distribution and collagen engagement in the main pulmonary artery. We found that the in vivo circumferential stretch distribution in both groups was nonuniform across the vessel wall with the largest stretch at the outer wall, suggesting that collagen at the outer wall would engage first. It was also found that the circumferential stretch was more uniform in the hypertensive group, partially due to arterial remodeling that occurred during their hypoxic treatment, and that their onset of collagen engagement occurred at a higher pressure. It is concluded that the residual stretch and arterial remodeling have strong impact on the in vivo stretch state and the collagen engagement and thus the mechanical behavior of the main pulmonary artery in calves. PMID:22237861

  13. [CHANGES OF CAROTID AND VERTEBRAL ARTERIES IN PATENTS WITH ARTERIAL HYPERTENSION AND HEPATOBILIARY PATHOLOGY].

    PubMed

    Polyakov, V Ya; Nikolaev, Yu A; Pegova, S V; Matsievskaya, T R; Obukhov, I V

    2016-01-01

    The study included 1172 patients (410 men and 762 women) at the mean age of 60.3 ± 10.4 years with grade I-II (stage I-II) arterial hypertension (AH) admitted to the clinic of Institute of Experimental Medicine. The patients were divided into 2 groups based on the results of clinical and laboratory diagnostics. Group 1 (n = 525) included patients with AH and hepatobiliary system (HBS) diseases, group 2 (n = 647) patients with AH without HBS diseases. The patients group 1 had a thicker intima-media complex of carotid arteries, higher peak systolic bloodflow rate in the internal and vertebral carotid arteries, more pronounced coiling of internal carotid arteries than patients of group 2. Patients with AH and HBS diseases exhibited correlation between bloodflow rate in external carotid arteries and atherogenicity coefficient. Duplex scanning of neck vessels of in patients with AH without HBS diseases revealed peculiar changes of the intima-media thickness and hemodynamically significant changes of the blood flow in the internal carotid arteries that may be of prognostic value in this nosological syntropy and require the personified approach to diagnostics, treatment, and prevention of these conditions. PMID:27172721

  14. Urantide alleviates monocrotaline induced pulmonary arterial hypertension in Wistar rats.

    PubMed

    Mei, Yifang; Jin, Hong; Tian, Wei; Wang, Hao; Wang, Han; Zhao, Yanping; Zhang, Zhiyi; Meng, Fanchao

    2011-08-01

    Pulmonary arterial hypertension (PAH) is a serious disorder with poor prognosis. Urotensin II (UII) has been confirmed to be powerful vasoconstrictor than endothelin-1, which may play an important role in PAH development. The aim of this study is to observe the effects of urantide, a UII receptor antagonist, on monocrotaline (MCT) induced PAH in rats. 60 male Wistar rats were divided into six groups. For early treatment experiment, rats were divided into normal control group, MCT(4w) model group (MCT + saline × 3 wks from the 8th day of MCT injection) and urantide early treatment group (MCT + urantide 10 μg/kg/d × 3 wks, 1 week after MCT injection once). For late treatment experiment, rats were divided as controls, MCT(6w) model group (MCT + saline × 2 wks, 4 weeks after MCT injection once) and urantide late treatment group (MCT + urantide 10 μg/kg/d × 2 wks, 4 weeks after MCT injection once). At the end of experiments, mean pulmonary arterial pressures (mPAP) and mean blood pressure (MBP) of rats in each group were measured by catheterization. Right ventricular weight ratio was also weighed. Relaxation effects of urantide on intralobar pulmonary arterial rings of normal control and MCT(4w) model rats were investigated. Pulmonary artery remodeling was detected by hematoxylin and eosin (HE) staining and immunohistochemistry analysis. Serum nitric oxide (NO) levels in all six groups were assayed by ELISA kits. Urantide markedly reduced the mPAP levels of MCT induced PAH in both early and late treatment groups. It didn't change the MBP. Urantide dose-dependently relaxed the pulmonary arterial rings of normal control and MCT(4w) model rats. Moreover, N(G)-Nitro-l-arginine Methyl Ester (l-NAME) blocked the dilation response induced by urantide. In addition, urantide inhibited the pulmonary vascular remodeling remarkably. Serum NO level elevated in both early and late treatment rats with urantide infusion. These results suggest that urantide effectively alleviated

  15. [Clinical guidelines for detection, prevention, diagnosis and treatment of systemic arterial hypertension in Mexico (2008)].

    PubMed

    Rosas, Martín; Pastelín, Gustavo; Vargas-Alarcón, Gilberto; Martínez-Reding, Jesús; Lomelí, Catalina; Mendoza-González, Celso; Lorenzo, José Antonio; Méndez, Arturo; Franco, Martha; Sánchez-Lozada, Laura Gabriela; Verdejo, Juan; Sánchez, Noé; Ruiz, Rocío; Férez-Santander, Sergio Mario; Attie, Fause

    2008-01-01

    The multidisciplinary Institutional Committee of experts in Systemic Arterial Hypertension from the National Institute of Cardiology "Ignacio Chávez" presents its update (2008) of "Guidelines and Recommendations" for the early detection, control, treatment and prevention of Hypertension. The boarding tries to be simple and realistic for all that physicians whom have to face the hypertensive population in their clinical practice. The information is based in the most recent scientific evidence. These guides are principally directed to hypertensive population of emergent countries like Mexico. It is emphasized preventive health measures, the importance of the no pharmacological actions, such as good nutrition, exercise and changes in life style, (which ideally it must begin from very early ages). "We suggest that the changes in the style of life must be vigorous, continuous and systematized, with a real reinforcing by part of all the organisms related to the health education for all population (federal and private social organisms). It is the most important way to confront and prevent this pandemic of chronic diseases". In this new edition the authors amplifies the information and importance on the matter. The preventive cardiology must contribute in multidisciplinary entailment. Based mainly on national data and the international scientific publications, we developed our own system of classification and risk stratification for the carrying people with hypertension, Called HTM (Arterial Hypertension in Mexico) index. Its principal of purpose this index is to keep in mind that the current approach of hypertension must be always multidisciplinary. The institutional committee of experts reviewed with rigorous methodology under the principles of the evidence-based medicine, both, national and international medical literature, with the purpose of adapting the concepts and guidelines for a better control and treatment of hypertension in Mexico. This work group recognizes

  16. Macitentan (Opsumit) for the treatment of pulmonary arterial hypertension.

    PubMed

    Clarke, Megan; Walter, Claire; Agarwal, Richa; Kanwar, Manreet; Benza, Raymond L

    2014-07-01

    The endothelin pathway is a key pathway for the pathogenesis of pulmonary arterial hypertension (PAH). Antagonism of this pathway is recommended as initial therapy in low-risk patient with PAH to inhibit fibrosis, cell proliferation, and inflammation caused by endothelin. Prior to October 2013, ambrisentan, a selective ETA receptor antagonist and bosentan, a dual ETA/ETB antagonist, were the only currently available agents for PAH targeting the endothelin pathway. Based on the results of the SERAPHIN trial, macitentan (brand name Opsumit®), a new ETA/ETB antagonist, has been US FDA approved to delay disease progression and reduce hospitalizations for PAH. SERAPHIN is the first ERA trial to use an event-driven strategy with a composite primary end point of morbidity or mortality. Previous trials have focused on short-term outcomes, such as improved 6-min walk distance and WHO functional class. PMID:24851934

  17. Pathways in pulmonary arterial hypertension: the future is here.

    PubMed

    Sitbon, Olivier; Morrell, Nicholasw

    2012-12-01

    It is well established that the endothelin, nitric oxide and prostacyclin pathways play an important role in the development of pulmonary arterial hypertension (PAH). Indeed, the therapeutic options currently available for the management of PAH all act on one of these mechanistic pathways. However, this is an exciting time for both clinicians and scientists, as increased understanding of the mechanisms involved in the pathogenesis and progression of PAH has resulted in the development of a number of novel therapeutic options. This article highlights how the introduction of new compounds such as macitentan, riociguat and selexipag, which act on the endothelin, nitric oxide and prostacyclin pathways, respectively, have the potential to further improve the prognosis for patients with PAH. PMID:23204120

  18. Selexipag for the treatment of pulmonary arterial hypertension.

    PubMed

    Sharma, Kamal

    2016-01-01

    The endothelin (ET), nitric oxide (NO) and prostacyclin (PGI2) pathways are involved in pulmonary arterial hypertension (PAH) pathogenesis. While ET and NO are targeted early in the disease process, limitations of current pharmacotherapies that target the PGI2 pathway (PGI2 or PGI2 analogues) result in them not being used or delayed. Selexipag is a novel oral, selective agonist of the PGI2 (IP) receptor. Activation of the IP receptor induces vasodilation in the pulmonary circulation and inhibits the proliferation of vascular smooth muscle cells, key factors in PAH pathogenesis. By combining oral dosing with improved receptor selectivity, selexipag may enable earlier combination therapy targeting the three-molecular pathways of PAH with anticipated improvements in daily- and long-term clinical function and outcome in PAH. PMID:26567613

  19. An update on medical therapy for pulmonary arterial hypertension.

    PubMed

    Wu, Yan; O'Callaghan, Dermot S; Humbert, Marc

    2013-12-01

    Over the past 20 years, great progress has been made in the treatment of pulmonary arterial hypertension (PAH). Available therapies target one of three principal pathways: the endothelin (ET), nitric oxide (NO) or the prostacyclin (PGI2) pathway. Evidence shows that current drugs, used either as monotherapy or in different combinations, can improve exercise capacity, clinical symptoms, hemodynamics and even survival in PAH. Unfortunately, the disease remains incurable and the prognosis of the disease is still poor. However, existing and novel potent antiproliferative therapies are being explored, and new agents targeting different and/or additional pathways are likely to become available to clinicians in the near future. Promising candidates include tyrosine kinase antagonists (e.g. imatinib); soluble guanylate cyclase stimulators (riociguat); an oral analog of prostacyclin (selexipag); and a tissue targeting endothelin receptor antagonist (macitentan). Phase II or III trials have either been completed or are underway to evaluate the safety and efficacy of these various therapies. PMID:24122306

  20. The role of endothelin-1 in pulmonary arterial hypertension

    PubMed Central

    Chester, Adrian H.; Yacoub, Magdi H.

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a rare but debilitating disease, which if left untreated rapidly progresses to right ventricular failure and eventually death. In the quest to understand the pathogenesis of this disease differences in the profile, expression and action of vasoactive substances released by the endothelium have been identified in patients with PAH. Of these, endothelin-1 (ET-1) is of particular interest since it is known to be an extremely powerful vasoconstrictor and also involved in vascular remodelling. Identification of ET-1 as a target for pharmacological intervention has lead to the discovery of a number of compounds that can block the receptors via which ET-1 mediates its effects. This review sets out the evidence in support of a role for ET-1 in the onset and progression of the disease and reviews the data from the various clinical trials of ET-1 receptor antagonists for the treatment of PAH. PMID:25405182

  1. Pulmonary arterial hypertension: on the way to a manageable disease.

    PubMed

    Mucke, Hermann A M

    2008-09-01

    Pulmonary arterial hypertension (PAH) is an orphan disease for which no specific pharmacological therapy was available until 1996. Pharmacotherapy for PAH is currently dominated by three endothelin receptor antagonists, bosentan, ambrisentan and sitaxentan (which is not yet approved in the US), and the PDE5 inhibitor sildenafil. Drug candidates undergoing phase III clinical trials for PAH include inhalable and oral treprostinil, aviptadil (an inhalable vasoactive intestinal peptide), and the PDE5 inhibitor tadalafil. Riociguat, a soluble guanylate cyclase stimulator, is scheduled to enter phase III clinical trials in 2008. By approximately 2010, the role of infusable or injectable PGs as treatment for PAH will likely diminish significantly, while inhalable nitric oxide will remain as mainstay therapy in neonatal PAH. Benefits in survival and quality-of-life will decide if any of the more experimental approaches that utilize newly discovered molecular pathways in PAH will ultimately result in marketed drugs. PMID:18729002

  2. New Trial Designs and Potential Therapies for Pulmonary Artery Hypertension

    PubMed Central

    Gomberg-Maitland, Mardi; Bull, Todd M.; Saggar, Rajeev; Barst, Robyn J.; Elgazayerly, Amany; Fleming, Thomas R.; Grimminger, Friedrich; Rainisio, Maurizio; Stewart, Duncan J.; Stockbridge, Norman; Ventura, Carlo; Ghofrani, Ardeschir H.; Rubin, Lewis J.

    2014-01-01

    A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH. PMID:24355645

  3. Connective tissue disease-related pulmonary arterial hypertension.

    PubMed

    Thakkar, Vivek; Lau, Edmund M T

    2016-02-01

    Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH. PMID:27421214

  4. Psychosocial Burdens of Pulmonary Arterial Hypertension: A Discussion Paper.

    PubMed

    Doyle-Cox, Carolyn; Brousseau, Carolynne; Tulloch, Heather; Mielniczuk, Lisa M; Davies, Ross A; Sherrard, Heather; Clark, Lorraine

    2016-01-01

    Pulmonary arterial hypertension is an uncommon and devastating chronic illness with no known cure. Little is known about the disease, and even less about the psychosocial burdens. While it is important to create awareness about the physical aspects of the disease, it is equally important to create awareness about the psychosocial burdens patients and their families face. We reviewed the literature to better understand these psychosocial burdens, which include impact from physical limitations, emotional strains, financial burdens, social isolation, lack of intimacy in relationships, and an overall lack of information. The findings can be used to assist health care providers to understand the psychosocial challenges that are being experienced by patients and families in order to better provide supportive care. The creation of a standardized tool to assess the psychosocial burdens at each clinic visit can benefit health care providers by addressing challenges faced and facilitate subsequent referral to appropriate specialists. PMID:27159936

  5. Optimising the management of pulmonary arterial hypertension patients: emergency treatments.

    PubMed

    Delcroix, M; Naeije, R

    2010-09-01

    Pulmonary arterial hypertension (PAH) is a rare and potentially fatal disease whose management is usually restricted to a few specialised centres. As patients do not necessarily live in the neighbourhood of these centres, daily care and emergencies have to be delegated to first and second lines. Treatment guidelines do not usually provide recommendations for acute emergency situations as evidence is scarce. This short review provides a description of our therapeutic protocols based on available data. A model of transmural organisation of care for PAH patients, currently applied in Belgium, is described. Thereafter, based on an analysis of the reasons of death in the PAH population, a review of the main emergencies is provided. Cardiac arrest and resuscitation, decompensated right heart failure, respiratory failure, arrhythmia, pericardial effusion, haemoptysis, surgery and drug-related adverse events will be discussed successively. Case reports showing the precariousness of PAH patients will enforce our thesis of the need for optimal patient management organisation. PMID:20956193

  6. [Risk assessment of arterial hypertension in a working population].

    PubMed

    Montalti, M; Bargiani, M; Montalti, B; Mucci, N; Cupelli, V; Arcangeli, G

    2012-01-01

    During last years life expectation and working-life are increased and, consequently, the evaluation of workers whit chronic age-related diseases is more frequent than in the previous decades. We analyzed 9616 (2337 females and 7279 males) medical reports collected during health surveillance. Workers with arterial hypertension were 1770 (254 females and 1516 males) with an average age of 49.02 years +/- 9.52, and an average BMI of 27.9 +/- 4.43 Kg/m_. Workers who reported a complete fitness-to-work certification were 88.6%, ones with a fitness-to-work certification whit limitations were 11.2%, and only 0.2% were unfit to work. Our data confirm the importance of company strategies oriented to health promotion on the workplaces considering the progressive ageing of the workforces. PMID:23405619

  7. [Successful pregnancy in a patient with idiopathic pulmonary arterial hypertension. Case report].

    PubMed

    Szenczi, Orsolya; Karlócai, Kristóf; Bucsek, László; Rigó, János

    2016-04-10

    Idiopathic pulmonary arterial hypertension is characterized by progressive increase in pulmonary arterial pressure and pulmonary vascular resistance which lead to right ventricular failure and death. Pregnancy in patients with idiopathic pulmonary arterial hypertension is contraindicated because of the high maternal and fetal mortality. The authors present a case of successful pregnancy and delivery of a patient with idiopathic pulmonary arterial hypertension in Hungary for the first time. The aim of the report was to demonstrate that management and treatment of idiopathic pulmonary arterial hypertension in a pregnant woman is a complex and multidisciplinary task that should involve obstetrician, cardiologist and anesthesiologist. Those patients who become pregnant and do not wish to terminate the pregnancy must be referred to obstetric centers where a multidiciplinary approach is taken. PMID:27039998

  8. Epigenetic modulation as a therapeutic approach for pulmonary arterial hypertension.

    PubMed

    Kim, Jun-Dae; Lee, Aram; Choi, Jihea; Park, Youngsook; Kang, Hyesoo; Chang, Woochul; Lee, Myeong-Sok; Kim, Jongmin

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH. PMID:26228095

  9. Epigenetic modulation as a therapeutic approach for pulmonary arterial hypertension

    PubMed Central

    Kim, Jun-Dae; Lee, Aram; Choi, Jihea; Park, Youngsook; Kang, Hyesoo; Chang, Woochul; Lee, Myeong-Sok; Kim, Jongmin

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a rare but progressive and currently incurable disease, which is characterized by vascular remodeling in association with muscularization of the arterioles, medial thickening and plexiform lesion formation. Despite our advanced understanding of the pathogenesis of PAH and the recent therapeutic advances, PAH still remains a fatal disease. In addition, the susceptibility to PAH has not yet been adequately explained. Much evidence points to the involvement of epigenetic changes in the pathogenesis of a number of human diseases including cancer, peripheral hypertension and asthma. The knowledge gained from the epigenetic study of various human diseases can also be applied to PAH. Thus, the pursuit of novel therapeutic targets via understanding the epigenetic alterations involved in the pathogenesis of PAH, such as DNA methylation, histone modification and microRNA, might be an attractive therapeutic avenue for the development of a novel and more effective treatment. This review provides a general overview of the current advances in epigenetics associated with PAH, and discusses the potential for improved treatment through understanding the role of epigenetics in the development of PAH. PMID:26228095

  10. Primary renal artery choriocarcinoma causing secondary renovascular hypertension

    PubMed Central

    Usta, Taner Abdullah; Karacan, Tolga; Ozyurek, Eser; Naki, M. Murat; Omeroglu, Suat Nail; Demirkiran, Fuat

    2014-01-01

    INTRODUCTION Choriocarcinoma is a rare primary germ cell tumour of the ovary composed of cyto- and syncytotrophoblast cells. Most of the choriocarcinomas are normally arising in the gestational trophoblast, gonads and, less frequently, mediastinum, pineal gland and retroperitoneum. PRESENTATION OF CASE We report a case of primary choriocarcinoma of renal artery causing secondary renovascular hypertension in a 28 years old woman of reproductive age, presenting with abdominal pain, minimal vaginal bleeding and a delayed menstrual period. DISCUSSION Non-gestational choriocarcinomas, are histologically related to the pregnancy related gestational choriocarcinomas. These two subtypes may have to be differentiated according the clinical and radiological findings and DNA analysis may be used for this purpose as well. In many studies, authors have stated that nongestational choriocarcinoma diagnosis could be implemented in situations where the presence of a pregnancy could not be considered like the prepubertal period. CONCLUSION Choriocarcinoma should as well be considered among the possibilities in the differential diagnosis of the causes for secondary hypertension, especially within a picture of pregnancy of unknown location, albeit being one of the rarest. PMID:25437675

  11. Hemodynamic Characterization of Rodent Models of Pulmonary Arterial Hypertension.

    PubMed

    Ma, Zhiyuan; Mao, Lan; Rajagopal, Sudarshan

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a rare disease of the pulmonary vasculature characterized by endothelial cell apoptosis, smooth muscle proliferation and obliteration of pulmonary arterioles. This in turn results in right ventricular (RV) failure, with significant morbidity and mortality. Rodent models of PAH, in the mouse and the rat, are important for understanding the pathophysiology underlying this rare disease. Notably, different models of PAH may be associated with different degrees of pulmonary hypertension, RV hypertrophy and RV failure. Therefore, a complete hemodynamic characterization of mice and rats with PAH is critical in determining the effects of drugs or genetic modifications on the disease. Here we demonstrate standard procedures for assessment of right ventricular function and hemodynamics in both rat and mouse PAH models. Echocardiography is useful in determining RV function in rats, although obtaining standard views of the right ventricle is challenging in the awake mouse. Access for right heart catheterization is obtained by the internal jugular vein in closed-chest mice and rats. Pressures can be measured using polyethylene tubing with a fluid pressure transducer or a miniature micromanometer pressure catheter. Pressure-volume loop analysis can be performed in the open chest. After obtaining hemodynamics, the rodent is euthanized. The heart can be dissected to separate the RV free wall from the left ventricle (LV) and septum, allowing an assessment of RV hypertrophy using the Fulton index (RV/(LV+S)). Then samples can be harvested from the heart, lungs and other tissues as needed. PMID:27167679

  12. Epigenetics and arterial hypertension: the challenge of emerging evidence.

    PubMed

    Friso, Simonetta; Carvajal, Cristian A; Fardella, Carlos E; Olivieri, Oliviero

    2015-01-01

    Epigenetic phenomena include DNA methylation, post-translational histone modifications, and noncoding RNAs, as major marks. Although similar to genetic features of DNA for their heritability, epigenetic mechanisms differ for their potential reversibility by environmental and nutritional factors, which make them potentially crucial for their role in complex and multifactorial diseases. The function of these mechanisms is indeed gaining interest in relation to arterial hypertension (AH) with emerging evidence from cell culture and animal models as well as human studies showing that epigenetic modifications have major functions within pathways related to AH. Among epigenetic marks, the role of DNA methylation is mostly highlighted given the primary role of this epigenetic feature in mammalian cells. A lower global methylation was observed in DNA of peripheral blood mononuclear cells of hypertensive patients. Moreover, DNA hydroxymethylation appears modifiable by salt intake in a Dahl salt-sensitive rat model. The specific function of DNA methylation in regulating the expression of AH-related genes at promoter site was described for hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2), somatic angiotensin converting enzyme (sACE), Na+/K+/2Cl- cotransporter 1 (NKCC1), angiotensinogen (AGT), α-adducin (ADD1), and for other crucial genes in endocrine hypertension. Post-translational histone methylation at different histone 3 lysine residues was also observed to control the expression of genes related to AH as lysine-specific demethylase-1(LSD1), HSD11B2, and epithelial sodium channel subunit α (SCNN1A). Noncoding RNAs including several microRNAs influence genes involved in steroidogenesis and the renin-angiotensin-aldosterone pathway. In the present review, the current knowledge on the relationship between the main epigenetic marks and AH will be presented, considering the challenge of epigenetic patterns being modifiable by environmental factors that may lead toward

  13. Renovascular hypertension

    MedlinePlus

    Renal hypertension; Hypertension - renovascular; Renal artery occlusion; Stenosis - renal artery; Renal artery stenosis ... Renal artery stenosis is a narrowing or blockage of the arteries that supply blood to the kidneys. The most ...

  14. Comparative Effectiveness of Oral Medications for Pulmonary Arterial Hypertension.

    PubMed

    Igarashi, Ataru; Inoue, Sachie; Ishii, Tomonori; Tsutani, Kiichiro; Watanabe, Hiroshi

    2016-07-27

    Pulmonary arterial hypertension (PAH) is a disease that imposes a significant burden on patients. Although multiple treatment options for PAH are available, head-to-head comparisons are difficult to conduct. Network meta-analysis (NMA) can be a useful alternative for direct comparison to estimate the relative effectiveness of multiple treatments. The objective of the present study was to conduct a systematic review and NMA to evaluate the relative effectiveness among oral PAH medications.Data collection was performed by searching the Cochrane Central Register of Controlled Trials (CENTRAL) and Ichushi-Web. Randomized controlled trials (RCTs) assessing at least 1 of the following 3 outcome measurements; 6-minute walk distance test (6MWD), WHO functional class (WHOFC), and mean pulmonary artery pressure (mPAP) were included (PROSPERO registration number: CRD42015016557). Outcomes were evaluated by estimating the differences in the mean change from baseline or by estimating the odds ratios. Analyses were performed using WinBUGS 1.4.3.Seven double-blind RCTs were eligible. NMA results showed similar improvements in 6MWD for all medications assessed. Bosentan and sildenafil caused a statistically significant improvement in WHOFC compared to other medications.The relative effectiveness of oral PAH medications could be compared using NMA, which suggested the superiority of bosentan and sildenafil in the improvement of WHOFC. PMID:27385603

  15. Drug-induced pulmonary arterial hypertension: a recent outbreak.

    PubMed

    Montani, David; Seferian, Andrei; Savale, Laurent; Simonneau, Gérald; Humbert, Marc

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a rare disorder characterised by progressive obliteration of the pulmonary microvasculature resulting in elevated pulmonary vascular resistance and premature death. According to the current classification PAH can be associated with exposure to certain drugs or toxins, particularly to appetite suppressant intake drugs, such as aminorex, fenfluramine derivatives and benfluorex. These drugs have been confirmed to be risk factors for PAH and were withdrawn from the market. The supposed mechanism is an increase in serotonin levels, which was demonstrated to act as a growth factor for the pulmonary artery smooth muscle cells. Amphetamines, phentermine and mazindol were less frequently used, but are considered possible risk factors, for PAH. Dasatinib, dual Src/Abl kinase inhibitor, used in the treatment of chronic myelogenous leukaemia was associated with cases of severe PAH, potentially in part reversible after dasatinib withdrawal. Recently, several studies have raised the issue of potential endothelial dysfunction that could be induced by interferon, and a few cases of PAH have been reported with interferon therapy. PAH remains a rare complication of these drugs, suggesting possible individual susceptibility, and further studies are needed to identify patients at risk of drug-induced PAH. PMID:23997051

  16. Peripheral airways obstruction in idiopathic pulmonary artery hypertension (primary).

    PubMed

    Fernandez-Bonetti, P; Lupi-Herrera, E; Martinez-Guerra, M L; Barrios, R; Seoane, M; Sandoval, J

    1983-05-01

    The mechanical properties of the lung were studied in ten nonsmokers with idiopathic pulmonary artery hypertension (IPAH) (mean pulmonary artery pressure 65.7 +/- 30 mm Hg). In the routine lung test, residual volume was found to be abnormal (greater than 120 percent of the predicted) in seven patients, and measured airway resistance was normal in eight out of the ten patients. A decreased FEF 75-85 percent, abnormal values for the helium-air flow ratios and increased closing capacities were documented in eight of ten patients in whom lung elastic recoil was normal (six of ten) or increased (four of ten). These features suggest peripheral airways obstruction (PAO) which was also supported by histopathologic findings in three cases (one biopsy and two necropsies). The observed changes in lung compliance could be related to the behavior of the coupling of the air-space and vascular compartments. The etiology of PAO in IPAH patients is not known, but our results indicate that both the peripheral airways and the pulmonary circulation are affected. The knowledge of PAO in IPAH patients could help to better understand the observed V/Q inequality in this entity. PMID:6839814

  17. The limits of oral therapy in pulmonary arterial hypertension management

    PubMed Central

    Liu, Qian-Qian; Jing, Zhi-Cheng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a devastating disease in which remodeling of the small pulmonary arteries leads to a progressive increase in pulmonary vascular resistance and right-sided heart failure. Over the past decade, new treatments for PAH, such as the use of ERAs, PDE-5 inhibitors and prostacyclin analogs, have brought about dramatic improvements in clinical outcomes. Epoprostenol infusion therapy has been shown to improve hemodynamics, functional status, and survival, and it remains the gold standard for treatment of patients with severe PAH. Many agents, approved for PAH are always delivered in pill form. Although oral therapy occupies an important position, it has some drawbacks and limitations in PAH management. For patients in World Health Organization functional class IV and with severe right heart failure, there are few data on the long-term survival of patients treated with oral medications. Further research, exploration, and clinical experience with oral therapy in severe PAH and combination therapy will redefine its position in PAH management. PMID:26648729

  18. Signal transduction in the development of pulmonary arterial hypertension

    PubMed Central

    Malenfant, Simon; Neyron, Anne-Sophie; Paulin, Roxane; Potus, François; Meloche, Jolyane; Provencher, Steeve; Bonnet, Sébastien

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a unique disease. Properly speaking, it is not a disease of the lung. It can be seen more as a microvascular disease occurring mainly in the lungs and affecting the heart. At the cellular level, the PAH paradigm is characterized by inflammation, vascular tone imbalance, pulmonary arterial smooth muscle cell proliferation and resistance to apoptosis and the presence of in situ thrombosis. At a clinical level, the aforementioned abnormal vascular properties alter physically the pulmonary circulation and ventilation, which greatly influence the right ventricle function as it highly correlates with disease severity. Consequently, right heart failure remains the principal cause of death within this cohort of patients. While current treatment modestly improve patients’ conditions, none of them are curative and, as of today, new therapies are lacking. However, the future holds potential new therapies that might have positive influence on the quality of life of the patient. This article will first review the clinical presentation of the disease and the different molecular pathways implicated in the pathobiology of PAH. The second part will review tomorrow's future putative therapies for PAH. PMID:24015329

  19. Treatment of pulmonary arterial hypertension in connective tissue disease.

    PubMed

    Grünig, Ekkehard

    2012-05-28

    Pulmonary arterial hypertension (PAH) is a group of distinct disorders that includes idiopathic PAH (IPAH), familial PAH and PAH associated with other conditions (APAH) such as connective tissue disease (CTD-APAH) or congenital heart disease. PAH is characterized by increased pulmonary arterial pressure and pulmonary vascular resistance. If left untreated, PAH can lead to right heart failure and premature death. CTD-APAH represents an important clinical subgroup of APAH that has a higher risk of death than IPAH. The European treatment guidelines advocate the use of PAH-targeted therapies including bosentan, ambrisentan, sildenafil, inhaled iloprost, intravenous epoprostenol (I-A recommendations), tadalafil or treprostinil (I-B recommendations) for patients in WHO functional class II-III. Not all randomized clinical studies of the approved PAH-targeted therapies have included patients with CTD-APAH. The purpose of this review is to describe the clinical characteristics of CTD-APAH and discuss the approved pharmacological treatments, with a focus on data specific to this subgroup where possible. PMID:22621693

  20. Functional Prostacyclin Synthase Promoter Polymorphisms. Impact in Pulmonary Arterial Hypertension

    PubMed Central

    Cornelius, Amber R.; Lu, Xiao; Conklin, David S.; Del Rosario, Mark J.; Lowe, Anita M.; Elos, Mihret T.; Fettig, Lynsey M.; Wong, Randall E.; Hara, Naoko; Cogan, Joy D.; Phillips, John A.; Taylor, Matthew R.; Graham, Brian B.; Tuder, Rubin M.; Loyd, James E.; Geraci, Mark W.

    2014-01-01

    Rationale: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary artery pressure, vascular remodeling, and ultimately right ventricular heart failure. PAH can have a genetic component (heritable PAH), most often through mutations of bone morphogenetic protein receptor 2, and idiopathic and associated forms. Heritable PAH is not completely penetrant within families, with approximately 20% concurrence of inactivating bone morphogenetic protein receptor 2 mutations and delayed onset of PAH disease. Because one of the treatment options is using prostacyclin analogs, we hypothesized that prostacyclin synthase promoter sequence variants associated with increased mRNA expression may play a protective role in the bone morphogenetic protein receptor 2 unaffected carriers. Objectives: To characterize the range of prostacyclin synthase promoter variants and assess their transcriptional activities in PAH-relevant cell types. To determine the distribution of prostacyclin synthase promoter variants in PAH, unaffected carriers in heritable PAH families, and control populations. Methods: Polymerase chain reaction approaches were used to genotype prostacyclin synthase promoter variants in more than 300 individuals. Prostacyclin synthase promoter haplotypes’ transcriptional activities were determined with luciferase reporter assays. Measurements and Main Results: We identified a comprehensive set of prostacyclin synthase promoter variants and tested their transcriptional activities in PAH-relevant cell types. We demonstrated differences of prostacyclin synthase promoter activities dependent on their haplotype. Conclusions: Prostacyclin synthase promoter sequence variants exhibit a range of transcriptional activities. We discovered a significant bias for more active prostacyclin synthase promoter variants in unaffected carriers as compared with affected patients with PAH. PMID:24605778

  1. Imatinib in pulmonary arterial hypertension: c-Kit inhibition.

    PubMed

    Farha, Samar; Dweik, Raed; Rahaghi, Franck; Benza, Raymond; Hassoun, Paul; Frantz, Robert; Torres, Fernando; Quinn, Deborah A; Comhair, Suzy; Erzurum, Serpil; Asosingh, Kewal

    2014-09-01

    Pulmonary arterial hypertension (PAH) is a progressive disease characterized by severe remodeling of the pulmonary artery resulting in increased pulmonary artery pressure and right ventricular hypertrophy and, ultimately, failure. Bone marrow-derived progenitor cells play a critical role in vascular homeostasis and have been shown to be involved in the pathogenesis of PAH. A proliferation of c-Kit(+) hematopoietic progenitors and mast cells has been noted in the remodeled vessels in PAH. Imatinib, a tyrosine kinase inhibitor that targets c-Kit, has been shown to be beneficial for patients with PAH. Here we hypothesize that the clinical benefit of imatinib in PAH could be related to c-Kit inhibition of progenitor cell mobilization and maturation into mast cells. As a corollary to the phase 3 study using imatinib in PAH, blood samples were collected from 12 patients prior to starting study drug (baseline) and while on treatment at weeks 4 and 24. Eight were randomized to imatinib and 4 to placebo. Circulating c-Kit(+) and CD34(+)CD133(+) hematopoietic progenitors as well as biomarkers of mast cell numbers and activation were measured. Circulating CD34(+)CD133(+) and c-Kit(+) progenitor cells as well as c-Kit(+)/CD34(+)CD133(+) decreased with imatinib therapy (all P < 0.05). In addition, total tryptase, a marker of mast cell load, dropped with imatinib therapy (P = 0.02) and was related to pulmonary vascular resistance (R = 0.7, P = 0.02). The findings support c-Kit inhibition as a potential mechanism of action of imatinib in PAH and suggest that tryptase is a potential biomarker of response to therapy. PMID:25621158

  2. [Endovascular radiofrequency denervation of renal arteries as an innovation method of treatment of refractory arterial hypertension. First experience in Russia].

    PubMed

    Danilov, N M; Matchin, Iu G; Chazova, I E

    2012-01-01

    Excessive activation of the sympathetic nervous system forms the basis of pathogenesis of essential arterial hypertension (AH). The present work was aimed at evaluating efficacy and safety of endovascular radiofrequency denervation of renal arteries in patients with AH refractory AH based on the initial first experience in with using this methodology in the Russian Federation. The interventions were carried out on December 14-15th, 2011 in the first five patients presenting with AH refractory to antihypertensive therapy consisting of three and more drugs in therapeutic doses, one of which was a diuretic. The selection criteria were systolic arterial pressure (SAP) ≥160 mm Hg or ≥150 mm Hg in the presence of type 2 diabetes mellitus. The obligatory conditions for selection were the preserved renal function [glomerular filtration rate (GFR) ≥45 ml/min] and the absence of the secondary form of AH. The procedure of denervation was performed in the conditions of roentgen-operating room using special Medtronic Ardian Simplicity Catheter System™. In all cases we managed to perform bilateral denervation of renal arteries with the radiofrequency effect in not less than 4 zones of each of vessels. Efficacy of each of the effect was registered with due regard for reaching certain temperature and values of impedance. The interventions were not accompanied by the development of any complications either in the area of manipulations or the site of puncture. Neither were there any complications from the side of the cardiovascular or excretory systems of the body. Diurnal monitoring of AP (DMAP) registered a significant decrease in SAP averagely from 174±12 to 145±10 mm Hg three days after the intervention. A persistent antihypertensive effect was confirmed by the DMAP findings one month after denervation - the SAP level averagely amounted to 131±6 mm Hg. Endovascular radiofrequency denervation of renal arteries is a safe and efficient method of treatment of AH resistant

  3. Pulmonary arterial hypertension in patients with sarcoidosis: the Pulsar single center experience.

    PubMed

    Pabst, Stefan; Hammerstingl, Christoph; Grau, Natalie; Kreuz, Jens; Grohe, Christian; Juergens, Uwe R; Nickenig, Georg; Skowasch, Dirk

    2013-01-01

    Sarcoidosis is a systemic granulomatous disease with unknown etiology. Lungs and lymph nodes are commonly affected. Also, cases of pulmonary hypertension (PH) and pulmonary arterial hypertension (PAH) are described. However, the exact prevalence of PAH in patients with sarcoidosis is unclear. A 111 patients with proven sarcoidosis were recruited from January 2010 to October 2010. All patients were studied prospectively by transthoracic echocardiography (TTE) for the presence of PH. In assumed PH, a right heart catheterization (RHC) followed if there were no other reasons for PH. In 23 of the 111 patients (21%) PH was assumed in TTE. Three patients presented with severe mitral insufficiency III° and IV°, in eight patients PH was supposed to be caused by chronic heart failure or relevant diastolic dysfunction > II°, two patients declined undergoing RHC. Of the ten patients investigated with RHC, four showed a precapillary pulmonary arterial hypertension and in one patient a postcapillary hypertension was diagnosed. All four patients with precapillary PH had a radiologic stage III and IV. In three of the four patients a significantly reduced transfer factor for carbon monoxide (TLCO) <50% was found. All patients with precapillary PH had a chronic course of sarcoidosis lasting ≥13 years. This is the first study which prospectively investigated a large cohort of patients with sarcoidosis for the prevalence of PH and PAH. The prevalence of precapillary PH was found to be at least 3.6% (4/111) and therefore exceeds the prevalence of PAH in the normal population by far. A chronic and progressive lung involvement due to sarcoidosis seems to be the most evident risk factor for developing a sarcoidosis PH. PMID:22826080

  4. Inhibition of Excessive Cell Proliferation by Calcilytics in Idiopathic Pulmonary Arterial Hypertension

    PubMed Central

    Yamamura, Aya; Ohara, Naoki; Tsukamoto, Kikuo

    2015-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease of unknown pathogenesis. Vascular remodeling due to excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) is a critical pathogenic event that leads to early morbidity and mortality. The excessive cell proliferation is closely linked to the augmented Ca2+ signaling in PASMCs. More recently, we have shown by an siRNA knockdown method that the Ca2+-sensing receptor (CaSR) is upregulated in PASMCs from IPAH patients, involved in the enhanced Ca2+ response and subsequent excessive cell proliferation. In this study, we examined whether pharmacological blockade of CaSR attenuated the excessive proliferation of PASMCs from IPAH patients by MTT assay. The proliferation rate of PASMCs from IPAH patients was much higher (~1.5-fold) than that of PASMCs from normal subjects and patients with chronic thromboembolic pulmonary hypertension (CTEPH). Treatment with NPS2143, an antagonist of CaSR or calcilytic, clearly suppressed the cell proliferation in a concentration-dependent manner (IC50 = 2.64 μM) in IPAH-PASMCs, but not in normal and CTEPH PASMCs. Another calcilytic, Calhex 231, which is structurally unrelated to NPS2143, also concentration-dependently inhibited the excessive proliferation of IPAH-PASMCs (IC50 = 1.89 μM). In contrast, R568, an activator of CaSR or calcimimetic, significantly facilitated the proliferation of IPAH-PASMCs (EC50 = 0.33 μM). Similar results were obtained by BrdU incorporation assay. These results reveal that the excessive PASMC proliferation was modulated by pharmacological tools of CaSR, showing us that calcilytics are useful for a novel therapeutic approach for pulmonary arterial hypertension. PMID:26375676

  5. Association of Parental Hypertension With Arterial Stiffness in Nonhypertensive Offspring: The Framingham Heart Study.

    PubMed

    Andersson, Charlotte; Quiroz, Rene; Enserro, Danielle; Larson, Martin G; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Benjamin, Emelia J; Mitchell, Gary F; Vasan, Ramachandran S

    2016-09-01

    High arterial stiffness seems to be causally involved in the pathogenesis of hypertension. We tested the hypothesis that offspring of parents with hypertension may display higher arterial stiffness before clinically manifest hypertension, given that hypertension is a heritable condition. We compared arterial tonometry measures in a sample of 1564 nonhypertensive Framingham Heart Study third-generation cohort participants (mean age: 38 years; 55% women) whose parents were enrolled in the Framingham Offspring Study. A total of 468, 715, and 381 participants had 0 (referent), 1, and 2 parents with hypertension. Parental hypertension was associated with greater offspring mean arterial pressure (multivariable-adjusted estimate=2.9 mm Hg; 95% confidence interval, 1.9-3.9, and 4.2 mm Hg; 95% confidence interval, 2.9-5.5, for 1 and 2 parents with hypertension, respectively; P<0.001 for both) and with greater forward pressure wave amplitude (1.6 mm Hg; 95% confidence interval, 0.6-2.7, and 1.9 mm Hg; 95% confidence interval, 0.6-3.2, for 1 and 2 parents with hypertension, respectively; P=0.003 for both). Carotid-femoral pulse wave velocity and augmentation index displayed similar dose-dependent relations with parental hypertension in sex-, age-, and height-adjusted models, but associations were attenuated on further adjustment. Offspring with at least 1 parent in the upper quartile of augmentation index and carotid-femoral pulse wave velocity had significantly higher values themselves (P≤0.02). In conclusion, in this community-based sample of young, nonhypertensive adults, we observed greater arterial stiffness in offspring of parents with hypertension. These observations are consistent with higher vascular stiffness at an early stage in the pathogenesis of hypertension. PMID:27456526

  6. Severe pulmonary arterial hypertensive rats are tolerant to mild exercise

    PubMed Central

    Hartman, Lauren J.; Scruggs, April K.; McLendon, Jared M.; Haven, April K.; Bauer, Natalie N.

    2015-01-01

    Abstract A frequently used end point of clinical outcomes in patients with pulmonary arterial hypertension (PAH) is the 6-minute walk distance. Furthermore, some data suggest that mild to moderate exercise as an intervention in stable PAH is beneficial. Some of these questions have been recapitulated in the monocrotaline and hypoxia animal models of pulmonary hypertension. However, mild exercise and walk distance as end points have not been rigorously examined in the severe progressive Sugen 5416/hypoxia/normoxia (Su/Hx/Nx) animal model of PAH at each stage of worsening disease. Our hypothesis was that animals that were preselected as runners would have increased walk times and improved right ventricle/left ventricle plus septum (RV/LV+S) ratios, echocardiography, and histology compared with nonexercised Su/Hx/Nx animals. We examined four groups of rats: Su/Hx/Nx sedentary, Su/Hx/Nx exercised, control sedentary, and control exercised. Echocardiography was performed at 5, 8, and 13 weeks to assess right ventricular inner diameter in diastole and left ventricular eccentricity index. We found no difference between exercised and sedentary Su/Hx/Nx rats, and both were worsened compared with controls. Rats were euthanized at 13 weeks, and we found that neither RV/LV+S nor the occurrence of occlusive lesions were influenced by exercise. Most interesting, however, was that despite progressive PAH development, exercised Su/Hx/Nx rats showed no decrease in time or distance for treadmill exercise. In all, our data suggest that, despite severe PAH development, Su/Hx/Nx rats retain the same treadmill exercise capacity as control animals. PMID:26064461

  7. Drug treatment of pulmonary arterial hypertension: current and future agents.

    PubMed

    Hoeper, Marius M

    2005-01-01

    During the last decade we have witnessed substantial improvements in the therapeutic options for pulmonary arterial hypertension (PAH), including true innovations targeting some of the mechanisms involved in the pathogenesis of this devastating disease. Intravenous epoprostenol was the first drug to improve symptoms and survival of patients with PAH. Novel prostanoids, including subcutaneous treprostinil and inhaled iloprost, also have beneficial effects in many patients, although their long-term efficacy is less well known. Among the newer treatments for PAH, endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors have reshaped clinical practice. The endothelin receptor antagonist bosentan has been approved in many parts of the world and most current guidelines recommend this drug as first-line treatment for patients with PAH in functional class III. Novel endothelin receptor antagonists such as sitaxsentan sodium and ambrisentan are currently being investigated. The PDE5 sildenafil is also being intensively studied in patients with pulmonary hypertension, and most of the available data look promising, although approval for PAH is still pending. Other PDE5 inhibitors have not yet undergone extensive study in PAH. The increasing insight into the pathogenesis of PAH opens several new therapeutic opportunities, which include vasoactive intestinal peptide, selective serotonin reuptake inhibitors, adrenomedullin and HMG-CoA reductase inhibitors (statins). However, PAH is a complex disorder and targeting a single pathway can not be expected to be uniformly successful. Thus, combining substances with different modes of action is expected to improve symptoms, haemodynamics and survival in PAH patients, although combination therapy has yet to undergo the scrutiny of large randomised clinical trials. PMID:15977967

  8. Association of Hypertension With Erectile Function in Chronic Peripheral Arterial Insufficiency Patients

    PubMed Central

    Spessoto, Luis Cesar Fava; Facio, Fernando Nestor; de Arruda, Jose Germano Ferraz; Arruda, Pedro Francisco F.; Gatti, Marcio; Antoniassi, Thiago Silveira; Facio, Maria Fernanda Warick; de Godoy, Jose Maria Pereira

    2016-01-01

    Background Risk factors may influence the improvement or worsening of erectile dysfunction (ED). The aim of the current study was to evaluate the effect of systemic hypertension on ED in patients with peripheral arterial disease. Methods The effect of hypertension on ED was assessed in 125 consecutive patients in a cross-sectional quantitative study. The ages of the patients ranged from 19 to 88 years old (mean: 59.82 ± 10.48 years). The only exclusion criterion was the amputation of one or both legs. The ankle-arm index was assessed and the international index of ED questionnaire was applied to all participants in the study. Results Of the 125 patients, 22 (17.6%) had mild (grade 1), 50 (40.0%) had moderate (grade 2) and 53 (42.4%) had severe (grade 3) ED. Hypertensive patients have more ED, with ED in hypertensive patients being associated to chronic arterial disease. However, in comparison with normotensive patients, hypertension exerts an immediate protective effect on erectile function. Conclusions In conclusion, although erectile function is initially protected by systemic arterial hypertension in patients with chronic arterial disease, both chronic arterial disease and ED deteriorate over the long term in hypertensive patients. PMID:27429678

  9. Young Women with a Long Past of Resistant Hypertension Cured after Surgery of Severe Bilateral Ostial Renal Artery Stenosis.

    PubMed

    Simonnet, Blandine; Deharo, Pierre; Rouabah, Karim; Silhol, François; Soler, Raphael; Bartoli, Jean Michel; Lévrier, Olivier; Bartoli, Michel Alain; Magnan, Pierre Edouard; Sarlon-Bartoli, Gabrielle

    2016-07-01

    Fibromuscular dysplasia (FMD) is an underdiagnosed disease which can affect young people and with poor prognosis such as dissection or aneurysm rupture if unknown. This case illustrates a multi-vessel FMD with symptomatic severe bilateral ostial renal artery stenosis and intracranial aneurysms. One of the original features is a very late delay to diagnosis with 23 years between onset of hypertension and renal stenosis diagnosis, particularly due to lower quality of initial CT scan with milder and uncommon abnormalities. The experiment neuroradiologist had suspected the diagnosis of renal FMD because she developed intracranial aneurysms and he confirmed this diagnosis with an artery renal contrast injection during an intracranial angiogram Because of very tight and short stenosis, surgery was chosen for treatment and permitted the cure of hypertension, with normal home blood pressure after 6 months. Several particularities of FMD were presented in this case: important delay diagnosis due to rare lesion and lower sensitivity of CT in this form, the possibility to perform an angiography in high suspicion of FMD, poor prognosis risk with intracranial aneurisms and premature birth child, and the choice for surgery with cure of hypertension. We thought that hypertension etiologic evaluation must be repeated in case of resistant hypertension in young patients, particularly when they developed intracranial aneurysms. PMID:27174348

  10. Prevalence of chronic obstructive pulmonary disease among patients with systemic arterial hypertension without respiratory symptoms

    PubMed Central

    Rabahi, Marcelo Fouad; Pereira, Sheila Alves; Silva Júnior, José Laerte Rodrigues; de Rezende, Aline Pacheco; Castro da Costa, Adeliane; de Sousa Corrêa, Krislainy; Conde, Marcus Barreto

    2015-01-01

    Background The diagnosis of chronic obstructive pulmonary disease (COPD) is often delayed until later stages of the disease. The purpose of the present study was to determine the prevalence of COPD among adults on treatment for systemic arterial hypertension independently of the presence of respiratory symptoms. Methods This cross-sectional study included adults aged ≥40 years with tobacco/occupational exposure and systemic arterial hypertension diagnosed at three Primary Health Care facilities in Goiania, Brazil. Patients were evaluated using a standardized respiratory questionnaire and spirometry. COPD prevalence was measured considering the value of forced vital capacity and/or forced expiratory volume in 1 second <0.70. Results Of a total of 570 subjects, 316 (55%) met inclusion criteria and were invited to participate. Two hundred and thirty-three (73.7%) patients with arterial hypertension reported at least one respiratory symptom, while 83 (26.3%) reported no respiratory symptoms; 41 (17.6%) patients with arterial hypertension and at least one respiratory symptom, and 10 (12%) patients with arterial hypertension but no respiratory symptoms were diagnosed with COPD (P=0.24). The prevalence of COPD in people with no previous COPD diagnosis was greater among those with no respiratory symptoms (100%) than among those with respiratory symptoms (56.1%) (P=0.01). Conclusion Our findings suggest that regardless of the presence of respiratory symptoms, individuals aged ≥40 years with tobacco/occupational exposure and arterial hypertension may benefit from spirometric evaluation. PMID:26257517

  11. Arginase inhibition protects against hypoxia‑induced pulmonary arterial hypertension.

    PubMed

    Jiang, Wenjin; Sun, Bolin; Song, Xuepeng; Zheng, Yanbo; Wang, Ligang; Wang, Tao; Liu, Sheng

    2015-09-01

    The present study aimed to determine the role of arginase (Arg) in pulmonary arterial hypertension (PAH). In vitro, human pulmonary artery smooth muscle cells (HPASMCs) were cultured under hypoxic conditions with, or without, the Arg inhibitor, S‑(2‑boronoethyl)‑l‑cysteine (BEC), for 48 h, following which the proliferation of the HPASMCs was determined using MTT and cell counting assays. For the in vivo investigation, 30 male rats were randomly divided into the following three groups (n=10 per group): i) control group, ii) PAH group and iii) BEC group, in which the right ventricle systolic pressure (RVSP) of the rats was assessed. The levels of cyclin D1, cyclin‑dependent kinase (CDK)4 and p27 were measured in vitro and in vivo. The phosphorylation levels of Akt and extracellular‑related kinase (ERK) were also measured in HPASMCs. In vitro, compared with the hypoxia group, Arg inhibition reduced HPASMC proliferation and reduced the expression levels of cyclin D1, CDK4, phosphorylated (p‑)Akt and p‑ERK. By contrast, Arg inhibition increased the expression of p27. In vivo, compared with the control group, the expression levels of cyclin D1 and CDK4 were reduced in the PAH group, however, the expression of p27 and the RVSP increased. In the BEC group, the opposite effects were observed. Therefore, it was suggested that Arg inhibition may reduce the RVSP of PAH rats and reduce HPASMC proliferation by decreasing the expression levels of cyclin D1 and CDK4, increasing the expression of p27, and partly reducing the phosphorylation of Akt and ERK. PMID:26126810

  12. Are Hemodynamics Surrogate Endpoints in Pulmonary Arterial Hypertension?

    PubMed Central

    Ventetuolo, Corey E.; Gabler, Nicole B.; Fritz, Jason S.; Smith, K. Akaya; Palevsky, Harold I.; Klinger, James R.; Halpern, Scott D.; Kawut, Steven M.

    2014-01-01

    Background While frequently assessed in trials and clinical practice, hemodynamic response to therapy has never been validated as a surrogate endpoint for clinical events in pulmonary arterial hypertension (PAH). Methods and Results We performed a patient-level pooled analysis of four randomized placebo-controlled trials to determine if treatment-induced changes in hemodynamic values at 12 weeks accounted for the relationship between treatment assignment and the probability of early clinical events (death, lung transplantation, atrial septostomy, PAH hospitalization, withdrawal for clinical worsening, escalation in PAH therapy). We included 1119 subjects with PAH. The median (interquartile range) age was 48 (37 – 59), and 23% were men. 656 (59%) received active therapy (101 [15%] iloprost, 118 [18%] sitaxsentan, 204 [31%] sildenafil, and 233 [36%] subcutaneous treprostinil). Active treatment significantly lowered right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), and pulmonary vascular resistance and increased cardiac output and index (p < 0.01 for all). Changes in hemodynamic values (except for RAP and mPAP) were significantly associated with the risk of a clinical event (p ≤ 0.01 for all). While active treatment approximately halved the odds of a clinical event compared to placebo (p < 0.001), changes in hemodynamics accounted for only 1.2 – 13.9% of the overall treatment effect. Conclusions Treatment-induced changes in hemodynamics at 12 weeks only partially explain the impact of therapy on the probability of early clinical events in PAH. These findings suggest that resting hemodynamics are not valid surrogate endpoints for short-term events in PAH clinical trials. PMID:24951771

  13. Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation.

    PubMed

    Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Deng, Wei; Xu, Dachun; Han, Hui; Wang, Hao; Chen, Yuguo; Li, Yu; Wu, Dawei

    2014-07-18

    Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular+septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and attenuate pulmonary vascular remodeling after MCT induction. These beneficial effects were at least through the inhibition of PDGF-Rβ phosphorylation and its downstream signaling pathways. Therefore, IRN might be a potential candidate for the treatment of PAH. PMID:24950404

  14. Effects of Different Pulmonary Vasodilators on Arterial Saturation in a Model of Pulmonary Hypertension

    PubMed Central

    Becker, Eva Maria; Stasch, Johannes-Peter; Bechem, Martin; Keldenich, Jörg; Klipp, Alexandra; Schaefer, Katja; Ulbrich, Hannes-Friedrich; Truebel, Hubert

    2013-01-01

    Background Approved therapies for pulmonary arterial hypertension can induce oxygen desaturation when administered to patients with secondary forms of pulmonary hypertension (PH), probably due to an increase in ventilation/perfusion mismatch. Thus, so far these treatments have largely failed in secondary forms of PH. Methods We established an animal model of heterogeneous lung ventilation to evaluate the desaturation potential of mechanistically distinct vasoactive drugs launched or currently in clinical development for the treatment of PH. Single-lung ventilation was induced in five groups (N = 6) of anesthetized minipigs (7 weeks, 4 to 5 kg BW), and their hemodynamic parameters were monitored before and after intravenous injection of control (vehicle only), endothelin antagonist (bosentan; 0.3, 1, 3, 10 mg/kg), phosphodiesterase type 5 inhibitor (sildenafil; 3, 10, 30, 100 µg/kg), and soluble guanylate cyclase stimulators (BAY 41–8543 and riociguat; 1, 3, 10, 30 µg/kg). Cumulative doses were administered before successive unilateral ventilation cycles. The doses were chosen to achieve equal effect on blood pressure by the different pharmacologic principles. Results Single-lung ventilation resulted in transient increases in mean pulmonary artery pressure (mPAP) and desaturation. In contrast to control, all drugs dose-dependently decreased hypoxic mPAP (a positive treatment effect) and increased area under the arterial hemoglobin saturation curve (unwanted desaturation effect). Riociguat and bosentan reduced hypoxic mPAP to the greatest extent, while the soluble guanylate cyclase stimulators riociguat and BAY 41–8543 lowered arterial oxygen saturation of hemoglobin the least. Conclusions Future investigations will be required to confirm these findings in clinical settings. PMID:24015306

  15. Digital capillaroscopy as important tool for early diagnostics of arterial hypertension

    NASA Astrophysics Data System (ADS)

    Gurfinkel, Yu. I.; Sasonko, M. L.; Priezzhev, A. V.

    2015-03-01

    The study is aimed to determine the digital capillaroscopy possibilities in early diagnostics of an arterial hypertension. A total of 123 adult persons were examined in the study. The first group consisted of 40 patients with prehypertension (BP 130-139/85-89 mm Hg). The second group included 36 patients with 1-2 stage of hypertension (mean systolic BP 152.7±12 mm Hg). Patients in both groups did not receive regular drug therapy. The group of volunteers (n=47) included healthy adults without signs of cardiovascular pathology. The capillary circulation was examined on the nailbed using the optical digital capillaroscope developed by the company "AET", Russia. Diameters of the arterial and venous segments, perivascular zone size, capillary blood velocity, the degree of arterial loops narrowing and the density of the capillary network were estimated. In patients with arterial hypertension and even in patients with prehypertension remodeling and rarefaction of capillaries and the expressed narrowing their arterial loops were manifested. The results of the study revealed the presence of abnormalities of microcirculation parameters in patients of both groups. The capillaries density in both groups of patients was significantly lower than in healthy persons. The significant narrowing of arterial loops was revealed in patients with both arterial hypertension and prehypertension, in comparison with healthy volunteers. Capillary blood velocity did not differ significantly between healthy volunteers group and the group of prehypertensive patients. However in patients with hypertension this parameter was significantly lower in comparison with control group.

  16. Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults

    PubMed Central

    Taichman, Darren B.; Chung, Lorinda; Klinger, James R.; Lewis, Sandra; Mandel, Jess; Palevsky, Harold I.; Rich, Stuart; Sood, Namita; Rosenzweig, Erika B.; Trow, Terence K.; Yung, Rex; Elliott, C. Gregory; Badesch, David B.

    2014-01-01

    OBJECTIVE: Choices of pharmacologic therapies for pulmonary arterial hypertension (PAH) are ideally guided by high-level evidence. The objective of this guideline is to provide clinicians advice regarding pharmacologic therapy for adult patients with PAH as informed by available evidence. METHODS: This guideline was based on systematic reviews of English language evidence published between 1990 and November 2013, identified using the MEDLINE and Cochrane Library databases. The strength of available evidence was graded using the Grades of Recommendations, Assessment, Development, and Evaluation methodology. Guideline recommendations, or consensus statements when available evidence was insufficient to support recommendations, were developed using a modified Delphi technique to achieve consensus. RESULTS: Available evidence is limited in its ability to support high-level recommendations. Therefore, we drafted consensus statements to address many clinical questions regarding pharmacotherapy for patients with PAH. A total of 79 recommendations or consensus statements were adopted and graded. CONCLUSIONS: Clinical decisions regarding pharmacotherapy for PAH should be guided by high-level recommendations when sufficient evidence is available. Absent higher level evidence, consensus statements based upon available information must be used. Further studies are needed to address the gaps in available knowledge regarding optimal pharmacotherapy for PAH. PMID:24937180

  17. Dynamic respiratory mechanics and exertional dyspnoea in pulmonary arterial hypertension.

    PubMed

    Laveneziana, Pierantonio; Garcia, Gilles; Joureau, Barbara; Nicolas-Jilwan, Fadia; Brahimi, Toufik; Laviolette, Louis; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc; Similowski, Thomas

    2013-03-01

    Patients with pulmonary arterial hypertension (PAH) may exhibit reduced expiratory flows at low lung volumes, which could promote exercise-induced dynamic hyperinflation (DH). This study aimed to examine the impact of a potential exercise-related DH on the intensity of dyspnoea in patients with PAH undergoing symptom-limited incremental cardiopulmonary cycle exercise testing (CPET). 25 young (aged mean±sd 38±12 yrs) nonsmoking PAH patients with no evidence of spirometric obstruction and 10 age-matched nonsmoking healthy subjects performed CPET to the limit of tolerance. Ventilatory pattern, operating lung volumes (derived from inspiratory capacity (IC) measurements) and dyspnoea intensity (Borg scale) were assessed throughout CPET. IC decreased (i.e. DH) progressively throughout CPET in PAH patients (average 0.15 L), whereas it increased in all the healthy subjects (0.45 L). Among PAH patients, 15 (60%) exhibited a decrease in IC throughout exercise (average 0.50 L), whereas in the remaining 10 (40%) patients IC increased (average 0.36 L). Dyspnoea intensity and ventilation were greater in PAH patients than in controls at any stage of CPET, whereas inspiratory reserve volume was lower. We conclude that DH-induced mechanical constraints and excessive ventilatory demand occurred in these young nonsmoking PAH patients with no spirometric obstruction and was associated with exertional dyspnoea. PMID:22790921

  18. The Characteristics of Treated Pulmonary Arterial Hypertension Patients in Ontario.

    PubMed

    Vaid, Haris M; Camacho, Ximena; Granton, John T; Mamdani, Muhammad M; Yao, Zhan; Singh, Samantha; Juurlink, David N; Gomes, Tara

    2016-01-01

    Background. There are no Canadian prevalence studies on pulmonary arterial hypertension (PAH) to date. We described the characteristics of treated PAH patients and the healthcare utilization and costs associated with PAH in a population of public drug plan beneficiaries in Ontario, Canada. Methods. A retrospective cross-sectional analysis was conducted between April 2010 and March 2011 to identify treated PAH patients using population-based health administrative databases. We investigated demographic and clinical characteristics of treated PAH patients and conducted a cohort study to determine treatment patterns, healthcare utilization, and associated costs, over a one-year follow-up period (March 2012). Results. We identified 326 treated PAH cases in Ontario's publicly funded drug plan. Overall mean age was 59.4 years (±20.3 years) and over 77% of cases were women (n = 251). Combination therapy was used to treat 22.9% (n = 69) of cases, costing an average of $4,569 (SD $1,544) per month. Median monthly healthcare costs were $264 (IQR $96-$747) for those who survived and $2,021 (IQR $993-$6,399) for those who died over a one-year period, respectively (p < 0.01). Conclusions. PAH care in Ontario is complex and has high healthcare costs. This data may help guide towards improved patient management. PMID:27445555

  19. The Characteristics of Treated Pulmonary Arterial Hypertension Patients in Ontario

    PubMed Central

    Vaid, Haris M.; Camacho, Ximena; Granton, John T.; Mamdani, Muhammad M.; Yao, Zhan; Singh, Samantha; Juurlink, David N.; Gomes, Tara

    2016-01-01

    Background. There are no Canadian prevalence studies on pulmonary arterial hypertension (PAH) to date. We described the characteristics of treated PAH patients and the healthcare utilization and costs associated with PAH in a population of public drug plan beneficiaries in Ontario, Canada. Methods. A retrospective cross-sectional analysis was conducted between April 2010 and March 2011 to identify treated PAH patients using population-based health administrative databases. We investigated demographic and clinical characteristics of treated PAH patients and conducted a cohort study to determine treatment patterns, healthcare utilization, and associated costs, over a one-year follow-up period (March 2012). Results. We identified 326 treated PAH cases in Ontario's publicly funded drug plan. Overall mean age was 59.4 years (±20.3 years) and over 77% of cases were women (n = 251). Combination therapy was used to treat 22.9% (n = 69) of cases, costing an average of $4,569 (SD $1,544) per month. Median monthly healthcare costs were $264 (IQR $96–$747) for those who survived and $2,021 (IQR $993–$6,399) for those who died over a one-year period, respectively (p < 0.01). Conclusions. PAH care in Ontario is complex and has high healthcare costs. This data may help guide towards improved patient management. PMID:27445555

  20. Redox biology in pulmonary arterial hypertension (2013 Grover Conference Series).

    PubMed

    Fessel, Joshua P; West, James D

    2015-12-01

    Through detailed interrogation of the molecular pathways that contribute to the development of pulmonary arterial hypertension (PAH), the separate but related processes of oxidative stress and cellular metabolic dysfunction have emerged as being critical pathogenic mechanisms that are as yet relatively untargeted therapeutically. In this review, we have attempted to summarize some of the important existing studies, to point out areas of overlap between oxidative stress and metabolic dysfunction, and to do so under the unifying heading of redox biology. We discuss the importance of precision in assessing oxidant signaling versus oxidant injury and why this distinction matters. We endeavor to advance the discussion of carbon-substrate metabolism beyond a focus on glucose and its fate in the cell to encompass other carbon substrates and some of the murkiness surrounding our understanding of how they are handled in different cell types. Finally, we try to bring these ideas together at the level of the mitochondrion and to point out some additional points of possible cognitive dissonance that warrant further experimental probing. The body of beautiful science regarding the molecular and cellular details of redox biology in PAH points to a future that includes clinically useful therapies that target these pathways. To fully realize the potential of these future interventions, we hope that some of the issues raised in this review can be addressed proactively. PMID:26697167

  1. Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension

    PubMed Central

    Johnson, Jennifer A.; Hemnes, Anna R.; Perrien, Daniel S.; Schuster, Manfred; Robinson, Linda J.; Gladson, Santhi; Loibner, Hans; Bai, Susan; Blackwell, Tom R.; Tada, Yuji; Harral, Julie W.; Talati, Megha; Lane, Kirk B.; Fagan, Karen A.

    2012-01-01

    The heritable form of pulmonary arterial hypertension (PAH) is typically caused by a mutation in bone morphogenic protein receptor type 2 (BMPR2), and mice expressing Bmpr2 mutations develop PAH with features similar to human disease. BMPR2 is known to interact with the cytoskeleton, and human array studies in PAH patients confirm alterations in cytoskeletal pathways. The goal of this study was to evaluate cytoskeletal defects in BMPR2-associated PAH. Expression arrays on our Bmpr2 mutant mouse lungs revealed cytoskeletal defects as a prominent molecular consequence of universal expression of a Bmpr2 mutation (Rosa26-Bmpr2R899X). Pulmonary microvascular endothelial cells cultured from these mice have histological and functional cytoskeletal defects. Stable transfection of different BMPR2 mutations into pulmonary microvascular endothelial cells revealed that cytoskeletal defects are common to multiple BMPR2 mutations and are associated with activation of the Rho GTPase, Rac1. Rac1 defects are corrected in cell culture and in vivo through administration of exogenous recombinant human angiotensin-converting enzyme 2 (rhACE2). rhACE2 reverses 77% of gene expression changes in Rosa26-Bmpr2R899X transgenic mice, in particular, correcting defects in cytoskeletal function. Administration of rhACE2 to Rosa26-Bmpr2R899X mice with established PAH normalizes pulmonary pressures. Together, these findings suggest that cytoskeletal function is central to the development of BMPR2-associated PAH and that intervention against cytoskeletal defects may reverse established disease. PMID:22180660

  2. Redox biology in pulmonary arterial hypertension (2013 Grover Conference Series)

    PubMed Central

    2015-01-01

    Abstract Through detailed interrogation of the molecular pathways that contribute to the development of pulmonary arterial hypertension (PAH), the separate but related processes of oxidative stress and cellular metabolic dysfunction have emerged as being critical pathogenic mechanisms that are as yet relatively untargeted therapeutically. In this review, we have attempted to summarize some of the important existing studies, to point out areas of overlap between oxidative stress and metabolic dysfunction, and to do so under the unifying heading of redox biology. We discuss the importance of precision in assessing oxidant signaling versus oxidant injury and why this distinction matters. We endeavor to advance the discussion of carbon-substrate metabolism beyond a focus on glucose and its fate in the cell to encompass other carbon substrates and some of the murkiness surrounding our understanding of how they are handled in different cell types. Finally, we try to bring these ideas together at the level of the mitochondrion and to point out some additional points of possible cognitive dissonance that warrant further experimental probing. The body of beautiful science regarding the molecular and cellular details of redox biology in PAH points to a future that includes clinically useful therapies that target these pathways. To fully realize the potential of these future interventions, we hope that some of the issues raised in this review can be addressed proactively. PMID:26697167

  3. The molecular targets of approved treatments for pulmonary arterial hypertension

    PubMed Central

    Humbert, Marc; Ghofrani, Hossein-Ardeschir

    2016-01-01

    Until recently, three classes of medical therapy were available for the treatment of pulmonary arterial hypertension (PAH)—prostanoids, endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors. With the approval of the soluble guanylate cyclase stimulator riociguat, an additional drug class has become available targeting a distinct molecular target in the same pathway as PDE5 inhibitors. Treatment recommendations currently include the use of all four drug classes to treat PAH, but there is a lack of comparative data for these therapies. Therefore, an understanding of the mechanistic differences between these agents is critical when making treatment decisions. Combination therapy is often used to treat PAH and it is therefore important that physicians understand how the modes of action of these drugs may interact to work as complementary partners, or potentially with unwanted consequences. Furthermore, different patient phenotypes mean that patients respond differently to treatment; while a certain monotherapy may be adequate for some patients, for others it will be important to consider alternating or combining compounds with different molecular targets. This review describes how the four currently approved drug classes target the complex pathobiology of PAH and will consider the distinct target molecules of each drug class, their modes of action, and review the pivotal clinical trial data supporting their use. It will also discuss the rationale for combining drugs (or not) from the different classes, and review the clinical data from studies on combination therapy. PMID:26219978

  4. [Pulmonary arterial hypertension: a voyage around the year 2008].

    PubMed

    Baloira, Adolfo

    2009-01-01

    There have been spectacular developments in pulmonary arterial hypertension (PAH), both in its treatment and knowledge of its pathogenesis. Several studies have been published throughout 2008 that have contributed to improve these two aspects a little. As regards the pathogenesis, mutations in BMPR2 continue gaining points as fundamental factors in the development of the disease. It has been shown that patients who carry any of them have a more rapid and severe clinical course. There is a relationship between the BMPR2 pathway and inflammation of the pulmonary vascular tree. A new anti-endothelin drug, ambrisentan, has also appeared on the scene this year. With an efficacy comparable to other drugs of its group, the secondary effects appear to be a lot less. An important work has been the demonstration of an improvement in several parameters in functional class II in patients with PAH with bosentan. Results using new combinations, such as sildenafil and epoprostenol, have also been presented. A common type of PAH is that which seems to be associated with thromboembolic disease. Treatment with sildenafil and in some selected cases, percutaneous angioplasty, has obtained favourable responses. Finally, in 2008, two new consensus documents have emerged, one Spanish and the other British, which in the light of current knowledge, give a clearer insight into the management of this serious disease. PMID:19303531

  5. A review of pulmonary arterial hypertension: role of ambrisentan.

    PubMed

    Barst, Robyn J

    2007-01-01

    Pulmonary arterial hypertension (PAH) is a rare fatal disease. Current disease-specific therapeutic interventions in PAH target 1 of 3 established pathways in disease pathobiology: prostacyclin, nitric oxide, and endothelin-1. Endothelin receptor antagonists (ERAs) act on the endothelin pathway by blocking binding of endothelin-1 to its receptors (endothelin type-A [ET(A)] and/or type-B [ET(B)]) on the surface of endothelial and smooth muscle cells. Ambrisentan is an oral, once-daily, ET(A)-selective ERA in development for the treatment of PAH. In Phase 3 clinical trials in patients with PAH, ambrisentan (2.5-10 mg orally once-daily) improved exercise capacity, Borg dyspnea index, time to clinical worsening, WHO functional class, and quality of life compared with placebo. Ambrisentan provided durable (at least 2 years) improvement in exercise capacity in a Phase 2 long-term extension study. Ambrisentan was well tolerated with a lower incidence and severity of liver function test abnormalities compared with the ET(A)/ET(B) ERA, bosentan, and the ET(A)-selective ERA, sitaxsentan. Ambrisentan does not induce or inhibit P450 enzymes; therefore, ambrisentan is unlikely to affect the pharmacokinetics of P450-metabolized drugs. The demonstration of clinical efficacy, low incidence of acute hepatic toxicity, and low risk of drug-drug interactions support the role of ambrisentan for the treatment of PAH. PMID:17583171

  6. Connective tissue disease-associated pulmonary arterial hypertension

    PubMed Central

    Howard, Luke S.

    2015-01-01

    Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

  7. Pharmacoeconomic evidence of bosentan for pulmonary arterial hypertension.

    PubMed

    Strange, Geoff; Keogh, Anne; Dalton, Brad; Gabbay, Eli

    2011-06-01

    In this article, we review randomized controlled trials, open-label trials and pharmacoeconomic models of bosentan for the management of patients with pulmonary arterial hypertension. Bosentan consistently improves WHO functional class and quality of life, slows clinical worsening and is associated with improved survival compared with historical treatment. Although head-to-head trials are scarce, data directly comparing bosentan with sildenafil indicate no clinically significant differences between treatments as measured by the 6-min walk distance alone. Compared with historical care, bosentan treatment, over a 15-30-year period, increases the number of quality-adjusted life years (3.49 years). Economic modeling suggests that the cost-effectiveness of bosentan is similar to that of ambrisentan (US$43,725-57,778 per quality-adjusted life year), not as cost effective as sildenafil (at 20 mg three-times daily) and more cost effective than iloprost. More randomized controlled trials of longer duration are required to confirm the results from these economic models. PMID:21671693

  8. Initial dual oral combination therapy in pulmonary arterial hypertension.

    PubMed

    Sitbon, Olivier; Sattler, Caroline; Bertoletti, Laurent; Savale, Laurent; Cottin, Vincent; Jaïs, Xavier; De Groote, Pascal; Chaouat, Ari; Chabannes, Céline; Bergot, Emmanuel; Bouvaist, Hélène; Dauphin, Claire; Bourdin, Arnaud; Bauer, Fabrice; Montani, David; Humbert, Marc; Simonneau, Gérald

    2016-06-01

    Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met.This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III-IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8).All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively.Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment. PMID:26989105

  9. [Phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension].

    PubMed

    Beltrán-Gámez, Miguel E; Sandoval-Zárate, Julio; Pulido, Tomás

    2015-01-01

    In experimental and clinical cardiology, phosphodiesterase type 5 (PDE-5) inhibitors have brought scientific interest as a therapeutic tool in pulmonary arterial hypertension (PAH) management in recent years. Phosphodiesterases are a superfamily of enzymes that inactivate cyclic adenosine monophosphate and cyclic guanosine monophosphate, the second messengers of prostacyclin and nitric oxide. The rationale for the use of PDE-5 inhibitors in PAH is based on their capacity to overexpresss the nitric oxide pathway pursued inhibition of cyclic guanosine monophosphate hydrolysis. By increasing cyclic guanosine monophosphate levels it promotes vasodilation, antiproliferative and pro-apoptotic effects that may reverse pulmonary vascular remodeling. There is also evidence that these drugs may directly enhance right ventricular contractility through an increase in cyclic adenosine monophosphate mediated by the inhibition of the cyclic guanosine monophosphate -sensitive PDE-3. Sildenafil, tadalafil and vardenafil are 3 specific PDE-5 inhibitors in current clinical use, which share similar mechanisms of action but present some significant differences regarding potency, selectivity for PDE-5 and pharmacokinetic properties. Sildenafil received approval in 2005 by the Food and Drug Administration and the European Medicines Agency and tadalafil in 2009 by the Food and Drug Administration and the European Medicines Agency for the treatment of PAH in patients classified as NYHA/WHO functional class II and III. In Mexico, sildenafil and tadalafil were approved by Comisión Federal de Protección contra Riesgos Sanitarios for this indication in 2010 and 2011, respectively. PMID:26047999

  10. The Rapid Initiation, Titration, and Transition from Intravenous to Oral Treprostinil in a Patient with Severe Pulmonary Arterial Hypertension

    PubMed Central

    Gleason, James Benjamin; Dolan, Justin; Piran, Pirouz; Rahaghi, Franck Farzad

    2015-01-01

    In patients who require urgent initiation of pulmonary arterial hypertension medications due to disease progression, it is customary to start intravenous prostacyclin therapy, typically during a hospital admission. If there are complicating factors or relative contraindications to intravenous and subcutaneous prostanoids, oral treprostinil provides another pathway to prostanoid therapy, but this usually requires a prolonged titration. We describe the case of a thirty-six-year-old male with severe pulmonary arterial hypertension and contraindication to intravenous and subcutaneous prostanoid therapy due to congenital deafness and the risk of not hearing the intravenous pump alarms. Intravenous treprostinil was initiated, titrated to high dose, and then rapidly transitioned to oral treprostinil. A rapid initiation, titration, and transition from intravenous to oral treprostinil can be safely performed under watchful supervision in order to achieve higher and more efficacious doses of oral treprostinil in a timely manner. PMID:26457220

  11. Serum levels of soluble ICAM-1 in children with pulmonary artery hypertension.

    PubMed

    Oguz, Melahat Melek; Oguz, Ayse Deniz; Sanli, Cihat; Cevik, Ayhan

    2014-04-01

    This prospective cross-sectional study attempted to determine both the usefulness of the serum intercellular adhesion molecule-1 (ICAM-1) as a biomarker for pulmonary artery hypertension secondary to congenital heart disease and the nature of this marker's association with catheter angiographic findings. Our study included a total of 70 male and female children, comprising 30 patients with both pulmonary artery hypertension and congenital heart disease, 20 patients with congenital heart disease alone, and 20 healthy control subjects. Levels of ICAM-1 in plasma samples from all groups were measured by the enzyme-linked immunosorbent assay method. Cardiac catheterization was also performed in all patients. The mean serum ICAM-1 levels in pediatric patients who had congenital heart disease with and without pulmonary artery hypertension were 349.6 ± 72.9 ng/mL and 312.3 ± 69.5 ng/mL, respectively (P=0.002). In healthy control subjects, the mean serum ICAM-1 level was 231.4 ± 60.4 ng/mL. According to the results of this study, the ICAM-1 level of the pulmonary artery hypertension group was significantly higher than those of the congenital heart disease group and the healthy control group. Correlation analysis showed that ICAM-1 level was correlated with systolic and mean pulmonary artery pressures (r=0.62, P=0.001; r=0.57, P=0.001)-which are 2 important values used in diagnosis of pulmonary artery hypertension. Moreover, receiver operating characteristic analysis yielded consistent results for the prediction of pulmonary artery hypertension. Therefore, we conclude that ICAM-1 has potential use as a biomarker for the diagnosis and follow-up of pulmonary artery hypertension. PMID:24808775

  12. Serum Levels of Soluble ICAM-1 in Children with Pulmonary Artery Hypertension

    PubMed Central

    Oguz, Melahat Melek; Oguz, Ayse Deniz; Sanli, Cihat; Cevik, Ayhan

    2014-01-01

    This prospective cross-sectional study attempted to determine both the usefulness of the serum intercellular adhesion molecule-1 (ICAM-1) as a biomarker for pulmonary artery hypertension secondary to congenital heart disease and the nature of this marker's association with catheter angiographic findings. Our study included a total of 70 male and female children, comprising 30 patients with both pulmonary artery hypertension and congenital heart disease, 20 patients with congenital heart disease alone, and 20 healthy control subjects. Levels of ICAM-1 in plasma samples from all groups were measured by the enzyme-linked immunosorbent assay method. Cardiac catheterization was also performed in all patients. The mean serum ICAM-1 levels in pediatric patients who had congenital heart disease with and without pulmonary artery hypertension were 349.6 ± 72.9 ng/mL and 312.3 ± 69.5 ng/mL, respectively (P=0.002). In healthy control subjects, the mean serum ICAM-1 level was 231.4 ± 60.4 ng/mL. According to the results of this study, the ICAM-1 level of the pulmonary artery hypertension group was significantly higher than those of the congenital heart disease group and the healthy control group. Correlation analysis showed that ICAM-1 level was correlated with systolic and mean pulmonary artery pressures (r=0.62, P=0.001; r=0.57, P=0.001)—which are 2 important values used in diagnosis of pulmonary artery hypertension. Moreover, receiver operating characteristic analysis yielded consistent results for the prediction of pulmonary artery hypertension. Therefore, we conclude that ICAM-1 has potential use as a biomarker for the diagnosis and follow-up of pulmonary artery hypertension. PMID:24808775

  13. Neonatal pulmonary artery thrombosis presenting as persistent pulmonary hypertension of the newborn.

    PubMed

    Sawyer, Taylor; Antle, Amanda; Studer, Matthew; Thompson, Mark; Perry, Stanton; Mahnke, C Becket

    2009-05-01

    Pulmonary artery thrombosis in neonates occurs rarely. This report describes the case of a term infant with a pulmonary artery thrombosis presenting as persistent pulmonary hypertension of the newborn. The risk factors identified in the case included maternal diabetes and heterozygous factor V Leiden deficiency. The pulmonary thrombus was successfully treated with percutaneous catheter-based embolectomy. PMID:19052800

  14. MR and CT imaging of the structural and functional changes of pulmonary arterial hypertension

    PubMed Central

    Schiebler, Mark L.; Bhalla, Sanjeev; Runo, James; Jarjour, Nizar; Roldan, Alejandro; Chesler, Naomi; François, Christopher J.

    2013-01-01

    The current Dana Point classification system (2009) divides elevation of pulmonary artery pressure into Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension (PH). Fortunately, pulmonary arterial hypertension (PAH) is not a common disease. However, with the aging of the first world’s population, heart failure is now an important cause of pulmonary hypertension with up to 9% of the population involved. PAH is usually asymptomatic until late in the disease process. While there are indirect features of PAH found on noninvasive imaging studies, the diagnosis and management still requires right heart catheterization. Imaging features of PAH include: 1. Enlargement of the pulmonary trunk and main pulmonary arteries, 2. Decreased pulmonary arterial compliance, 3. Tapering of the peripheral pulmonary arteries, 4. Enlargement of the inferior vena cava, and 5. Increased mean transit time. The chronic requirement to generate high pulmonary arterial pressures measurably affects the right heart and main pulmonary artery. This change in physiology causes the following structural and functional alterations that have been shown to have prognostic significance: Relative area change of the pulmonary trunk, RVSVindex, RVSV, RVEDVindex, LVEDVindex, and baseline RVEF <35%. All of these variables can be quantified non-invasively and followed longitudinally in each patient using MRI to modify the treatment regimen. Untreated PAH frequently results in a rapid clinical decline and death within 3 years of diagnosis. Unfortunately, even with treatment, less than 1/2 of these patients are alive at four years. PMID:23612440

  15. Update on the clinical utility of sildenafil in the treatment of pulmonary arterial hypertension

    PubMed Central

    Ramani, Gautam V; Park, Myung H

    2010-01-01

    Sildenafil is an orally administered phosphodiesterase type 5 inhibitor that is approved for the treatment of pulmonary arterial hypertension (PAH). The hemodynamic effects of sildenafil are mitigated primarily via potentiating the effects of endogenous nitric oxide, leading to smooth muscle cell relaxation and reductions in pulmonary arterial pressures and pulmonary vascular resistance. When added to standard background therapy in patients with idiopathic or associated PAH from congenital heart disease, anorexigen use, or connective tissue disease, sildenafil treatment results in improved exercise capacity as measured by 6 minute walk distance, improved hemodynamics, and favorable changes in quality of life. Sildenafil use is contraindicated with concomitant nitrate administration, and caution should be exercised when used in combination with antihypertensive agents due to risks of precipitating hypotension. Side effects are generally mild, and include flushing, headaches, and epistaxis. The combination of sildenafil with intravenous epoprostenol is safe and well tolerated, and further improves exercise capacity. Sildenafil is approved only for treatment of PAH, and although emerging data suggest a potential role in treating other types of pulmonary hypertension, larger trials are required to confirm these findings. PMID:20531962

  16. Failure and Success of Percutaneous Angioplasty in a Hypertensive Child with Bilateral Renal Artery Stenosis

    SciTech Connect

    Giavroglou, Constantinos; Tsifountoudis, Ioannis; Boutzetis, Theodoros; Kiskinis, Dimitrios

    2009-01-15

    We describe the clinical course of a 5-year-old girl with severe arterial hypertension that was uncontrollable with antihypertensive medication. Renal angiography revealed bilateral renal artery stenoses. Because percutaneous transluminal renal angioplasty (PTRA) failed to dilate the stenotic lesions, a renal artery bypass grafting in both renal arteries was performed. The patient remained normotensive for 7 months, and after that the arterial pressure increased again. Digital subtraction angiography demonstrated stenosis at the peripheral and central anastomosis of the vein graft that was used for revascularization of the left kidney. PTRA was decided on and successful patency was achieved. The patient has now been normotensive for a period of 5 years.

  17. Arterial Hypertension and other risk factors associated with cardiovascular diseases among adults1

    PubMed Central

    Radovanovic, Cremilde Aparecida Trindade; dos Santos, Lucimary Afonso; Carvalho, Maria Dalva de Barros; Marcon, Sonia Silva

    2014-01-01

    OBJECTIVE: to identify the prevalence of arterial hypertension and its association with cardiovascular risk factors among adults. METHOD: cross-sectional, population-based, descriptive study conducted with 408 adult individuals. Data were collected through a questionnaire and measurements of weight, height and waist circumference. Person's Chi-square and multiple logistic regression were used in the data analysis. RESULTS: 23.03% of the individuals reported hypertension with a higher prevalence among women. Odds Ratio indicated that smoking, body mass index, waist circumference, diabetes mellitus and dyslipidemia were positively associated with arterial hypertension. CONCLUSION: high self-reported hypertension and its association with other cardiovascular risk factors such as diabetes, obesity and dyslipidemia show the need for specific nursing interventions and the implementation of protocols focused on minimizing complications arising from hypertension, as well as to prevent the emergence of other cardiovascular diseases. PMID:25296137

  18. Pulmonary Arterial Stiffness: Toward a New Paradigm in Pulmonary Arterial Hypertension Pathophysiology and Assessment.

    PubMed

    Schäfer, Michal; Myers, Cynthia; Brown, R Dale; Frid, Maria G; Tan, Wei; Hunter, Kendall; Stenmark, Kurt R

    2016-01-01

    Stiffening of the pulmonary arterial bed with the subsequent increased load on the right ventricle is a paramount feature of pulmonary hypertension (PH). The pathophysiology of vascular stiffening is a complex and self-reinforcing function of extracellular matrix remodeling, driven by recruitment of circulating inflammatory cells and their interactions with resident vascular cells, and mechanotransduction of altered hemodynamic forces throughout the ventricular-vascular axis. New approaches to understanding the cell and molecular determinants of the pathophysiology combine novel biopolymer substrates, controlled flow conditions, and defined cell types to recapitulate the biomechanical environment in vitro. Simultaneously, advances are occurring to assess novel parameters of stiffness in vivo. In this comprehensive state-of-art review, we describe clinical hemodynamic markers, together with the newest translational echocardiographic and cardiac magnetic resonance imaging methods, to assess vascular stiffness and ventricular-vascular coupling. Finally, fluid-tissue interactions appear to offer a novel route of investigating the mechanotransduction processes and disease progression. PMID:26733189

  19. [Anesthetic Management for Non-cardiac Surgery in a Patient with Severe Pulmonary Arterial Hypertension].

    PubMed

    Ohno, Sho; Niiyama, Yukitoshi; Murouchi, Takeshi; Yamakage, Michiaki

    2016-05-01

    Severe pulmonary arterial hypertension is a significant risk factor for anesthetic management in patients undergoing even non-cardiac surgery. A 64-year-old female patient with severe pulmonary arterial hypertension was scheduled to undergo inguinal hernioplasty. Preoperative systolic pulmonary arterial pressure was 115 mmHg. We selected monitored anesthesia care with 0.2-0.5 μg x kg(-1) x hr(-1) dexmedetomidine and ultrasound-guided iliohypogastric block. Thereafter, LiDCOrapid was used to acquire the hemodynamic responses during surgery. Continuous iliohypogastric block produced postoperative pain relief and the supplemental analgesic was not needed. The monitored anesthesia care by dexmedetomidine and ultrasound guided continuous iliohypogastric block would be a safe procedure for patients with severe pulmonary arterial hypertension undergoing non-cardiac surgery. LiDCO rapid could be low invasive and useful as a hemodaynamic monitor in such a case. PMID:27319099

  20. [The role of the team of family physician in prevention of changing risk factors important in development of arterial hypertension].

    PubMed

    Beganlić, Azijada; Batić-Mujanović, Olivera; Tulumović, Ajsa; Zilzić, Muharem

    2005-01-01

    Arterial hypertension (AH) is one of the commonest noninfective chronic disease according to its important and the role in the morbidity and mortality, which is the reason for patients coming to the family phisician. Detection and treatment of high blood pressure are the major responsibility of physician in the primary care. If the family physician team (physician and nurse) make a good assessment of the risk factors which is important in development of arterial hypertension, the appearance of disease and its complications can be prevented or delayed. The most important for prevention of arterial hypertension is adoption a healthy lifestyle and it is nonseparate part of arterial hypertension treatment. PMID:16268072

  1. Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation

    SciTech Connect

    Guo, Haipeng; Zhang, Xin; Cui, Yuqian; Deng, Wei; Xu, Dachun; Han, Hui; Wang, Hao; Chen, Yuguo; Li, Yu; Wu, Dawei

    2014-07-18

    Highlights: • We focus on PASMCs proliferation in the pathogenesis of PAH. • Isorhynchophylline inhibited PASMCs proliferation and alleviated PAH. • IRN blocked PDGF-Rβ phosphorylation and its downstream signal transduction. • IRN regulated cyclins and CDKs to arrest cell cycle in the G0/G1 phase. • We reported IRN has the potential to be a candidate for PAH treatment. - Abstract: Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular + septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rβ, ERK1/2, Akt/GSK3β, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and

  2. Improved survival in limited scleroderma-related pulmonary artery hypertension.

    PubMed

    Marini, Carlo; Formichi, Bruno; Bauleo, Carolina; Michelassi, Claudio; Pancani, Roberta; Prediletto, Renato; Miniati, Massimo; Catapano, Giosuè; Monti, Simonetta; Mannucci, Francesca; Tavoni, Antonio; D'Ascanio, Anna; Pastormerlo, Luigi Emilio; Giannoni, Alberto; Giuntini, Carlo

    2014-06-01

    Reportedly, patients with scleroderma-related pulmonary hypertension (SSc-PAH) respond poorly to new vasoactive drugs (NVD). Forty-nine SSc-PAH patients underwent right heart catheterization (RHC) and, according to NVD availability, divided as follows: Group 1 (n = 23, from 1999 to 2004, poor availability), and Group 2 (n = 26, from 2005 to 2010, good availability). Before diagnostic RHC, NVD had been given to 30 % of the patients in Group 1, and 58 % of those in Group 2 (p = 0.049). At diagnosis, patients in Group 1 had greater heart dilatation (p < 0.01), higher mean pulmonary artery pressure (p < 0.05), lower pulmonary artery capacitance (p < 0.05), and lower carbon monoxide lung diffusing capacity (DLco, p < 0.05) than those in Group 2. At a median follow-up time of 15.5 months, DLco further decreased in Group 1 (p < 0.05), whereas cardiac index increased in Group 2 (p < 0.05). At 36 months of follow-up, 72.4 % of the patients in Group 2 were still alive as opposed to 30.4 % in Group 1 (p = 0.02). In multivariate analysis, DLco and mixed venous oxygen saturation (SvO2) were independent predictors of survival. A value of DLco <7.2 mL/mmHg/min was associated with a hazard ratio (HR) of 5.3 (p < 0.001); for SvO2 <63.8 %, the HR was 3.7 (p < 0.01).NVD have beneficial effects in patients with SSc-PAH. Both DLco and SvO2 are predictors of survival and may assist in planning treatment. PMID:23361526

  3. Relationship between occupational exposure to lead and local arterial stiffness and left ventricular diastolic function in individuals with arterial hypertension

    SciTech Connect

    Poreba, Rafal; Gac, Pawel; Poreba, Malgorzata; Antonowicz-Juchniewicz, Jolanta; Andrzejak, Ryszard

    2011-08-01

    Relationship between occupational exposure to lead and frequency of complications in persons with arterial hypertension has been poorly investigated. This study aimed at evaluation of the relationship between occupational exposure to lead and manifestation of an increased local arterial stiffness and left ventricular diastolic dysfunction. The studies included 105 men (mean age: 44.47 {+-} 9.12 years) with arterial hypertension, treated with hypotensive drugs: group I - men occupationally exposed to lead (n = 53), and group II - men not exposed to lead (n = 52). In echocardiographic examination, the left ventricular diastolic dysfunction was diagnosed significantly more frequently in group I than in group II. In eTracking examination mean values of stiffness parameter ({beta}), augmentation index (AI) and one-point pulse wave velocity (PWV-{beta}) were significantly higher and mean values of arterial compliance (AC) were significantly lower in group I than in group II. The logistic regression showed that in the group of persons with arterial hypertension occupationally exposed to lead a more advanced age, higher blood lead concentration and higher mean values of augmentation index represent independent risk factors of left ventricular diastolic dysfunction. The multifactorial regression showed that amongst persons with arterial hypertension occupationally exposed to lead higher blood zinc protoporphyrin concentration, a more advanced age and higher value of body mass index (BMI) represent independent risk factors of an increased local arterial stiffness. In summary, we should note that in the group of persons with arterial hypertension occupationally exposed to lead the study has demonstrated a significantly more frequent manifestation of left ventricular diastolic dysfunction and an increase in local arterial stiffness. - Highlights: > Amongst persons with AH exposed to Pb higher ZnPP represent independent risk factor of increased local arterial stiffness

  4. [Chronopharmacokinetics of nadolol in patients with arterial hypertension].

    PubMed

    Rumiantsev, D O; Duda, S G; Poteshnykh, A V; Piotrovskiĭ, V K; Metelitsa, V I; Belolipetskaia, V G

    1997-01-01

    The pharmacokinetics of nadolol in blood serum and its excretion in the urine were studied in 6 male patients (aged from 35 to 59 years) with arterial hypertension for 48 h and, respectively, 72 h after a single per os administration of nadolol in a dose of 80 mg in the morning (9.00 a.m.), in daytime (15.00 p.m.) and in the evening (20.00 p.m.). The concentration of nadolol in the blood serum and urine was determined by high performance liquid chromatography with fluorescence detection. Analysis of the obtained data showed maximum blood serum nadolol concentration and the area under the concentration--time curve to be lower (93 ng/ml and 1786 ng h/ml) in the case of evening medication, and the peroral clearance and kinetic distribution volume to be higher (44.8 l/h and 940 l) than after morning medication (188 ng/ml, 2816 ng h/ml, and 28.4 l/h and 650 l, respectively). The corresponding parameters after daytime medication had intermediate values. The half-life period, mean retention time, and time of achievement of maximum blood serum nadolol concentration did not depend on the time of medication and were in the range of 15.2-15.8 h, 21.1-22.0 h, and 2.9-4.0 h, respectively. The pharmacokinetic parameters characterizing nadolol excretion with the urine were independent of the time of its intake. On the basis of the character of the detected circadian changes in the parameters of nadolol pharmacokinetics it is suggested that these changes reflect the circadian variations in the absorption of the drug in the gastrointestinal tract. PMID:9483406

  5. Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension

    PubMed Central

    Schroer, Alison K.; Chen, Peter; Ryzhova, Larisa M.; Gladson, Santhi; Shay, Sheila; Hutcheson, Joshua D.; Merryman, W. David

    2016-01-01

    Serotonergic anorexigens are the primary pharmacologic risk factor associated with pulmonary arterial hypertension (PAH), and the resulting PAH is clinically indistinguishable from the heritable form of disease, associated with BMPR2 mutations. Both BMPR2 mutation and agonists to the serotonin receptor HTR2B have been shown to cause activation of SRC tyrosine kinase; conversely, antagonists to HTR2B inhibit SRC trafficking and downstream function. To test the hypothesis that a HTR2B antagonist can prevent BMRP2 mutation induced PAH by restricting aberrant SRC trafficking and downstream activity, we exposed BMPR2 mutant mice, which spontaneously develop PAH, to a HTR2B antagonist, SB204741, to block the SRC activation caused by BMPR2 mutation. SB204741 prevented the development of PAH in BMPR2 mutant mice, reduced recruitment of inflammatory cells to their lungs, and reduced muscularization of their blood vessels. By atomic force microscopy, we determined that BMPR2 mutant mice normally had a doubling of vessel stiffness, which was substantially normalized by HTR2B inhibition. SB204741 reduced SRC phosphorylation and downstream activity in BMPR2 mutant mice. Gene expression arrays indicate that the primary changes were in cytoskeletal and muscle contractility genes. These results were confirmed by gel contraction assays showing that HTR2B inhibition nearly normalizes the 400% increase in gel contraction normally seen in BMPR2 mutant smooth muscle cells. Heritable PAH results from increased SRC activation, cellular contraction, and vascular resistance, but antagonism of HTR2B prevents SRC phosphorylation, downstream activity, and PAH in BMPR2 mutant mice. PMID:26863209

  6. Expert opinion on available options treating pulmonary arterial hypertension.

    PubMed

    Naeije, Robert; Huez, Sandrine

    2007-10-01

    Until in the early nineties, pulmonary arterial hypertension (PAH) was a uniformly fatal disease, with a median life expectancy of approximately 2.5 years. Uncontrolled studies showed that a small proportion of patients responded to high-dose calcium channel blockers, retrospective studies supported the use of anticoagulant therapy and heart-lung or lung transplantation remained the only option. In 1996, a 3-month randomised, placebo-controlled trial showed that chronic intravenous epoprostenol (synthetic prostacyclin) improved functional state, exercise capacity, haemodynamics, and even survival in patients with idiopathic PAH. Similar benefits were subsequently reported and extended to all PAH categories, and confirmed with more stable prostacyclin analogues administered subcutaneously (treprostinil), by inhalation (iloprost), or even orally (beraprost). In the early 2000s, two randomised controlled trials showed efficacy of the oral intake of the dual endothelin A/B receptor antagonist bosentan. Two selective endothelin-A receptor antagonists, sitaxsentan and ambrisentan, are being developed. Finally, a randomised controlled trial has established the therapeutic efficacy of phosphodiesterase-5 inhibition with sildenafil, introducing a third signalling pathway to be targeted by the pharmacological treatment of PAH. Another phosphodiesterase-5 inhibitor, tadalafil, is already being evaluated. While all these treatments have markedly improved the lives of PAH patients, they have not offered yet a cure of the disease. Multi-drug approaches are now under evaluation, with more ambitious therapeutic goals. Alternative approaches with stem cells, RhoA-Rho-kinase inhibitors, platelet derived growth factor inhibitors and vasoactive intestinal peptides are being considered. PMID:17927481

  7. Phase I safety study of ranolazine in pulmonary arterial hypertension

    PubMed Central

    Schilz, Robert; Mediratta, Anuj; Addetia, Karima; Coslet, Sandra; Thomeas, Vasiliki; Gillies, Hunter; Oudiz, Ronald J.

    2015-01-01

    Abstract Pulmonary arterial hypertension (PAH) causes right ventricular ischemia, dysfunction, and failure. PAH patients may benefit from antianginal agents based on a shared pathophysiology with left ventricular ischemia. A single-center, randomized, placebo-controlled trial (1∶1) to assess the acute vasoreactivity and safety of ranolazine in PAH was conducted. Plasma samples for pharmacokinetic (PK) studies were drawn during hemodynamic measurements at 0, 60, 90, 120, 240, and 360 minutes from a Swan-Ganz catheter. All patients received 500-mg doses, uptitrated to 1,000 mg at week 4, monthly evaluations, and a complete objective assessment after 12 weeks, followed by an open-label extension. Thirteen patients were randomized and 12 enrolled (6 ranolazine, 6 placebo). All patients completed the acute phase; 10 completed the 12-week study. There were no acute changes in invasive hemodynamics. At 12 weeks ranolazine was well tolerated. Only 1 of the 5 patients on ranolazine had a serum concentration considered to be in the therapeutic range. Two serious adverse events required early withdrawal (both in the ranolazine group); gastrointestinal complaints were the most common adverse event. Efficacy measures did not demonstrate any differences between treatment groups. During the open-label trial, 2 additional patients reached a therapeutic concentration. Ranolazine in PAH appears safe, without acute hemodynamic effects after a 500-mg dose. Ranolazine administrated to PAH patients receiving background PAH therapies did not consistently reach therapeutic levels. Future studies should first perform PK analysis in PAH patients receiving PAH therapies and explore the safety and tolerability of the higher doses perhaps necessary to achieve therapeutic levels in PAH patients. (Trial registration: Clinicaltrials.gov identifier NCT01757808.) PMID:26697176

  8. The heart and pulmonary arterial hypertension in systemic sclerosis.

    PubMed

    Vandecasteele, Els H; De Pauw, Michel; Brusselle, Guy; Decuman, Saskia; Piette, Yves; De Keyser, Filip; Smith, V

    2016-02-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of the skin and visceral organs (gastrointestinal tract, heart, kidneys and lungs). Although the prevalence is low, SSc is a disease with high morbidity and mortality. Since pulmonary arterial hypertension (PAH) associated with SSc (SSc-PAH) and clinically evident cardiac involvement is associated with increased mortality, the cardiac complications and PAH in SSc are reviewed. Both diffuse cutaneous (DcSSc) and limited cutaneous (LcSSc) subgroups are at risk for cardiac involvement and SSc-PAH. Cardiac involvement can be divided in pericardial involvement, myocardial involvement and rhythm disturbances and mostly occurs asymptomatically. However, when symptomatic, it is associated with a poor prognosis. Screening for asymptomatic cardiac involvement should be considered in SSc in order to initiate treatment in an early stage. However, there are no randomized controlled trials on treatment options for cardiac involvement in SSc. SSc-PAH is a devastating complication of SSc, which can develop early in DcSSc and LcSSc. Screening for PAH should be performed since screening leads to earlier diagnosis and earlier treatment is associated with a better prognosis. Today, screening is performed by clinical judgement and echocardiography. Recently the DETECT algorithm, a 2-step screening algorithm is proposed in a SSc-subgroup at increased risk for PAH, but further validation is needed. Despite current treatment options with prostacyclins, endothelin-1 receptor antagonists and phosphodiesterase type-5 inhibitors, mortality remains high. Several promising new treatment options for PAH are evaluated in phase II and III clinical trials. PMID:27075793

  9. Noninvasive pulmonary artery wave intensity analysis in pulmonary hypertension

    PubMed Central

    Quail, Michael A.; Knight, Daniel S.; Steeden, Jennifer A.; Taelman, Liesbeth; Moledina, Shahin; Taylor, Andrew M.; Segers, Patrick; Coghlan, Gerry J.

    2015-01-01

    Pulmonary wave reflections are a potential hemodynamic biomarker for pulmonary hypertension (PH) and can be analyzed using wave intensity analysis (WIA). In this study we used pulmonary vessel area and flow obtained using cardiac magnetic resonance (CMR) to implement WIA noninvasively. We hypothesized that this method could detect differences in reflections in PH patients compared with healthy controls and could also differentiate certain PH subtypes. Twenty patients with PH (35% CTEPH and 75% female) and 10 healthy controls (60% female) were recruited. Right and left pulmonary artery (LPA and RPA) flow and area curves were acquired using self-gated golden-angle, spiral, phase-contrast CMR with a 10.5-ms temporal resolution. These data were used to perform WIA on patients and controls. The presence of a proximal clot in CTEPH patients was determined from contemporaneous computed tomography/angiographic data. A backwards-traveling compression wave (BCW) was present in both LPA and RPA of all PH patients but was absent in all controls (P = 6e−8). The area under the BCW was associated with a sensitivity of 100% [95% confidence interval (CI) 63–100%] and specificity of 91% (95% CI 75–98%) for the presence of a clot in the proximal PAs of patients with CTEPH. In conclusion, WIA metrics were significantly different between patients and controls; in particular, the presence of an early BCW was specifically associated with PH. The magnitude of the area under the BCW showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the noninvasive assessment of PH. PMID:25659483

  10. Noninvasive pulmonary artery wave intensity analysis in pulmonary hypertension.

    PubMed

    Quail, Michael A; Knight, Daniel S; Steeden, Jennifer A; Taelman, Liesbeth; Moledina, Shahin; Taylor, Andrew M; Segers, Patrick; Coghlan, Gerry J; Muthurangu, Vivek

    2015-06-15

    Pulmonary wave reflections are a potential hemodynamic biomarker for pulmonary hypertension (PH) and can be analyzed using wave intensity analysis (WIA). In this study we used pulmonary vessel area and flow obtained using cardiac magnetic resonance (CMR) to implement WIA noninvasively. We hypothesized that this method could detect differences in reflections in PH patients compared with healthy controls and could also differentiate certain PH subtypes. Twenty patients with PH (35% CTEPH and 75% female) and 10 healthy controls (60% female) were recruited. Right and left pulmonary artery (LPA and RPA) flow and area curves were acquired using self-gated golden-angle, spiral, phase-contrast CMR with a 10.5-ms temporal resolution. These data were used to perform WIA on patients and controls. The presence of a proximal clot in CTEPH patients was determined from contemporaneous computed tomography/angiographic data. A backwards-traveling compression wave (BCW) was present in both LPA and RPA of all PH patients but was absent in all controls (P = 6e(-8)). The area under the BCW was associated with a sensitivity of 100% [95% confidence interval (CI) 63-100%] and specificity of 91% (95% CI 75-98%) for the presence of a clot in the proximal PAs of patients with CTEPH. In conclusion, WIA metrics were significantly different between patients and controls; in particular, the presence of an early BCW was specifically associated with PH. The magnitude of the area under the BCW showed discriminatory capacity for the presence of proximal PA clot in patients with CTEPH. We believe that these results demonstrate that WIA could be used in the noninvasive assessment of PH. PMID:25659483

  11. Pulmonary arterial hypertension associated with congenital heart disease. Personal perspectives.

    PubMed

    Nakanishi, Toshio

    2015-01-01

    The management of patients with congenital heart disease (CHD) and pulmonary arterial hypertension (PAH) has changed dramatically with the development of targeted therapy with selective pulmonary vasodilators. The number of adult Japanese patients with PAH associated with CHD is increasing. It is important to develop evidence-based guidelines for the management of these patients, and to achieve this, a register of adult Japanese patients with PAH associated with CHD should be established. At the World Symposium in Nice, France, in 2013, the consensus was reached that patients with a pulmonary resistance of < 4 Wood Units (WU)·m(2) have operable disease, and patients with a pulmonary resistance of > 8 WU·m(2) have inoperable disease. However, these criteria are conservative. Some patients with a pulmonary resistance of > 8 WU·m(2) and a good response to a pulmonary vasodilator test have operable disease and a favorable clinical course long after repair of CHD. The criteria determining operability in patients with PAH associated with CHD in the era of pulmonary vasodilators should be established using data obtained from patient registers and/or multicenter studies. The optimal management of Eisenmenger syndrome should also be established using data obtained from patient registers. Prospective studies should be conducted to determine the life expectancy of patients with Eisenmenger syndrome in the era of targeted therapy. A relatively mild increase in pulmonary resistance may result in failure of a Fontan circulation. The effects of pulmonary vasodilators on the long-term prognosis of patients who have undergone the Fontan operation are still unclear. PMID:25787791

  12. Histone deacetylation contributes to low extracellular superoxide dismutase expression in human idiopathic pulmonary arterial hypertension.

    PubMed

    Nozik-Grayck, Eva; Woods, Crystal; Stearman, Robert S; Venkataraman, Sujatha; Ferguson, Bradley S; Swain, Kalin; Bowler, Russell P; Geraci, Mark W; Ihida-Stansbury, Kaori; Stenmark, Kurt R; McKinsey, Timothy A; Domann, Frederick E

    2016-07-01

    Epigenetic mechanisms, including DNA methylation and histone acetylation, regulate gene expression in idiopathic pulmonary arterial hypertension (IPAH). These mechanisms can modulate expression of extracellular superoxide dismutase (SOD3 or EC-SOD), a key vascular antioxidant enzyme, and loss of vascular SOD3 worsens outcomes in animal models of pulmonary arterial hypertension. We hypothesized that SOD3 gene expression is decreased in patients with IPAH due to aberrant DNA methylation and/or histone deacetylation. We used lung tissue and pulmonary artery smooth muscle cells (PASMC) from subjects with IPAH at transplantation and from failed donors (FD). Lung SOD3 mRNA expression and activity was decreased in IPAH vs. FD. In contrast, mitochondrial SOD (Mn-SOD or SOD2) protein expression was unchanged and intracellular SOD activity was unchanged. Using bisulfite sequencing in genomic lung or PASMC DNA, we found the methylation status of the SOD3 promoter was similar between FD and IPAH. Furthermore, treatment with 5-aza-2'-deoxycytidine did not increase PASMC SOD3 mRNA, suggesting DNA methylation was not responsible for PASMC SOD3 expression. Though total histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity, acetylated histones, and acetylated SP1 were similar between IPAH and FD, treatment with two selective class I HDAC inhibitors increased SOD3 only in IPAH PASMC. Class I HDAC3 siRNA also increased SOD3 expression. Trichostatin A, a pan-HDAC inhibitor, decreased proliferation in IPAH, but not in FD PASMC. These data indicate that histone deacetylation, specifically via class I HDAC3, decreases SOD3 expression in PASMC and HDAC inhibitors may protect IPAH in part by increasing PASMC SOD3 expression. PMID:27233998

  13. Diagnostic and therapeutic strategies for resistant arterial hypertension--focus on countries with emerging economies.

    PubMed

    Zhanatbekova, A K; Karazhanova, L K; Begalina, A M; Filipova, S

    2014-01-01

    Arterial hypertensionis an important worldwide health problem. Its relevance relates both to the high incidence and prevalence in all adult communities and to the high risk of serious and potentially fatal cardiovascular events due to hypertension. Resistant hypertension is defined as a blood pressure (BP) remaining above goal (>140/90 mm Hg) despite the use of at least 3 optimally dosed antihypertensive drugs from different classes, with one of the drugs being a diuretic. The exact prevalence of RH is unknown, but it is generally estimated at 10-20% of hypertensive patients. The aim of this review article is to address several important issues: (1) How to diagnose true RH ? (2) What is the optimal state-of-art management of RH in the light of the most recent scientific evidence and what is the role of various medical specialties in this process ? (3) Are there any country specific issues related to diagnosing and treating of RH in Kazakhstan and if so, how to tackle them ?Long-lasting resistant hypertension increases by 50-80% the risk of major cardiovascular events (myocardial infarction, stroke) and end-organ damage. (heart failure, vascular dementia, chronic kidney disease). Adherence to well chosen therapy is the key factor in achieving blood pressure control and this must be based on adequate patient education and universal access to drug therapy. Thus, early recognition and appropriate management of RH must be among the top priorities of all public health initiatives to reduce the burden of cardiovascular diseases (Tab. 2, Fig. 1, Ref. 31). PMID:24836409

  14. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment.

    PubMed

    Lee, Jae Chul; Kim, Kwan Chang; Choe, Soo Young; Hong, Young Mi

    2016-03-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  15. Reduced immunoreactivities of B-type natriuretic peptide in pulmonary arterial hypertension rats after ranolazine treatment

    PubMed Central

    Lee, Jae Chul; Kim, Kwan Chang

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a severe pulmonary vascular disease characterized by sustained increase in the pulmonary arterial pressure and excessive thickening and remodeling of the distal small pulmonary arteries. During disease progression, structural remodeling of the right ventricular (RV) impairs pump function, creates pro-arrhythmic substrates and triggers for arrhythmias. Notably, RV failure and lethal arrhythmias are major contributors to cardiac death in PAH that are not directly addressed by currently available therapies. Ranolazine (RAN) is an anti-anginal, anti-ischemic drug that has cardioprotective effects of heart dysfunction. RAN also has anti-arrhythmic effects due to inhibition of the late sodium current in cardiomyocytes. Therefore, we hypothesized that RAN could reduce the mal-adaptive structural remodeling of the RV, and prevent triggered ventricular arrhythmias in the monocrotaline-induced rat model of PAH. RAN reduced ventricular hypertrophy, reduced levels of B-type natriuretic peptide, and decreased the expression of fibrosis. In addition, RAN prevented cardiovascular death in rat model of PAH. These results support the notion that RAN can improve the functional properties of the RV, highlighting its potential benefits in the setting of heart impairment. PMID:27051563

  16. Calcium antagonist verapamil prevented pulmonary arterial hypertension in broilers with ascites by arresting pulmonary vascular remodeling.

    PubMed

    Yang, Ying; Qiao, Jian; Wang, Huiyu; Gao, Mingyu; Ou, Deyuan; Zhang, Jianjun; Sun, Maohong; Yang, Xin; Zhang, Xiaobo; Guo, Yuming

    2007-04-30

    Calcium signaling has been reported to be involved in the pathogenesis of hypertension. Verapamil, one of the calcium antagonists, is used to characterize the role of calcium signaling in the development of pulmonary arterial hypertension syndrome in broilers. The suppression effect of verapamil on pulmonary arterial hypertension and pulmonary vascular remodeling was examined in broilers, from the age of 16 days to 43 days. Our results showed that oral administration of lower dose of verapamil (5 mg/kg body weight every 12 h) prevented the mean pulmonary arterial pressure, the ascites heart index and the erythrocyte packed cell volume of birds at low temperature from increasing, the heart rate from decreasing, and pulmonary arteriole median from thickening, and no pulmonary arteriole remodeling in broilers treated with the two doses of verapamil at low temperature was observed. Our results indicated that calcium signaling was involved in the development of broilers' pulmonary arterial hypertension, which leads to the development of ascites, and we suggest that verapamil may be used as a preventive agent to reduce the occurrence and development of pulmonary arterial hypertension in broilers. PMID:17320074

  17. Arterial hypertension in children with hemolytic uremic syndrome after kidney transplantation.

    PubMed

    Hoenecke, Johannes; Hartmann, Hans; Melk, Anette

    2015-08-01

    The development of arterial hypertension after KTX is a well-known complication. HUS is a systemic disease associated with arterial hypertension during long-term follow-up. Our goal was to report on the severity of arterial hypertension after KTX in patients with typical and atypical HUS. We analyzed the course of 197 patients with HUS, of which 22 (n = 10 with typical HUS; n = 12 with atypical HUS) developed ESRF and received KTX as renal replacement therapy. We analyzed data from 1766 casual BP and 85 24-h ABPM measurements. In addition, we evaluated the used antihypertensive strategy. Comparison between the two patient groups revealed that patients with atypical HUS had significantly higher casual SBP-SDS and DBP-SDS values after KTX despite similar intensity of antihypertensive treatment. These data were supported by analysis of ABPM profiles showing comparable results for the interval 1-5 yr after KTX. Patients with atypical HUS had a greater severity of arterial hypertension despite similar treatment strategies and intensity of treatment. Our observation, even though in a small cohort, supports recent genetic studies showing arterial hypertension closely associated with HUS-causing mutations in patients with atypical HUS. PMID:26073101

  18. 17β-Estradiol Attenuates Conduit Pulmonary Artery Mechanical Property Changes With Pulmonary Arterial Hypertension.

    PubMed

    Liu, Aiping; Tian, Lian; Golob, Mark; Eickhoff, Jens C; Boston, Madison; Chesler, Naomi C

    2015-11-01

    Pulmonary arterial hypertension (PAH), a rapidly fatal vascular disease, strikes women more often than men. Paradoxically, female PAH patients have better prognosis and survival rates than males. The female sex hormone 17β-estradiol has been linked to the better outcome of PAH in females; however, the mechanisms by which 17β-estradiol alters PAH progression and outcomes remain unclear. Because proximal pulmonary arterial (PA) stiffness, one hallmark of PAH, is a powerful predictor of mortality and morbidity, we hypothesized that 17β-estradiol attenuates PAH-induced changes in mechanical properties in conduit proximal PAs, which imparts hemodynamic and energetic benefits to right ventricular function. To test this hypothesis, female mice were ovariectomized and treated with 17β-estradiol or placebo. PAH was induced in mice using SU5416 and chronic hypoxia. Extra-lobar left PAs were isolated and mechanically tested ex vivo to study both static and frequency-dependent mechanical behaviors in the presence or absence of smooth muscle cell activation. Our static mechanical test showed significant stiffening of large PAs with PAH (P<0.05). 17β-Estradiol restored PA compliance to control levels. The dynamic mechanical test demonstrated that 17β-estradiol protected the arterial wall from the PAH-induced frequency-dependent decline in dynamic stiffness and loss of viscosity with PAH (P<0.05). As demonstrated by the in vivo measurement of PA hemodynamics via right ventricular catheterization, modulation by 17β-estradiol of mechanical proximal PAs reduced pulsatile loading, which contributed to improved ventricular-vascular coupling. This study provides a mechanical mechanism for delayed disease progression and better outcome in female PAH patients and underscores the therapeutic potential of 17β-estradiol in PAH. PMID:26418020

  19. Stiffening of the Extrapulmonary Arteries From Rats in Chronic Hypoxic Pulmonary Hypertension.

    PubMed

    Drexler, E S; Bischoff, J E; Slifka, A J; McCowan, C N; Quinn, T P; Shandas, R; Ivy, D D; Stenmark, K R

    2008-01-01

    Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries. PMID:27096124

  20. Stiffening of the Extrapulmonary Arteries From Rats in Chronic Hypoxic Pulmonary Hypertension

    PubMed Central

    Drexler, E. S; Bischoff, J. E; Slifka, A. J; McCowan, C. N; Quinn, T. P; Shandas, R; Ivy, D. D; Stenmark, K. R

    2008-01-01

    Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries. PMID:27096124

  1. Arterial Hypertension Is Characterized by Imbalance of Pro-Angiogenic versus Anti-Angiogenic Factors

    PubMed Central

    Marek-Trzonkowska, Natalia; Kwieczyńska, Anna; Reiwer-Gostomska, Magdalena; Koliński, Tomasz; Molisz, Andrzej; Siebert, Janusz

    2015-01-01

    Objective Hypertension is the most common cardiovascular disease and the main risk factor for stroke, peripheral arterial disease, arterial aneurysms and kidney disease. It has been reported recently that hypertensive patients and animals are characterized by decreased density of arterioles and capillaries in the tissues, called rarefaction. Rarefaction significantly increases peripheral resistance which results in elevated blood pressure, leads to vessel damage and induction of inflammation. Therefore, we hypothesized that hypertension is associated with decreased serum concentration of physiological pro-angiogenic factors and concomitant increased production of angiogenesis inhibitors. Materials and Methods 82 patients diagnosed with hypertension and 34 healthy volunteers were recruited to the study. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) techniques were used to measure serum levels of the following cytokines: endostatin, vascular endothelial growth factor (VEGF), interleukin 8 (IL-8), angiogenin, and basic fibroblast growth factor (bFGF). Results Hypertensive patients were characterized by increased serum concentration of endostatin which is an anti-angiogenic factor. In addition, hypertension was associated with decreased levels of physiological pro-angiogenic mediators such as: angiogenin and bFGF. The hypertensive group was also characterized by elevated levels of CRP, VEGF and IL-8 that are the hallmarks of inflammation. Conclusions Presented results show that hypertension is characterized by imbalance of pro-angiogenic and anti-angiogenic factors in the background of inflammation. PMID:25951297

  2. Adult congenital heart disease and pulmonary arterial hypertension: the Texas Adult Congenital Heart Program experience.

    PubMed

    Franklin, Wayne J; Parekh, Dhaval R; Safdar, Zeenat

    2011-11-01

    Congenital heart disease (CHD) is a common structural defect of the heart or major blood vessels. Patients with adult congenital heart disease (ACHD) have medical needs that are distinct from those of pediatric patients with CHD, and the transition into adult health care is important for management of the patient with ACHD. A large proportion of patients with CHD develop diseases and complications associated with the long-term stress of intracardiac shunts. Pulmonary arterial hypertension (PAH) is a significant complication of some CHD lesions. The treatment of these patients remains challenging due to their combined heart and lung disease, and multidisciplinary care is ofen necessitated for a variety of secondary conditions. A number of treatment options are available for the management of PAH associated with CHD, including prostanoids, phosphodiesterase type-5 inhibitors, and endothelin receptor antagonists. This article discusses the diagnosis and management of such ACHD patients with PAH. PMID:22104452

  3. Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension

    PubMed Central

    Farha, Samar; Lichtin, Alan; Graham, Brian; George, Deepa; Aldred, Micheala; Hazen, Stanley L.; Loyd, James; Tuder, Rubin

    2012-01-01

    Hematopoietic myeloid progenitors released into the circulation are able to promote vascular remodeling through endothelium activation and injury. Endothelial injury is central to the development of pulmonary arterial hypertension (PAH), a proliferative vasculopathy of the pulmonary circulation, but the origin of vascular injury is unknown. In the present study, mice transplanted with BM-derived CD133+ progenitor cells from patients with PAH, but not from healthy controls, exhibited morbidity and/or death due to features of PAH: in situ thrombi and endothelial injury, angioproliferative remodeling, and right ventricular hypertrophy and failure. Myeloid progenitors from patients with heritable and/or idiopathic PAH all produced disease in xenografted mice. Analyses of hematopoietic transcription factors and colony formation revealed underlying abnormalities of progenitors that skewed differentiation toward the myeloid-erythroid lineage. The results of the present study suggest a causal role for hematopoietic stem cell abnormalities in vascular injury, right ventricular hypertrophy, and morbidity associated with PAH. PMID:22745307

  4. AMBITION: An important piece in the therapeutic puzzle of pulmonary arterial hypertension

    PubMed Central

    Said, Karim

    2015-01-01

    It is believed that simultaneous targeting of two or more of the three pathogenic pathways of pulmonary arterial hypertension (the endothelin, nitric oxide, and prostacyclin pathways) is associated with additive or synergistic effects with subsequent increasing efficacy and improving outcomes. However, there is lack of evidence to guide the use of combination strategy among pulmonary arterial hypertension patients and many questions remain to be answered. One of these vital questions is whether the strategy of upfront initiation of combination therapy could improve patients outcomes compared to the strategy of initial monotherapy. The recently published AMBITION trial represents an important forward step towards answering this question by comparing a strategy of first-line combination therapy (ambrisentan and tadalafil) versus first-line monotherapy (ambrisentan or tadalafil) in patients with pulmonary arterial hypertension. PMID:26779523

  5. Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats

    PubMed Central

    Girgla, Saavia S.; Moreno, Guillermo; McClain, Jonathon L.; Dorrance, Anne M.

    2014-01-01

    Hypertension causes vascular inflammation evidenced by an increase in perivascular macrophages and proinflammatory cytokines in the arterial wall. Perivascular macrophage depletion reduced tumor necrosis factor (TNF)-α expression in cerebral arteries of hypertensive rats and attenuated inward remodeling, suggesting that TNF-α might play a role in the remodeling process. We hypothesized that TNF-α inhibition would improve middle cerebral artery (MCA) structure and reduce damage after cerebral ischemia in hypertensive rats. Six-week-old male stroke-prone spontaneously hypertensive rats (SHRSP) were treated with the TNF-α inhibitor etanercept (ETN; 1.25 mg·kg−1·day−1 ip daily) or PBS (equivolume) for 6 wk. The myogenic tone generation, postischemic dilation, and passive structure of MCAs were assessed by pressure myography. Cerebral ischemia was induced by MCA occlusion (MCAO). Myogenic tone was unchanged, but MCAs from SHRSP + ETN had larger passive lumen diameter and reduced wall thickness and wall-to-lumen ratio. Cerebral infarct size was increased in SHRSP + ETN after transient MCAO, despite an improvement in dilation of nonischemic MCA. The increase in infarct size was linked to a reduction in the number of microglia in the infarct core and upregulation of markers of classical macrophage/microglia polarization. There was no difference in infarct size after permanent MCAO or when untreated SHRSP subjected to transient MCAO were given ETN at reperfusion. Our data suggests that TNF-α inhibition attenuates hypertensive MCA remodeling but exacerbates cerebral damage following ischemia/reperfusion injury likely due to inhibition of the innate immune response of the brain. PMID:25015967

  6. Renal artery embolization for managing uncontrolled hypertension in a kidney transplant candidate

    PubMed Central

    Alhamid, Naji; Alterky, Hani; Othman, Mohammad Imad

    2013-01-01

    We report a case of pre-operative bilateral renal artery embolization to control the resistant and malignant hypertension in a patient prepared for kidney transplantation. A 34-year-old man with end-stage renal disease as a result of the focal segmental glomerulosclerosis and uncontrolled hypertension that precluded the transplantation surgery and the patient's post-transplant blood pressure and the renal function remained within normal limits following the transplant for 6 months of follow-up. PMID:23984264

  7. Contribution of live heartworms harboring in pulmonary arteries to pulmonary hypertension in dogs with dirofilariasis.

    PubMed

    Kitagawa, H; Sasaki, Y; Ishihara, K; Hirano, Y

    1990-12-01

    To investigate whether adult heartworms harboring in the pulmonary arteries contribute to pulmonary hypertension, we determined the cardio-pulmonary values immediately before and after removal of heartworms from the pulmonary arteries and before and after insertion of live worms in their place. In 10 heartworm-infected dogs, 8 to 46 worms were removed. The mean pulmonary arterial pressure fell significantly from 24.5 +/- 7.9 mmHg to 16.3 +/- 4.9 mmHg (p less than 0.01) immediately after removal. The right cardiac output decreased in 7 of the 10 cases. The total pulmonary resistance and right ventricular stroke work index also decreased. At 24 hours after removal, live heartworms were put back into the pulmonary arteries of their host dog. The mean pulmonary arterial pressure elevated significantly (p less than 0.01) immediately after insertion. The right cardiac output further decreased in 7 of the 10 dogs, and the total pulmonary resistance and right ventricular stroke work index increased. Separate from this, 12 to 42 heartworms were transplanted into the pulmonary arteries of 5 heartworm-free dogs. Immediately after transplantation, the pulmonary arterial pressure did not show any significant change. However, the stroke volume decreased, and the total pulmonary resistance increased. These facts suggest a contribution of live heartworms to the pulmonary hypertension, although there is a complicated interaction among the presence of heartworms, the pulmonary lesions and the pulmonary hypertension. PMID:2287128

  8. Phosphorylation inactivation of endothelial nitric oxide synthesis in pulmonary arterial hypertension.

    PubMed

    Ghosh, Sudakshina; Gupta, Manveen; Xu, Weiling; Mavrakis, Deloris A; Janocha, Allison J; Comhair, Suzy A A; Haque, Mohammad Mahfuzul; Stuehr, Dennis J; Yu, Jun; Polgar, Peter; Naga Prasad, Sathyamangla V; Erzurum, Serpil C

    2016-06-01

    The impairment of vasodilator nitric oxide (NO) production is well accepted as a typical marker of endothelial dysfunction in vascular diseases, including in the pathophysiology of pulmonary arterial hypertension (PAH), but the molecular mechanisms accounting for loss of NO production are unknown. We hypothesized that low NO production by pulmonary arterial endothelial cells in PAH is due to inactivation of NO synthase (eNOS) by aberrant phosphorylation of the protein. To test the hypothesis, we evaluated eNOS levels, dimerization, and phosphorylation in the vascular endothelial cells and lungs of patients with PAH compared with controls. In mechanistic studies, eNOS activity in endothelial cells in PAH lungs was found to be inhibited due to phosphorylation at T495. Evidence pointed to greater phosphorylation/activation of protein kinase C (PKC) α and its greater association with eNOS as the source of greater phosphorylation at T495. The presence of greater amounts of pT495-eNOS in plexiform lesions in lungs of patients with PAH confirmed the pathobiological mechanism in vivo. Transfection of the activating mutation of eNOS (T495A/S1177D) restored NO production in PAH cells. Pharmacological blockade of PKC activity by β-blocker also restored NO formation by PAH cells, identifying one mechanism by which β-blockers may benefit PAH and cardiovascular diseases through recovery of endothelial functions. PMID:27130529

  9. [Arterial hypertension as a medical and social problem in the older urban population. The CINDI WHO Program study].

    PubMed

    Kaczmarczyk-Chałas, Krystyna; Kwaśniewska, Magdalena; Pikala, Małgorzata; Drygas, Wojciech

    2008-01-01

    Increasing lifespan and progressive aging of the Polish population results in rising demands on health care. Chronic diseases with a leading position of arterial hypertension (HA) prevail in morbidity rates of adult seniors. The aim of the study is to characterize hypertension in the elderly with regard to other risk factors, complications and therapeutic control. The study was carried out in 2002 within the framework of the CINDI WHO Programme. A total of 1460 persons were randomly selected among residents of Lodz aged > or = 65 years. The response rate was 57%. All participants underwent questionnaire interview, two blood pressure (BP) measurements, anthropometric and physical examination, ECG and laboratory tests. After final verification, we analysed data collected from 828 persons (289 men and 539 women). Mean values of systolic and diastolic BP were 147.6 and 83.6 mmHg, respectively. The increase of systolic BP with age of studied seniors was observed. Hypertension was diagnosed in 669 persons (79% men, 82% women). In most cases there were systolic-diastolic or isolated systolic hypertension. About 60% of seniors with elevated BP declared suffering from HA, while 73% were under antihypertensive treatment. Normalization of BP (< 140/ 90 mmHg) was achieved in 28% of treated patients. Most often prescribed medications were: ACE-inhibitors (51%), beta-blockers (40%), calcium channel blockers (31%) and diuretics (30%). Mean values of plasma lipids and prevalence of lipid disorders were comparable in hypertensive and normotensive persons. Among patients with HA there were significantly smaller percentage of smokers (8.6% vs 18.7%, p < 0.05). The prevalence of obesity, visceral obesity and metabolic syndrome was higher in hypertensive seniors. As a result, incidents of myocardial infarction and morbidity due to coronary artery disease were twice as cantly more often hospitalised and visited family doctors (7 vs 4.6 visits/year) in comparison to normotensive subjects

  10. [Innovative instruction for assisting patients with arterial hypertension].

    PubMed

    Bontemps, S; Pechère-Bertschi, A

    2015-09-01

    The MOOC In The Heart of Hypertension is an innovative online training for students and health providers. Its aim is to strengthen skills for professionals caring people suffering from hypertension. A MOOC is a free online training aiming unlimited participation. It widely promotes a high quality education. Medical and paramedical training recently seized upon this powerful tool, for initial and continuing training. Indeed, MOOC responds to several pedagogic challenges, particularly through educational strategies focused on the learner's skills: mastery of pedagogy, retrieval practice and peer grading. This MOOC about hypertension aims at responding to the needs of caregivers to enhance their therapeutic support skills. PMID:26540996

  11. Development of pulmonary arterial hypertension during oral dasatinib therapy for chronic myelogenous leukemia.

    PubMed

    Morishita, Sakura; Hagihara, Maki; Itabashi, Megumi; Ishii, Yoshimi; Yamamoto, Wataru; Numata, Ayumi; Motohashi, Kenji; Matsumoto, Kenji; Fujisawa, Shin; Nakajima, Hideaki

    2016-08-01

    We present a 36-year-old woman who had been taking oral dasatinib for 3 years for the treatment of chronic myelogenous leukemia (CML). Although adverse events such as thrombocytopenia and pleural effusion developed, she showed a major molecular response (MMR) 22 months after the initiation of oral dasatinib administration, and the therapy was thus continued. Approximately 34 months after oral dasatinib initiation, she developed severe exertional dyspnea and had to be urgently hospitalized. There was no apparent pleural effusion increase, and neither imaging nor blood test results suggested pneumonia or other infections. Pulmonary arterial hypertension (PAH) was suspected on the basis of transthoracic echocardiography. PAH was then confirmed by right heart catheterization. Though dasatinib was discontinued on the day of hospitalization, pulmonary hypertension and heart failure progressed, and she did not respond to catecholamines or PDE5 (phosphodiesterase type 5) inhibitors. On the 4(th) hospital day, she experienced cardiopulmonary arrest and died 1 week later. Cases with PAH due to oral administration of dasatinib have been reported previously. However, cases showing the rapid progression documented in our patient are rare and we advocate that PAH be considered a potential adverse event associated with dasatinib therapy. PMID:27599415

  12. Transcatheter Embolization of Pulmonary Artery False Aneurysm Associated with Primary Pulmonary Hypertension

    SciTech Connect

    Hiraki, T. Kanazawa, S.; Mimura, H.; Yasui, K.; Okumura, Y.; Dendo, S.; Yoshimura, K.; Takahara, M.; Hiraki, Y.

    2004-03-15

    A 29-year-old woman with primary pulmonary hypertension presented with recurrent hemoptysis. Contrast-enhanced CT of the chest demonstrated the enhanced mass surrounded by consolidation related to parenchymal hemorrhage. Pulmonary angiography suggested that the mass was a pulmonary artery false aneurysm. After a microcatheter was superselectively inserted into the parent artery of the falseaneurysm, the false aneurysm was successfully treated by transcatheterembolization with coils. Her hemoptysis has never recurred.

  13. Increased rhythmicity in hypertensive arterial smooth muscle is linked to transient receptor potential canonical channels.

    PubMed

    Chen, Xiaoping; Yang, Dachun; Ma, Shuangtao; He, Hongbo; Luo, Zhidan; Feng, Xiaoli; Cao, Tingbing; Ma, Liqun; Yan, Zhencheng; Liu, Daoyan; Tepel, Martin; Zhu, Zhiming

    2010-10-01

    Vasomotion describes oscillations of arterial vascular tone due to synchronized changes of intracellular calcium concentrations. Since increased calcium influx into vascular smooth muscle cells from spontaneously hypertensive rats (SHR) has been associated with variances of transient receptor potential canonical (TRPC) channels, in the present study we tested the hypothesis that increased vasomotion in hypertension is directly linked to increased TRPC expression. Using a small vessel myograph we observed significantly increased norepinephrine-induced vasomotion in mesenteric arterioles from SHR compared to normotensive Wistar-Kyoto (WKY) rats. Using immunoblottings we obtained significantly increased expression of TRPC1, TRPC3 and TRPC5 in mesenteric arterioles from SHR compared to WKY, whereas TRPC4 and TRPC6 showed no differences. Norepinephrine-induced vasomotion from SHR was significantly reduced in the presence of verapamil, SKF96365, 2-aminoethoxydiphenylborane (2-APB) or gadolinium. Pre-incubation of mesenteric arterioles with anti-TRPC1 and anti-TRPC3 antibodies significantly reduced norepinephrine-induced vasomotion and calcium influx. Control experiments with pre-incubation of TRPC antibodies plus their respective antigenic peptide or in the presence of anti-β-actin antibodies or random immunoglobulins not related to TRPC channels showed no inhibitory effects of norepinephrine-induced vasomotion and calcium influx. Administration of candesartan or telmisartan, but not amlodipine to SHR for 16 weeks significantly reduced either the expression of TRPC1, TRPC3 and TRPC5 as well as norepinephrine-induced vasomotion in mesenteric arterioles. In conclusion we gave experimental evidence that the increased TRPC1, TRPC3 and TRPC5 expression in mesenteric arterioles from SHR causes increased vasomotion in hypertension. PMID:19725917

  14. Renovascular hypertension

    MedlinePlus

    Renal hypertension; Hypertension - renovascular; Renal artery occlusion; Stenosis - renal artery; Renal artery stenosis ... blood pressure to rise. Risk factors for atherosclerosis: High blood pressure Smoking Diabetes High cholesterol Heavy alcohol use Cocaine ...

  15. Multiple Giant Splenic Artery Aneurysms Causing Sinistral (Left-Sided) Portal Hypertension

    PubMed Central

    Beksac, Kemal; Karakoc, Derya

    2016-01-01

    Background. Splenic artery aneurysm is the most common type of visceral aneurysms. They are usually asymptomatic and have a potential for rupture and therefore life-threatening hemorrhage. It is rare for them to cause sinistral portal hypertension. Case Report. A 23-year-old female patient presented to our clinic with gastric varices, splenomegaly, pancytopenia, and normal liver functions. She was thus diagnosed with left-sided portal hypertension. Radiologic evaluation showed splenomegaly, splenic vein obstruction, and multiple aneurysms along the splenic artery ranging from 2.5 cm to 7 cm. Splenic artery aneurysm was thought to be the cause of portal hypertension and hypersplenism. We decided splenectomy is the best course of treatment. Pancytopenia could not be corrected preoperatively despite the transfusion treatment. Surgical exploration revealed multiple aneurysms deeply embedded in pancreas. Thrombocyte and erythrocyte transfusion was performed after splenic artery ligation to correct pancytopenia before further intervention. Splenic artery, spleen, and distal pancreas were resected en bloc. Patient's blood parameters became normal within first postoperative day. Patient had an uneventful postoperative course and was discharged without incident. Conclusion. Splenic artery aneurysms are rare but potentially life-threatening incidents. Therefore, it is important to know the unusual presentations and prepare accordingly. PMID:27110411

  16. Plasma endothelin-1 levels in patients with systemic sclerosis: influence of pulmonary or systemic arterial hypertension.

    PubMed Central

    Morelli, S; Ferri, C; Di Francesco, L; Baldoncini, R; Carlesimo, M; Bottoni, U; Properzi, G; Santucci, A

    1995-01-01

    OBJECTIVES--To investigate the behaviour of circulating endothelin-1 (ET-1) in patients affected by systemic sclerosis and to elucidate the relationship between systemic and pulmonary plasma peptide and arterial pressure levels. METHODS--Plasma ET-1 concentrations were determined in 48 patients affected by systemic sclerosis (41 women, seven men; mean age 47.2 (SD 5.5) years) with or without systemic or pulmonary hypertension (or both). A group of 18 normal volunteers served as controls (15 women, three men; mean age 45.0 (10.1) years). RESULTS--Plasma ET-1 levels were significantly greater in patients affected by systemic sclerosis (1.65 (0.29) pg/ml) than in controls (0.63 (0.19) pg/ml) (p < 0.0001). Pulmonary artery systolic hypertension alone was present in 14 patients with systemic sclerosis (50.5 (8.49) mm Hg, range 37-67 mm Hg), and systemic hypertension alone (160.7 (5.9)/100.6 (3.2) mm Hg) was present in 11 patients. Both conditions were present in 12 patients, while 11 patients had systemic hypertension. There were no significant differences in plasma ET-1 levels between patients with pulmonary hypertension alone (1.62 (0.21) pg/ml) and those with systemic hypertension alone (1.65 (0.43) pg/ml). In particular, patients with normal pulmonary artery and systemic pressures (n = 11) had plasma ET-1 concentrations identical to those found in patients (n = 12) with both pulmonary and systemic hypertension (1.70 (0.15) v 1.64 (0.35) pg/ml, respectively). No correlations were observed between plasma ET-1 and either pulmonary or systemic pressures. CONCLUSION--Systemic sclerosis is characterised by increased plasma ET-1 levels, but neither pulmonary nor systemic hypertension are accompanied by further increase in plasma peptide levels. PMID:7495344

  17. RNA Sequencing Analysis Detection of a Novel Pathway of Endothelial Dysfunction in Pulmonary Arterial Hypertension

    PubMed Central

    Rhodes, Christopher J.; Im, Hogune; Cao, Aiqin; Hennigs, Jan K.; Wang, Lingli; Sa, Silin; Chen, Pin-I; Nickel, Nils P.; Miyagawa, Kazuya; Hopper, Rachel K.; Tojais, Nancy F.; Li, Caiyun G.; Gu, Mingxia; Spiekerkoetter, Edda; Xian, Zhaoying; Chen, Rui; Zhao, Mingming; Kaschwich, Mark; del Rosario, Patricia A.; Bernstein, Daniel; Zamanian, Roham T.; Wu, Joseph C.; Snyder, Michael P.

    2015-01-01

    Rationale: Pulmonary arterial hypertension is characterized by endothelial dysregulation, but global changes in gene expression have not been related to perturbations in function. Objectives: RNA sequencing was used to discriminate changes in transcriptomes of endothelial cells cultured from lungs of patients with idiopathic pulmonary arterial hypertension versus control subjects and to assess the functional significance of major differentially expressed transcripts. Methods: The endothelial transcriptomes from the lungs of seven control subjects and six patients with idiopathic pulmonary arterial hypertension were analyzed. Differentially expressed genes were related to bone morphogenetic protein type 2 receptor (BMPR2) signaling. Those down-regulated were assessed for function in cultured cells and in a transgenic mouse. Measurements and Main Results: Fold differences in 10 genes were significant (P < 0.05), four increased and six decreased in patients versus control subjects. No patient was mutant for BMPR2. However, knockdown of BMPR2 by siRNA in control pulmonary arterial endothelial cells recapitulated 6 of 10 patient-related gene changes, including decreased collagen IV (COL4A1, COL4A2) and ephrinA1 (EFNA1). Reduction of BMPR2-regulated transcripts was related to decreased β-catenin. Reducing COL4A1, COL4A2, and EFNA1 by siRNA inhibited pulmonary endothelial adhesion, migration, and tube formation. In mice null for the EFNA1 receptor, EphA2, versus control animals, vascular endothelial growth factor receptor blockade and hypoxia caused more severe pulmonary hypertension, judged by elevated right ventricular systolic pressure, right ventricular hypertrophy, and loss of small arteries. Conclusions: The novel relationship between BMPR2 dysfunction and reduced expression of endothelial COL4 and EFNA1 may underlie vulnerability to injury in pulmonary arterial hypertension. PMID:26030479

  18. Therapies for pulmonary arterial hypertension: where are we today, where do we go tomorrow?

    PubMed

    Seferian, Andrei; Simonneau, Gérald

    2013-09-01

    Pulmonary arterial hypertension (PAH) is a progressive disease characterised by remodelling of small pulmonary arteries leading to an increased pulmonary vascular resistance, right ventricular failure and death. Available treatments try to re-establish the equilibrium on three signalling pathways: the prostacyclin, the endothelin (ET)-1 and the nitric oxide. Prostanoids, such as epoprostenol or treprostinil have a vasodilator, antiproliferative and immunomodulatory effect and, despite the administration inconveniences, represent established therapies for severe cases of PAH. Recently oral prostacyclin receptor agonists have shown encouraging results. Many clinical studies targeting the vasoconstrictor ET-1 pathway with receptor antagonists like bosentan and ambrisentan have shown strong results, even more optimism coming from macitentan, the newest drug. Sildenafil and tadalafil, two phosphodiesterase type-5 inhibitors, have shown improved exercise capacity by increasing the nitric oxide level. Riociguat, acting on the same nitric oxide pathway, as a guanylatecyclase activator, has shown promising results in clinical trials and will be available soon. Long-awaited results for tyrosin-kinase inhibitor, imatinib, as an antiproliferative therapy in PAH have been disappointing, due to severe adverse events. In conclusion, although it remains a disease with severe prognosis, the past 20 years have represented a huge progress in terms of treatments for PAH with interesting opportunities for the future. PMID:23997048

  19. [Regional characteristics of arterial hypertension in adult population of Croatia].

    PubMed

    Erceg, Marijan; Hrabak-Zerjavić, Vlasta; Ivicević Uhernik, Ana

    2007-06-01

    between the east and south, west and City of Zagreb should be investigated. In the high blood pressure group, 76.5% of subjects had a body mass index greater than 25 and 48% ofthose with inadequate physical activity, both exceeding the rates recorded in persons with normal blood pressure. Whereas 58.6% of the subjects knew they had elevated blood pressure, 48.4% of them were taking their therapy, and only 14.8% kept their blood pressure under control (systolic <140 mm Hg and diastolic <90 mm Hg). Arterial hypertension is a major public health problem in all regions of Croatia. The available literature data suggest that the Croatia's share of individuals with high blood pressure is comparable to that in industrialized countries of continental Europe. The prevention of excessive body weight, also through increased physical activity of the population and changes in poor dietary habits, remains the essential element in planning primary prevention programs for high blood pressure. Raising the population's awareness of the problem, early detection of high blood pressure and encouraging the population to take regular therapy for high blood pressure, along with the adoption of healthy lifestyle are important factors in achieving effective control and alleviating the consequences of hypertension. PMID:17629105

  20. Endothelium-derived Relaxing Factors of Small Resistance Arteries in Hypertension

    PubMed Central

    2014-01-01

    Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions. PMID:25343007

  1. Mediastinal lymphadenopathy and pulmonary arterial hypertension in mixed connective tissue disease

    SciTech Connect

    Guit, G.L.; Shaw, P.C.; Ehrlich, J.; Kroon, H.M.; Oudkerk, M.

    1985-02-01

    A case of mixed connective tissue disease (MCTD) is presented in which mediastinal lymphadenopathy was the most prominent radiological finding detected by plain chest radiographs and computed tomography. Pulmonary arterial hypertension, which is a rare and often fatal complication of MCTD, also developed in this patient.

  2. [Role of ophthalmoscopy in arterial hypertension: a problem revisited].

    PubMed

    Palatini, P; Penzo, M; Bongiovì, S; Canali, C; Pessina, A C

    1991-09-01

    To evaluate the present role of fundal examination in the assessment of the hypertensive patient, 348 hypertensive subjects, mostly with borderline or mild hypertension, were studied with direct ophthalmoscopy. The exam was always performed by the same observer. The degree of left ventricular hypertrophy was also evaluated with ECG and echocardiography. Blood pressure was measured with 24-hour ambulatory monitoring, using either the Del Mar Avionics Pressurometer II and IV, the Spacelabs 5200 or the A & D TM-2420. Signs of hypertensive retinopathy were found in 51% of the subjects. The degree of retinopathy, defined according to a modified Keith-Wagener grading system, was highly correlated with average 24-hour mean blood pressure (r = 0.31; p less than 0.0001). Based on ECG, 16% of the subjects had left ventricular hypertrophy, while 23% showed an echocardiographic left ventricular mass, indexed by body surface area, above the normal limits. Left ventricular mass index was correlated with ambulatory blood pressure levels, but at a lower level of statistical significance (r = 0.19; p less than 0.001) compared to the degree of retinopathy. No correlation was found between 24-hour blood pressure and ECG findings. Ophthalmoscopy proved to be more sensitive than echocardiography and ECG in indexing 24-hour blood pressure load, while the specificity of the 3 exams was similar. The present data indicate that fundal examination is a sensitive indicator of the vascular consequences of increased blood pressure and is therefore useful in the assessment of the hypertensive patient, while the more expensive echocardiography is not of great clinical value in borderline and mild hypertension. PMID:1839370

  3. [CHANGES IN THE METABOLISM IN THE MYOCARDIUM OF RATS WITH ARTERIAL HYPERTENSION].

    PubMed

    Dovgan, R S; Zagorodnyi, M I

    2015-01-01

    In the myocardium of the rats with arterial hypertension marked increase in the amount of unsaturated fatty acids and polyunsaturated fatty acids. Reducing the concentration of palmitic acid and increased levels of arachidonic acid is considered as one of the factors that lead to the development of energy deficit and oxidative stress. In rats, with hypertension myocardial lactate concentration increases in the cytoplasmic fraction and reducing the amount of ATP. The level in the cytoplasmic and mitochondrial fractions above benchmarks, indicating about the change of antioxidant systems of the body In the cytoplasm and mitochondria of cardiomyocytes of the rats with arterial hypertension marked decrease in the activity of antioxidant enzymes: NO-synthase, catalase, glutathione reductase, which causes metabolic changes of the myocardium. PMID:27491168

  4. Effect of eplerenone on the severity of obstructive sleep apnea and arterial stiffness in patients with resistant arterial hypertension.

    PubMed

    Krasińska, Beata; Miazga, Angelika; Cofta, Szczepan; Szczepaniak-Chicheł, Ludwina; Trafas, Tomasz; Krasiński, Zbigniew; Pawlaczyk-Gabriel, Katarzyna; Tykarski, Andrzej

    2016-05-27

    INTRODUCTION    Obstructive sleep apnea (OSA) is considered to be one of the major causes of resistant arterial hypertension (RAH). Apnea episodes cause hypoxia, which triggers the activation of the renin-angiotensin-aldosterone system. This leads to water retention and swelling in the neck region, exacerbating OSA symptoms. It is assumed that the use of eplerenone may reduce the swelling and thus alleviate the severity of OSA. OBJECTIVES    We aimed to prospectively assess the impact of eplerenone on the severity of OSA and arterial stiffness in patients with RAH. PATIENTS AND METHODS    The study included 31 patients with RAH and OSA. The exclusion criteria were as follows: secondary hypertension, myocardial infarction, stroke 6 months prior to the study, congestive heart failure, chronic kidney failure, alcohol or drug addiction, and active cancer. In all patients, the following tests were performed: blood pressure (BP) measurement (traditionally and using ambulatory BP measuring [ABPM]), applanation tonometry, polysomnography, and the apnea-hypopnea index (AHI) calculation. The tests were done before and after 3 months of eplerenone therapy. Patients received 50 mg of oral eplerenone daily, along with other hypertensive drugs. RESULTS    The mean age of participants was 57.76 ±6.16 years. After 3 months of eplerenone therapy, we observed a significant reduction in the AHI, neck circumference, BP, aortic pulse wave, and arterial wall stiffness. There were significant correlations between the AHI and mean BP measured by ABPM and between the AHI and arterial stiffness parameters. CONCLUSIONS    Our results provide evidence for the clinical significance of eplerenone, not only as an antihypertensive medication but also as a drug that may reduce the severity of OSA and arterial stiffness in patients with RAH and OSA. PMID:27230560

  5. Rescue baroreflex activation therapy after Stanford B aortic dissection due to therapy-refractory hypertension.

    PubMed

    Weipert, Kay F; Most, Astrid; Dörr, Oliver; Helmig, Inga; Elzien, Meshal; Krombach, Gabriele; Hamm, Christian W; Erkapic, Damir; Schmitt, Joern

    2016-06-01

    Clinical trials have demonstrated significant and durable reduction in arterial pressure from baroreflex activation therapy (BAT) in patients with resistant arterial hypertension. There is a lack of data, however, concerning the use of BAT in a rescue approach during therapy-refractory hypertensive crisis resulting in life-threatening end-organ damage. Here, we describe the first case in which BAT was applied as a rescue procedure in an intensive care setting after ineffective maximum medical treatment. A 34-year-old male patient presented with Stanford B aortic dissection and hypertensive crisis. The dissection membrane extended from the left subclavian artery down to the right common iliac artery, resulting in a total arterial occlusion of the right leg. After emergency thoracic endovascular aortic repair and femorofemoral crossover bypass, the patient developed a compartment syndrome of the right lower limb, ultimately leading to amputation of the right leg above the knee. Even under deep sedation recurrent hypertensive crises of up to 220 mm Hg occurred that could not be controlled by eight antihypertensive drugs of different classes. Screening for secondary hypertension was negative. Eventually, rescue implantation of right-sided BAT was performed as a bailout procedure, followed by immediate activation of the device. After a hospital stay of a total of 8 weeks, the patient was discharged 2 weeks after BAT initiation with satisfactory blood pressure levels. After 1-year follow-up, the patient has not had a hypertensive crisis since the onset of BAT and is currently on fourfold oral antihypertensive therapy. The previously described bailout procedures for the treatment of life-threatening hypertensive conditions that are refractory to drug treatment have mainly comprised the interventional denervation of renal arteries. The utilization of BAT is new in this emergency context and showed a significant, immediate, and sustained reduction of blood pressure

  6. Pulmonary artery segmentation and quantification in sickle cell associated pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Linguraru, Marius George; Mukherjee, Nisha; Van Uitert, Robert L.; Summers, Ronald M.; Gladwin, Mark T.; Machado, Roberto F.; Wood, Bradford J.

    2008-03-01

    Pulmonary arterial hypertension is a known complication associated with sickle-cell disease; roughly 75% of sickle cell disease-afflicted patients have pulmonary arterial hypertension at the time of death. This prospective study investigates the potential of image analysis to act as a surrogate for presence and extent of disease, and whether the size change of the pulmonary arteries of sickle cell patients could be linked to sickle-cell associated pulmonary hypertension. Pulmonary CT-Angiography scans from sickle-cell patients were obtained and retrospectively analyzed. Randomly selected pulmonary CT-Angiography studies from patients without sickle-cell anemia were used as negative controls. First, images were smoothed using anisotropic diffusion. Then, a combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries. From the centerline, the diameters at the pulmonary trunk and first branch of the pulmonary arteries were measured automatically. Arterial diameters were normalized to the width of the thoracic cavity, patient weight and body surface. Results show that the pulmonary trunk and first right and left pulmonary arterial branches at the pulmonary trunk junction are significantly larger in diameter with increased blood flow in sickle-cell anemia patients as compared to controls (p values of 0.0278 for trunk and 0.0007 for branches). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.

  7. Natriuretic peptide resistance of mesenteric arteries in spontaneous hypertensive rat is alleviated by exercise.

    PubMed

    Yu, J; Zhang, B; Su, X-L; Tie, R; Chang, P; Zhang, X-C; Wang, J-B; Zhao, G; Zhu, M-Z; Zhang, H-F; Chen, B-Y

    2016-06-20

    Proximal resistance vessels, such as the mesenteric arteries, contribute substantially to the peripheral resistance. The reactivity of resistance vessels to vasoactive substance like natriuretic peptides plays an important role in the regulation of blood pressure. In current study, we investigated the reactivity of mesenteric arteries to atrial natriuretic peptide (ANP), a well known vasodilating factor, in spontaneously hypertensive rats (SHR), as well as the effects of exercise training on it. As a result, ANP-induced vasorelaxation was attenuated in SHR with significantly increased phosphodiesterase type 5 (PDE5), and decreased cGMP/ANP ratio, compared with WKY rats as control. Intriguingly, the decreased reactivity to ANP in SHR was markedly reversed by exercise training. In addition, ANP resistance of in vitro mesenteric arteries was diminished by sildenafil a potent selective inhibitor of PDE5. In conclusion, ANP resistance occurs in resistance vessels of SHR, suggesting predisposition to hypertension, which can be reversed by exercise. PMID:26447511

  8. The Effects and Mechanism of Atorvastatin on Pulmonary Hypertension Due to Left Heart Disease

    PubMed Central

    Wang, Qing; Guo, Yi-Zhan; Zhang, Yi-Tao; Xue, Jiao-Jie; Chen, Zhi-Chong; Cheng, Shi-Yao; Ou, Mao-De; Cheng, Kang-Lin; Zeng, Wei-Jie

    2016-01-01

    Background Pulmonary hypertension due to left heart disease (PH-LHD) is one of the most common forms of PH, termed group 2 PH. Atorvastatin exerts beneficial effects on the structural remodeling of the lung in ischemic heart failure. However, few studies have investigated the effects of atorvastatin on PH due to left heart failure induced by overload. Methods Group 2 PH was induced in animals by aortic banding. Rats (n = 20) were randomly divided into four groups: a control group (C), an aortic banding group (AOB63), an atorvastatin prevention group (AOB63/ATOR63) and an atorvastatin reversal group (AOB63/ATOR50-63). Atorvastatin was administered for 63 days after banding to the rats in the AOB63/ATOR63 group and from days 50 to 63 to the rats in the AOB63/ATOR50-63 group. Results Compared with the controls, significant increases in the mean pulmonary arterial pressure, pulmonary arteriolar medial thickening, biventricular cardiac hypertrophy, wet and dry weights of the right middle lung, percentage of PCNA-positive vascular smooth muscle cells, inflammatory infiltration and expression of RhoA and Rho-kinase II were observed in the AOB63 group, and these changes concomitant with significant decreases in the percentage of TUNEL-positive vascular smooth muscle cells. Treatment of the rats in the AOB63/ATOR63 group with atorvastatin at a dose of 10 mg/kg/day significantly decreased the mean pulmonary arterial pressure, right ventricular hypertrophy, pulmonary arteriolar medial thickness, inflammatory infiltration, percentage of PCNA-positive cells and pulmonary expression of RhoA and Rho-kinase II and significantly augmented the percentage of TUNEL-positive cells compared with the AOB63 group. However, only a trend of improvement in pulmonary vascular remodeling was detected in the AOB63/ATOR50-63 group. Conclusions Atorvastatin prevents pulmonary vascular remodeling in the PH-LHD model by down-regulating the expression of RhoA/Rho kinase, by inhibiting the

  9. Prevalence of coronary artery–pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension

    PubMed Central

    Blanchard, Daniel G.; Knowlton, Kirk U.; McDivit, Anna M.; Pretorius, Victor; Madani, Michael M.; Fedullo, Peter F.; Kerr, Kim M.; Kim, Nick H.; Poch, David S.; Auger, William R.; Daniels, Lori B.

    2015-01-01

    Abstract This study sought to determine the prevalence of coronary artery–pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery–pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery–pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery–pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery–pulmonary artery collateral among control subjects (0.4%; P < 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P < 0.001) or lobar arteries (P < 0.001). In conclusion, the prevalence of coronary artery–pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion. PMID:26064456

  10. Alterations in structure of elastic laminae of rat pulmonary arteries in hypoxic hypertension.

    PubMed

    Liu, S Q

    1996-11-01

    The effect of hypoxic hypertension on the remodeling process of the elastic laminae of the rat hilar pulmonary arteries (PAs) was studied by electron microscopy. Rats were exposed to hypoxia (10% O2) for periods of 0.5, 2,6,12,48,96,144, and 240 h. Changes in the structure of the PA elastic laminae were examined and analyzed with respect to changes in the PA wall tensile stress. The PA blood pressure increased rapidly within the first several hours of hypoxia and reached a stable level within 2 days, whereas the PA wall tensile stress increased initially due to elevated blood pressure and then decreased after 48 h due to vessel wall thickening and returned to the control level after 4 days. In association with these changes, the elastic laminae, which appeared homogeneous in normal control rats, changed into structures composed of randomly oriented filaments and edematous contents with an increase in the volume during the early period of hypoxia and regained their homogeneous appearance and normal volume after 4 days. The changes in the elastic laminae were correlated with changes in the tensile stress. These changes were associated with a transient decrease in the stiffness of the PAs. In hypoxic rats given nifedipine, no change was found in the blood pressure, the tensile stress, or the structure of the elastic laminae of the PAs despite continuous exposure to hypoxia. These results suggested that altered tensile stress in the PA wall played a critical role in the initiation and regulation of structural changes in the elastic laminae and that these changes might contribute to alterations in the mechanical properties of the PA in hypoxic hypertension. PMID:8941540

  11. Systemic antioxidant properties of L-carnitine in two different models of arterial hypertension.

    PubMed

    Mate, Alfonso; Miguel-Carrasco, José L; Monserrat, María T; Vázquez, Carmen M

    2010-06-01

    In spite of a wide range of drugs being available in the market, treatment of arterial hypertension still remains a challenge, and new therapeutic strategies could be developed in order to improve the rate of success in controlling this disease. Since oxidative stress has gained importance in the last few years as one of the mechanisms involved in the origin and development of hypertension, and considering that L-carnitine (LC) is a useful compound in different pathologies characterized by increased oxidative status, the aim of the present study was to investigate the systemic antioxidant effect of LC and its correlation to blood pressure in two experimental models of hypertension: (1) spontaneously hypertensive rats (SHR) and (2) rats with hypertension induced by N(omega)-nitro-L-arginine methyl ester (L-NAME). Treatment with captopril was also performed in SHR in order to compare the antioxidant and antihypertensive effects of LC and captopril. The antioxidant defense capacity, in terms of antioxidant enzyme activity, glutathione system availability and plasma total antioxidant capacity, was measured in both animal models with or without an oral, chronic treatment with LC. All the antioxidant parameters studied were diminished in SHR and in L-NAME-treated animals, an alteration that was in general reversed after treatments with LC and captopril. In addition, LC produced a significant but not complete reduction of systolic and diastolic blood pressure levels in these two models of hypertension, whereas captopril was able to normalize blood pressure. Both LC and captopril prevented the reduction in nitric oxide (NO) levels observed in hypertensive animals. This suggests a decrease in the systemic oxidative stress and a higher availability of NO induced by LC in a similar way to captopril's effects, which could be relevant in the management of arterial hypertension eventually. PMID:20506010

  12. Newly diagnosed hyperthyroidism in the 25th gestational week of pregnancy presenting with systolic arterial hypertension only.

    PubMed

    Zaveljcina, Janez; Legan, Mateja; Gaberšček, Simona

    2016-05-01

    We present a case of a 30-year-old woman diagnosed with arterial hypertension in the 25th week of pregnancy. Our search for secondary causes of arterial hypertension revealed hyperthyroid Hashimoto's thyroiditis (HT), which was treated with propilthiouracil. Three weeks after delivery, she was normotensive without medication. In the next four months, she developed hypothyroidism and treatment with L-thyroxine was started. In conclusion, in the second half of pregnancy, a hyperthyroid HT can occur - in spite of the well-known amelioration of autoimmune thyroid disorders in that period, and can be the only cause of arterial hypertension. PMID:26979941

  13. Reduced activity of SKC a and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats.

    PubMed

    Kong, Billy W C; Man, Ricky Y K; Gao, Yuansheng; Vanhoutte, Paul M; Leung, Susan W S

    2015-06-01

    Aging is accompanied by endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) and/or reduced endothelium-dependent hyperpolarizations (EDH). This study examines the hypothesis that hypertension aggravates the impairment of EDH-type relaxation due to aging. EDH-type relaxations were studied in superior mesenteric arteries isolated from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats of 12, 36, 60, and 72 weeks of age. EDH-type relaxations in WKY were reduced with aging, and this was associated with an impairment of the function of small-conductance calcium-activated potassium channels (SKC a) and sodium-potassium ATPase (Na-K ATPase). EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging. Pharmacological experiments suggested a reduced involvement of SKC a and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR. These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension. The latter exacerbation appears to involve proteins associated with the process of cellular senescence and is related to impaired function of SKC a and Na-K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats. PMID:26171229

  14. [Non-pharmacologic treatment of arterial hypertension in hemodialysis patients].

    PubMed

    Chazot, C; Charra, B

    2007-10-01

    High blood pressure in dialysis patients is related to extracellular volume excess and the related increase of systemic vascular resistances. Scribner has early described the treatment of hypertension with ultrafiltration and low salt diet, without any drugs. The dry weight method relies on the progressive reduction of the postdialysis body weight until blood pressure is normalized. Additional measures are needed such as low salt diet, neutral sodium balance during dialysis treatment, stop of antihypertensive drugs, adequate length of the dialysis session, and patient education. It may exist a lag time between the normalization of the extracellular volume and blood pressure. It is related to the correction of the hemodynamic consequences of the extracellular volume overload. Moreover, the dry weight may potentially vary in patients undergoing catabolic intercurrent events. The complications of these changes (severe hypertension, pulmonary oedema) must be anticipated by the nephrologist and the staff to avoid additional morbidity to the patient. PMID:18340684

  15. Variability of arterial blood pressure in normal and hypertensive pregnancy.

    PubMed

    Oney, T; Meyer-Sabellek, W

    1990-12-01

    In normal pregnancy the circadian blood pressure rhythm is similar to that in the non-pregnant state, with the highest blood pressure values in the morning and the lowest at midnight. This rhythm is lost in patients with pre-eclampsia. Women with severe pre-eclampsia show a reversed circadian rhythm, with a nocturnal increase in blood pressure during the sleeping phase. Although the reasons for this nocturnal hypertension in severe pre-eclampsia are poorly understood, the results suggest that pre-eclamptic women are endangered by hypertensive emergencies, mostly at night. Therefore blood pressure measurement should be extended to the night, and antihypertensive treatment must be adapted to the demands of a reversed circadian rhythm in relevant subgroups of patients. PMID:2082002

  16. Fat utilization and arterial hypertension in overweight/obese subjects

    PubMed Central

    2013-01-01

    Background The Respiratory Quotient is a parameter reflecting the utilization of the nutrients by a subject. It is associated with an high rate of subsequent weight gain and with the atherosclerosis. Subjects tending to burn less fat have an increased Respiratory Quotient. Aim of this study was to investigate on the relationship between the Respiratory Quotient and the cardiovascular risk factors. Methods In this cross-sectional study we enrolled 223 individuals of both sexes aged 45–75 ys that were weight stable, receiving a balanced diet, and not affected by debilitating disease or cardiovascular disease. The Respiratory Quotient was measured by Indirect Calorimetry. The measurement of the Blood Pressure was obtained by a mercury sphygmomanometer. Results We enrolled 133 female and 90 male. Systolic blood pressure only was positively correlated to the Respiratory Quotient in univariate and multivariate regression analysis (p=0,017). The prevalence of hypertension was significatively different between the quartiles of the Respiratory Quotient, with the highest prevalence in the IV quartile (p=0,024). Conclusion High value of the Respiratory Quotient, an index of nutrients utilization, is associated to an high prevalence of Hypertension. It is possible that in the subjects with high Respiratory Quotient and high body mass index, the activation of the renin angiotensin system, in concert to the reduction of the utilization of the endogenous fat stores, could increase the risk of hypertension. PMID:23815947

  17. From arterial hypertension complications to von Hippel-Lindau syndrome diagnosis.

    PubMed

    Kozaczuk, Sylwia; Ben-Skowronek, Iwona

    2015-01-01

    Von Hippel-Lindau syndrome is a rare, genetically based, autosomal dominant disorder. Its course is accompanied by the development of multiple neoplasms with the following tumours diagnosed most commonly in the central nervous system haemangioblastoma, clear cell renal cell carcinoma, phaeochromocytomas, pancreatic islet tumours, and endolymphatic sac tumours. Additionally, renal and pancreatic cystadenomas and epididymal cystadenomas have been diagnosed in males and cystadenomas of the broad ligament of the uterus have been diagnosed in females.The following paper presents the diagnostic way in a boy with vision disorders as the first symptom. Hypertension retinopathy and extremely elevated blood pressure were observed during ophthalmologic consultation. Complications of arterial hypertension were confirmed by echocardiography, which diagnosed hypertension cardiomyopathy. Hypertension retinopathy was confirmed by optical coherence tomography. Examinations performed in the neurology, cardiology, and finally endocrinology indicated a bilateral phaeochromocytoma as the cause of arterial hypertension. Moreover, some genetic investigations showed a mutation in the VHL ex.1 p.Y112 C gene responsible for the hereditary form of phaeochromocytoma which confirmed von Hippel-Lindau syndrome. After surgical treatment of phaeochromocytoma the patient needed careful management according to the surveillance protocol for von Hippel-Lindau disease. PMID:26268347

  18. Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers.

    PubMed

    Yang, Y; Zhang, B K; Liu, D; Nie, W; Yuan, J M; Wang, Z; Guo, Y M

    2012-01-01

    1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-β-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers. PMID:23281754

  19. Subclinical arterial and cardiac damage in white-coat and masked hypertension.

    PubMed

    Wojciechowska, Wiktoria; Stolarz-Skrzypek, Katarzyna; Olszanecka, Agnieszka; Klima, Łukasz; Gąsowski, Jerzy; Grodzicki, Tomasz; Kawecka-Jaszcz, Kalina; Czarnecka, Danuta

    2016-08-01

    The study aimed to compare arterial and echocardiographic parameters in subjects with newly diagnosed masked (MH) or white-coat hypertension (WCH) to subjects with sustained normotension or sustained hypertension, defined according to the 2014 European Society of Hypertension practice guidelines for ambulatory blood pressure (BP) monitoring. We recruited 303 participants (mean age 46.9 years) in a family-based population study. SpaceLabs monitors and oscillometric sphygmomanometers were used to evaluate ambulatory and office BP, respectively. Central pulse pressure (PP) and aortic pulse-wave velocity (PWV) were measured with pulse-wave analysis (SphygmoCor software). Carotid intima-media thickness (IMT) and cardiac evaluation were assessed by ultrasonography. Analysing participants without antihypertensive treatment (115 sustained normotensives, 41 sustained hypertensives, 20 with WCH, 25 with MH), we detected significantly higher peripheral and central PP, PWV, IMT and left ventricular mass index in hypertensive subgroups than in those with sustained normotension. The differences between categories remained significant for peripheral PP and PWV after adjustment for confounding factors, including 24 h systolic and diastolic BP. Participants with WCH and MH, defined according to strict criteria, had more pronounced arterial and heart involvement than normotensive participants. The study demonstrates a high prevalence of these conditions in the general population that deserves special attention from physicians. PMID:26953075

  20. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension.

    PubMed

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A; Castillo, Andrés E; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E; Kalergis, Alexis M

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  1. Role of the Renin-Angiotensin-Aldosterone System beyond Blood Pressure Regulation: Molecular and Cellular Mechanisms Involved in End-Organ Damage during Arterial Hypertension

    PubMed Central

    Muñoz-Durango, Natalia; Fuentes, Cristóbal A.; Castillo, Andrés E.; González-Gómez, Luis Martín; Vecchiola, Andrea; Fardella, Carlos E.; Kalergis, Alexis M.

    2016-01-01

    Arterial hypertension is a common condition worldwide and an important predictor of several complicated diseases. Arterial hypertension can be triggered by many factors, including physiological, genetic, and lifestyle causes. Specifically, molecules of the renin-angiotensin-aldosterone system not only play important roles in the control of blood pressure, but they are also associated with the genesis of arterial hypertension, thus constituting a need for pharmacological interventions. Chronic high pressure generates mechanical damage along the vascular system, heart, and kidneys, which are the principal organs affected in this condition. In addition to mechanical stress, hypertension-induced oxidative stress, chronic inflammation, and the activation of reparative mechanisms lead to end-organ damage, mainly due to fibrosis. Clinical trials have demonstrated that renin-angiotensin-aldosterone system intervention in hypertensive patients lowers morbidity/mortality and inflammatory marker levels as compared to placebo patients, evidencing that this system controls more than blood pressure. This review emphasizes the detrimental effects that a renin-angiotensin-aldosterone system (RAAS) imbalance has on health considerations above and beyond high blood pressure, such as fibrotic end-organ damage. PMID:27347925

  2. Hypertension.

    PubMed

    Oparil, S; Calhoun, D A

    1989-03-01

    An estimated 58 million Americans are at increased risk of morbidity and premature death due to high blood pressure (BP) and require some type of therapy or systematic monitoring. This article focuses on recent advances in our understanding of the pathogenesis of hypertension, new approaches to the diagnosis and treatment of secondary hypertension, and current views of the most appropriate nonpharmacologic and pharmacologic therapy for essential hypertension. In view of the extremely high prevalence of the disorder, emphasis is placed on efficient and cost-effective strategies for diagnosing and managing the hypertensive patient. Recent evidence indicates that nonpharmacologic therapy, including dietary potassium and calcium supplements, reduction of salt intake, weight loss for the obese patient, regular exercise, a diet high in fiber and low in cholesterol and saturated fats, smoking cessation, and moderation of alcohol consumption produces significant sustained reductions in BP while reducing overall cardiovascular risk. Accordingly, nonpharmacologic antihypertensive therapy should be included in the treatment of all hypertensive patients. In persons with mild hypertension, nonpharmacologic approaches may adequately reduce BP, thereby avoiding the expense and potential side effects of drug therapy. In patients with more severe hypertension, nonpharmacologic therapy, used in conjunction with pharmacologic therapy, can reduce the dosage of antihypertensive medications necessary for BP control. Patients treated with nonpharmacologic therapy only should be followed closely, and if BP control is not satisfactory, drug therapy should be added. The large number of drugs available for use in hypertension treatment, coupled with our rapidly expanding knowledge of the pathophysiology of hypertension and of the adverse effects of these drugs in individual patient groups, make it possible to individualize antihypertensive treatment. When used as monotherapy, most agents

  3. Pulmonary Arterial Hypertension Associated with Congenital Portosystemic Shunts Treated with Transcatheter Embolization and Pulmonary Vasodilators.

    PubMed

    Sato, Haruka; Miura, Masanobu; Yaoita, Nobuhiro; Yamamoto, Saori; Tatebe, Shunsuke; Aoki, Tatsuo; Satoh, Kimio; Ota, Hideki; Takase, Kei; Sugimura, Koichiro; Shimokawa, Hiroaki

    2016-01-01

    Cardiopulmonary abnormalities are often present in patients with liver diseases. We herein report a case of congenital portosystemic shunts complicated by hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH). A 57-year-old woman complained of dyspnea and was subsequently diagnosed with HPS and PoPH caused by congenital portosystemic shunts. Although shunt closure by transcatheter embolization was successfully performed, her dyspnea worsened and pulmonary artery pressure and pulmonary vascular resistance elevated. Conventional vasodilator therapy was started, resulting in an improvement of pulmonary hypertension (PH). In some patients with congenital portosystemic shunts, shunt closure could exacerbate PH, and vasodilator therapy may be effective. PMID:27580545

  4. Hypertension and cerebral vasoreactivity: a continuous arterial spin labeling magnetic resonance imaging study.

    PubMed

    Hajjar, Ihab; Zhao, Peng; Alsop, David; Novak, Vera

    2010-11-01

    Hypertension is associated with microvascular and macrovascular brain injury but its direct influence on the cerebral circulation is not fully clear. Our objective was to investigate the association of hypertension with global and regional cerebral vasoreactivity to CO(2) using continuous arterial spin labeling MRI, independent of stroke and white matter hyperintensities. Participants (n=62; mean age: 66.7±1.0 years, 55% women, 84% white, 65% hypertension, 47% stroke) underwent arterial spin labeling perfusion MRI during normal breathing, 5% CO(2) rebreathing, and hyperventilation, as well as 24-hour ambulatory blood pressure monitoring. Vasoreactivity was the slope of the regression between cerebral perfusion and end-tidal CO(2). White matter hyperintensity volumes were quantified. Nighttime dipping was calculated as the percentage decline in nighttime/daytime blood pressure. After accounting for stroke and white matter hyperintensity volume, hypertensive participants had lower global vasoreactivity (1.11±0.13 versus 0.43±0.1 mL/100 g per minute per millimeter of mercury; P=0.0012). Regionally, this was significant in the frontal, temporal, and parietal lobes. Higher mean systolic blood pressure was associated with lower vasoreactivity (decreased by 0.11 U/10-mm Hg increase in systolic blood pressure; P=0.04), but nighttime dipping was not (P=0.2). The magnitude of decrease in vasoreactivity in hypertension without stroke was comparable to the magnitude of decrease in vasoreactivity in stroke without hypertension. Hypertension has a direct negative effect on the cerebrovascular circulation independent of white matter hyperintensities and stroke that is comparable to that seen with stroke. Because lower vasoreactivity is associated with poor outcomes, studies of the impact of antihypertensive on vasoreactivity are important. PMID:20876450

  5. [Relationship between left ventricular mass and prognosis of arterial hypertension].

    PubMed

    Devereux, R B

    1990-12-01

    Echocardiographic measurement of left ventricular mass has provided a way of evaluating the undesirable effects of high blood pressure on the heart in the same way as for obesity, excess salt intake and blood hyperviscosity. Recently, the left ventricular mass was shown to correlate (r = 0.81) with the hemodynamic stimuli of blood pressure, stroke volume and left ventricular contractility. Prospective trials at Cornell and Framingham indicate that left ventricular mass is a powerful predictive factor of the risk of complications in hypertension. In the first of these trials, we demonstrated in a 5 year follow-up study of 140 men with uncomplicated hypertension that the incidence of death, myocardial infarction or angina requiring myocardial revascularisation, was four times greater in patients with increased left ventricular mass and that this association was independent of the blood pressure levels. Then, in a 10 year follow-up study of hypertensive patients of both sexes, we established that the left ventricular mass was the most powerful predictive factor of mortality and morbidity and that this was so marked (15% death rate in subjects with LVH vs 1% in subjects with normal left ventricular mass--p less than 0.00001--, cardiovascular accidents in 26% of subjects with LVH compared with 12% in subjects with normal left ventricular mass--p less than 0.0001) that only left ventricular mass and age were independant predictive factors of morbid events in multiple variable analysis. In the Framingham study, the frequency of coronary events in a 4 year follow-up period of healthy subjects from the original cohort (average age 69 years) was significantly related to the left ventricular mass and independent of other risk factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2080892

  6. [Pathophysiology of left ventricular hypertrophy in arterial hypertension].

    PubMed

    Vallotton, M B; Braconi-Quintaje, S; Lang, U

    1997-02-11

    The role of left ventricular hypertrophy as an independent risk factor for subsequent cardio-vascular events is well established, therefore the authors, in this brief review, describe the endocrine function of the heart and the role played by various factors, including hormones, in the development of cardiac remodeling during the course of hypertension. They then outline the present state of our knowledge concerning transmembrane signaling in the cardiomyocyte in response to an activation of specific receptors for vasoactive hormones of the renin-angiotensin II-aldosterone system. PMID:9139339

  7. Epidural Anesthesia for Cesarean Delivery in a Patient With Severe Pulmonary Artery Hypertension and a Right-to-Left Shunt.

    PubMed

    Krenz, Elizabeth I; Hart, Stuart R; Russo, Melissa; Alkadri, Mohi

    2011-01-01

    A 38-year-old woman with severe pulmonary artery hypertension and a right-to-left shunt of unknown etiology presented at 32 weeks' gestational age. Determination of the cause of her pulmonary hypertension by transesophageal echocardiography was delayed until after delivery secondary to anesthetic risk. She was successfully anesthetized for cesarean delivery using epidural anesthesia. Systemic vascular resistance was maintained using phenylephrine hydrochloride before delivery and vasopressin after delivery. Transesophageal echocardiography after delivery revealed a patent foramen ovale, indicating a diagnosis of idiopathic pulmonary artery hypertension and a very poor prognosis. Differentiating between Eisenmenger syndrome and idiopathic pulmonary artery hypertension may not be important for determining the optimal anesthetic management of patients with pulmonary hypertension but is important in assessing long-term prognosis. PMID:21603339

  8. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Medical and surgical management for pulmonary arterial hypertension

    PubMed Central

    Idrees, Majdy M.; Swiston, John; Nizami, Imran; Al Dalaan, Abdullah; Levy, Robert D.

    2014-01-01

    Prior to the availability of the pulmonary arterial hypertension (PAH)-specific therapy, PAH was a dreadful disease with a very poor prognosis. Better understanding of the complex pathobiology of PAH has led to a major therapeutic evolution. International regulatory agencies have approved many specific drugs with different pharmacologic pathways and routes of administration. In the year 2013, two new drugs with great potentials in managing PAH have been added to the treatment options, macitentan and riociguat. Additional drugs are expected to come in the near future. A substantial body of evidence has confirmed the effectiveness of pulmonary arterial hypertension (PAH)-specific therapies in improving the patients’ symptomatic status and slowing down the rate of clinical deterioration. Although the newer modern medications have significantly improved the survival of patients with PAH, it remains a non-curable and fatal disease. Lung transplantation (LT) remains the only therapeutic option for selected patients with advanced disease who continue to deteriorate despite optimal therapy. PMID:25077002

  9. [The influence of citoflavin on molecular mechanisms of hypertensive encephalopathy development in patients with systolic arterial hypertension].

    PubMed

    Kartashova, E A; Romantsov, M G; Sarvilina, I V

    2014-01-01

    The molecular pharmacological effects of cytoflavin in patients with hypertensive encephalopathy (HE) and isolated systolic arterial hypertension (ISAH) have been investigated using the following methods: assessment of complaints, 24-hour arterial pressure monitoring, ultrasound diagnostics including echocardiography, measurement of lipid profiles and coagulograms, and molecular phenotyping by MALDI-TOF/TOF-MS. A combination of cytoflavin administration with standard therapy of HE and ISAH led to the most expressed return development of clinical symptoms, restoration of the hemodynamic, structural, and geometrical parameters of cardiovascular system, and normalization of the indices of lipid profiles and coagulograms in comparison to patients with HE and ISAH, which accepted only standard therapy. Molecular mechanisms of cytoflavin action have been revealed, which include control of the activity of cellular signaling pathways by means of intermolecular interactions. The optimized therapy of HE and ISAH is recommended for clinical application, which assumes a combined use of standard therapy and cytoflavin and provides a geroprotective action upon the cardiovascular system. PMID:25102730

  10. Effects of bosentan on peripheral endothelial function in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension

    PubMed Central

    Adachi, Shiro; Nakano, Yoshihisa; Kamimura, Yoshihiro; Shimokata, Shigetake; Takeshita, Kyosuke; Murohara, Toyoaki; Kondo, Takahisa

    2016-01-01

    Abstract Endothelin receptor antagonists (ERAs) have been shown to improve the prognosis of patients with pulmonary arterial hypertension (PAH). However, the effect of the oral dual ERA bosentan on peripheral endothelial dysfunction (PED), as assessed by flow-mediated vasodilation (FMD), in patients with pulmonary hypertension is not well characterized. We investigated the effect of bosentan on PED in patients with PAH or inoperable chronic thromboembolic pulmonary hypertension (CTEPH). A total of 18 patients with PAH and 8 with CTEPH were treated with bosentan. All patients underwent FMD assessment before and after 3 months of bosentan treatment. Whereas FMD increased from 6.01% ± 2.42% at baseline to 8.07% ± 3.18% after 3 months (P < 0.0001) in patients with PAH, those with CTEPH showed no change in FMD after bosentan therapy. In addition, FMD at baseline showed no correlation with pulmonary vascular resistance (r = 0.09) or plasma brain natriuretic peptide levels (r = −0.23) in patients with PAH. Bosentan treatment ameliorated PED in patients with PAH but not in those with inoperable CTEPH. In addition, FMD did not correlate with PAH severity. PMID:27252842

  11. Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis

    PubMed Central

    Papaioannou, Andriana I; Zakynthinos, Epaminondas; Kostikas, Konstantinos; Kiropoulos, Theodoros; Koutsokera, Angela; Ziogas, Athanasios; Koutroumpas, Athanasios; Sakkas, Lazaros; Gourgoulianis, Konstantinos I; Daniil, Zoe D

    2009-01-01

    Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis. PMID:19426547

  12. Management of the patient with pulmonary arterial hypertension receiving intravenous prostacyclin: an expert nurse practical guide.

    PubMed

    Kingman, Martha S; Lombardi, Sandra

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a severely disabling disorder characterized by elevated pulmonary artery pressure ultimately leading to right heart failure and death. Treatment options have significantly increased over the past decade. Intravenous prostacyclins remain the treatment of choice for advanced PAH, leading to long-term clinical benefits and improved survival. Their administration requires a high level of nursing competency and presents considerable challenges for patients and caregivers. This article reviews the characteristics of currently available intravenous prostacyclins and provides a practical guide for nurses who may have had limited exposure to intravenous prostacyclins and their unique dosing, side effects, and titration characteristics. PMID:25376321

  13. Remodeling of conduit arteries in hypertension and flow-overload obeys a minimum energy principle

    PubMed Central

    Zhang, Wei; Kassab, Ghassan S.

    2009-01-01

    Arterial remodeling is an important process in physiology and pathophysiology. Based on an energy minimization method, Murray’s law predicts the optimal inner radius. Application of Darcy’s law in the wall results in an optimal outer radius. The average wall stress is computed by the Laplace’s law. Using these formulas, a large porcine coronary artery in hypertension is studied. The results reveal how wall thickness and average circumferential stress change after increasing blood pressure and volume flow rate. The theoretical predictions are in good qualitative agreement with experimental observations. The advantage and limitation of the current approach are discussed. PMID:18606418

  14. Prevalence of systemic arterial hypertension, electrocardiogram abnormalities, and noise-induced hearing loss in agricultural workers.

    PubMed

    Tomei, Gianfranco; Sancini, Angela; Tomei, Francesco; Vitarelli, Antonio; Andreozzi, Giorgia; Rinaldi, Giovanni; Di Giorgio, Valeria; Samperi, Ilaria; Fiaschetti, Maria; Tasciotti, Zaira; Cetica, Carlotta; Capozzella, Assunta; Ciarrocca, Manuela; Caciari, Tiziana

    2013-01-01

    ABSTRACT The literature suggests that farmers nowadays are more likely to contract cardiovascular diseases than in the past. This study involved 79 farmers and 64 controls. The workers completed a questionnaire to identify exclusion factors for audiological and cardiovascular risk factors. The participants underwent medical examination, measurement of blood pressure, electrocardiogram, blood tests, audiometry, and measurement of noise exposure. The farmers were found to have a higher prevalence of systolic and diastolic arterial hypertension as well as electrocardiogram (ECG) abnormalities compared with the controls. A significant prevalence of arterial hypertension was detected in the farmers exposed to noise, when compared with those who were not exposed. These results suggest that farmers are at risk of cardiovascular effects and that noise is a cardiovascular risk factor for farmers. PMID:23697692

  15. Role of vasopressin and aldosterone in pulmonary arterial hypertension: A pilot study

    PubMed Central

    Bansal, Shweta; Badesch, David; Bull, Todd; Schrier, Robert W.

    2009-01-01

    Much has been learned about the pathophysiological state that underlies the development of increased total body volume and edema in left ventricular failure. Very little, however, is known about the mechanism underlying systemic hypervolemia in patients with isolated right ventricular dysfunction. In this manuscript, we describe our randomized clinical trial to assess the relationship between severity of pulmonary arterial hypertension and neurohormonal activation, total plasma volume and renal function. We assess the role of aldosterone and vasopressin in volume retention in patients with pulmonary arterial hypertension with right ventricular failure. As understanding of the pathogenesis of left ventricular failure has been associated with improved therapies, the better understanding of the mechanisms of isolated right ventricular cardiac failure will also lead to improved patient care. PMID:19375522

  16. Modeled PFOA Exposure and Coronary Artery Disease, Hypertension, and High Cholesterol in Community and Worker Cohorts

    PubMed Central

    Steenland, Kyle

    2014-01-01

    Background: Several previous studies, mostly cross-sectional, have found associations between perfluorooctanoic acid (PFOA) and high cholesterol levels, but studies of hypertension and heart disease have had inconsistent findings. Objectives: In this study we examined the association between modeled PFOA exposure and incident hypertension, hypercholesterolemia, and coronary artery disease among workers at a Mid-Ohio Valley chemical plant that used PFOA, and residents of the surrounding community. Methods: Community- and worker-cohort participants completed surveys during 2008–2011 covering demographics, health-related behaviors, and medical history. Cox proportional hazard models, stratified by birth year, modeled the hazard of each outcome (starting at 20 years of age) as a function of retrospective serum PFOA concentration estimates (generated through fate, transport and exposure modeling), controlling for sex, race, education, smoking, alcohol use, body mass index, and diabetes. Results: Among 32,254 participants (28,541 community; 3,713 worker), 12,325 reported hypertension with medication, 9,909 reported hypercholesterolemia with medication, and 3,147 reported coronary artery disease (2,550 validated). Hypercholesterolemia incidence increased with increasing cumulative PFOA exposure (sum of yearly serum concentration estimates), most notably among males 40–60 years of age. Compared with the lowest exposure quintile (< 142 ng/mL-years), hazard ratios for subsequent quintiles (ng/mL-years: 142 to < 234; 234 to < 630; 630 to < 3,579; ≥ 3,579) were 1.24, 1.17, 1.19, and 1.19 overall and 1.38, 1.32, 1.31, and 1.44 among men 40–60 years of age. There was no apparent association between PFOA exposure and hypertension or coronary artery disease incidence. Conclusions: Higher PFOA exposure was associated with incident hypercholesterolemia with medication, but not with hypertension or coronary artery disease. Citation: Winquist A, Steenland K. 2014. Modeled PFOA

  17. [Effects of surgical treatment on circadian variations of arterial pressure in patients with primary aldosteronism and renovascular hypertension].

    PubMed

    Kosmacheva, E D; Minkin, S E; Chikhladze, N M; Arabidze, G G; At'kov, O Iu

    1990-05-01

    Noninvasive recording of blood pressure (BP) with a portable Del Mar Avionics monitor (USA) revealed its abnormal circadian rhythm in patients with renovascular hypertension or arterial hypertension caused by adrenal aldosteroma. Surgical treatment was shown to result in a significant decrease in blood pressures and normalization of its circadian rhythm in the early postoperative period. PMID:2391803

  18. Analysis of arterial wall remodeling in hypertension based on lamellar modeling.

    PubMed

    Taghizadeh, Hadi; Tafazzoli-Shadpour, Mohammad; Shadmehr, Mohammad B

    2015-09-01

    Arterial wall remodels its geometry and mechanical properties in response to hypertension to maintain functionality. The elevated pressure is sensed through cellular mechanotransduction pathways, and extra extracellular matrix is synthesized, leading to thickening and stiffening. The present study enquires the response of aortic lamellar structure to hypertensive blood pressure regarding unchanged circumferential stress "profile" across the media as remodeling criterion. We tested the hypothesis that alterations in the thickness of structural layers contributes to maintain stress profile with least deviation from normotensive conditions. To test this notion, finite element analysis was recruited to evaluate stress profile, considering wall residual stress, and lamellar structure was adjusted through an optimization algorithm. Our results indicated 47% increased thickness of the aortic media that originates from nonhomogenous thickening of the microstructural units. The thickening and stiffening responses of the wall tissue were coupled, and the optimized pattern of hypertension-induced remodeling was established. PMID:26369443

  19. Morning blood pressure surge is associated with arterial stiffness and sympathetic baroreflex sensitivity in hypertensive seniors

    PubMed Central

    Okada, Yoshiyuki; Galbreath, M. Melyn; Shibata, Shigeki; Jarvis, Sara S.; Bivens, Tiffany B.; Vongpatanasin, Wanpen; Levine, Benjamin D.

    2013-01-01

    Morning blood pressure (BP) surge is considered to be an independent risk factor for cardiovascular diseases. We tested the hypothesis that increased large-artery stiffness and impaired sympathetic baroreflex sensitivity (BRS) contribute to augmented morning surge in elderly hypertensive subjects. Morning surge was assessed as morning systolic BP averaged for 2 h just after waking up minus minimal sleeping systolic BP by using ambulatory BP monitoring (ABPM) in 40 untreated hypertensive [68 ± 1 (SE) yr] and 30 normotensive (68 ± 1 yr) subjects. Beat-by-beat finger BP and muscle sympathetic nerve activity (MSNA) were recorded in the supine position and at 60° upright tilt. We assessed arterial stiffness with carotid-to-femoral pulse wave velocity (cfPWV) and sympathetic BRS during spontaneous breathing. Awake and asleep ABPM-BPs and morning surge were higher in hypertensive than normotensive subjects (all P < 0.001). cfPWV was higher (P = 0.002) and sympathetic BRS was lower (P = 0.096) in hypertensive than normotensive subjects. Hypertensive subjects with morning surge ≥35 mmHg (median value) had higher cfPWV (11.9 ± 0.5 vs. 9.9 ± 0.4 m/s, P = 0.002) and lower sympathetic BRS (supine: −2.71 ± 0.25 vs. −3.73 ± 0.29, P = 0.011; upright: −2.62 ± 0.22 vs. −3.51 ± 0.35 bursts·100 beats−1·mmHg−1, P = 0.052) than those with morning surge <35 mmHg. MSNA indices were similar between groups (all P > 0.05), while upright total peripheral resistance was higher in hypertensive subjects with greater morning surge than those with lesser morning surge (P = 0.050). Morning surge was correlated positively with cfPWV (r = 0.59, P < 0.001) and negatively with sympathetic BRS (r = 0.51, P < 0.001) in hypertensive subjects only. Thus, morning BP surge is associated with arterial stiffness and sympathetic BRS, as well as vasoreactivity during orthostasis in hypertensive seniors. PMID:23832695

  20. The adrenergic system in pulmonary arterial hypertension: bench to bedside (2013 Grover Conference series)

    PubMed Central

    Quaife, Robert A.

    2015-01-01

    Abstract In heart failure with reduced left ventricular ejection fraction (HFrEF), adrenergic activation is a key compensatory mechanism that is a major contributor to progressive ventricular remodeling and worsening of heart failure. Targeting the increased adrenergic activation with β-adrenergic receptor blocking agents has led to the development of arguably the single most effective drug therapy for HFrEF. The pressure-overloaded and ultimately remodeled/failing right ventricle (RV) in pulmonary arterial hypertension (PAH) is also adrenergically activated, which raises the issue of whether an antiadrenergic strategy could be effectively employed in this setting. Anecdotal experience suggests that it will be challenging to administer an antiadrenergic treatment such as a β-blocking agent to patients with established moderate-severe PAH. However, the same types of data and commentary were prevalent early in the development of β-blockade for HFrEF treatment. In addition, in HFrEF approaches have been developed for delivering β-blocker therapy to patients who have extremely advanced heart failure, and these general principles could be applied to RV failure in PAH. This review examines the role played by adrenergic activation in the RV faced with PAH, contrasts PAH-RV remodeling with left ventricle remodeling in settings of sustained increases in afterload, and suggests a possible approach for safely delivering an antiadrenergic treatment to patients with RV dysfunction due to moderate-severe PAH. PMID:26401244

  1. Clinical utility of treprostinil in the treatment of pulmonary arterial hypertension: an evidence-based review

    PubMed Central

    Buckley, Mitchell S; Berry, Andrew J; Kazem, Nadine H; Patel, Shardool A; Librodo, Paul A

    2014-01-01

    Pulmonary arterial hypertension (PAH) remains a progressive disease without a cure, despite the development of several treatment options over the past several decades. Its management strategy consists of the endothelin receptor antagonists (ambrisentan, bosentan, macitentan), phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil), and prostacyclin analogs (epoprostenol, treprostinil, iloprost). Treprostinil, a stable prostacyclin analog, displays vasodilatory effects in the pulmonary vasculature, as well as antiplatelet aggregation properties. Clinical practice guidelines recommend oral endothelin receptor antagonist or phosphodiesterase inhibitor therapy in mild to moderate PAH. Epoprostenol is specifically suggested as first-line therapy in moderate to severe PAH patients (ie, World Health Organization/New York Heart Association functional class III–IV). However, treprostinil may be an alternative option in these severe PAH patients. The longer half-life and stability at room temperature with treprostinil may be associated with lower risk of pulmonary hemodynamic worsening as a result of abrupt infusion discontinuation and less frequent drug preparation. These characteristics make treprostinil an attractive alternative to continuous infusion of epoprostenol, due to convenience and patient safety. The purpose of this review is to evaluate the safety and efficacy of continuous infusion of treprostinil as well as the inhaled and oral routes of administration in PAH. PMID:25018685

  2. Clinical utility of treprostinil in the treatment of pulmonary arterial hypertension: an evidence-based review.

    PubMed

    Buckley, Mitchell S; Berry, Andrew J; Kazem, Nadine H; Patel, Shardool A; Librodo, Paul A

    2014-01-01

    Pulmonary arterial hypertension (PAH) remains a progressive disease without a cure, despite the development of several treatment options over the past several decades. Its management strategy consists of the endothelin receptor antagonists (ambrisentan, bosentan, macitentan), phosphodiesterase-5 inhibitors (sildenafil, tadalafil, vardenafil), and prostacyclin analogs (epoprostenol, treprostinil, iloprost). Treprostinil, a stable prostacyclin analog, displays vasodilatory effects in the pulmonary vasculature, as well as antiplatelet aggregation properties. Clinical practice guidelines recommend oral endothelin receptor antagonist or phosphodiesterase inhibitor therapy in mild to moderate PAH. Epoprostenol is specifically suggested as first-line therapy in moderate to severe PAH patients (ie, World Health Organization/New York Heart Association functional class III-IV). However, treprostinil may be an alternative option in these severe PAH patients. The longer half-life and stability at room temperature with treprostinil may be associated with lower risk of pulmonary hemodynamic worsening as a result of abrupt infusion discontinuation and less frequent drug preparation. These characteristics make treprostinil an attractive alternative to continuous infusion of epoprostenol, due to convenience and patient safety. The purpose of this review is to evaluate the safety and efficacy of continuous infusion of treprostinil as well as the inhaled and oral routes of administration in PAH. PMID:25018685

  3. New Biochemical Insights into the Mechanisms of Pulmonary Arterial Hypertension in Humans

    PubMed Central

    Blanco, Isabel; Izquierdo-García, José Luis; Dudzik, Danuta; Markuszewski, Michał J.; Peinado, Victor Ivo; Laclaustra, Martín; Barberá, Joan Albert; Barbas, Coral

    2016-01-01

    Diagnosis of pulmonary arterial hypertension (PAH) is difficult due to the lack of specific clinical symptoms and biomarkers, especially at early stages. We compared plasma metabolic fingerprints of PAH patients (n = 20) with matched healthy volunteers (n = 20) using, for the first time, untargeted multiplatform metabolomics approach consisting of high-performance liquid and gas chromatography coupled with mass spectrometry. Multivariate statistical analyses were performed to select metabolites that contribute most to groups’ classification (21 from liquid in both ionization modes and 9 from gas chromatography-mass spectrometry). We found metabolites related to energy imbalance, such as glycolysis-derived metabolites, as well as metabolites involved in fatty acid, lipid and amino acid metabolism. We observed statistically significant changes in threitol and aminomalonic acid in PAH patients, which could provide new biochemical insights into the pathogenesis of the disease. The results were externally validated on independent case and control cohorts, confirming up to 16 metabolites as statistically significant in the validation study. Multiplatform metabolomics, followed by multivariate chemometric data analysis has a huge potential for explaining pathogenesis of PAH and for searching potential and new more specific and less invasive markers of the disease. PMID:27486806

  4. Veno-venous extracorporeal membrane oxygenation bridging to pharmacotherapy in pulmonary arterial hypertensive crisis.

    PubMed

    Srivastava, Mukta C; Ramani, Gautam V; Garcia, Jose P; Griffith, Bartley P; Uber, Patricia A; Park, Myung H

    2010-07-01

    We report the case of a treatment-naive patient with pulmonary arterial hypertension who presented with decompensated right ventricular failure and cardiogenic shock. Unstable hemodynamics, hypoxia and end-organ hypoperfusion limited up-titration of pharmacotherapy. Mechanical circulatory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO) was initiated to permit dose titration of pulmonary vasodilator therapy. VV-ECMO was weaned after 10 days of support, with successful transition to intravenous epoprostenol and oral sildenafil. PMID:20417127

  5. Relationship Between Carotid Artery Calcification Detected in Dental Panoramic Images and Hypertension and Myocardial Infarction

    PubMed Central

    Moshfeghi, Mahkameh; Taheri, Jamileh Beigom; Bahemmat, Nika; Evazzadeh, Mohammad Ebrahim; Hadian, Hoora

    2014-01-01

    Background: Carotid artery calcification may be related to cerebrovascular accident, which may result in death or physical and mental disabilities in survivors. Objectives: Our purpose is to study the association of carotid artery calcification (CAC) on dental panoramic radiographs and two risk factors of cerebrovascular accident (CVA) including hypertension and myocardial infarction (MI). Patients and Methods: Panoramic images of 200 patients that were all women above 50 years of age (a population suffering from vascular diseases) were investigated. All panoramic images were provided under similar conditions in terms of the type of panoramic radiograph equipment, type of applied films and the automatic film processor. Then, the patients answered questions about MI history and taking antihypertensive drugs. We also measured the blood pressure of patients in two separate surveys. Data analysis was performed by SPSS statistical program. We used Exact Fisher test and Chi-Square test at a significant level of less than 0.05 to study the effect of these variables on the occurrence of carotid artery calcification. Results: Among 200 studied samples, 22 of the patients (11%) had carotid artery calcification on the dental panoramic radiograph. In total, 52 patients (26%) had hypertension and four people (2%) had a history of MI. Eleven individuals among patients suffering from hypertension (21.2%) and three individuals among patients with a history of MI (75%) demonstrated CAC on dental panoramic images . Conclusions: The relationship between CAC found on dental panoramic radiographs and two CVA risk factors--hypertension and MI-- was significant. Therefore, it seems that detection of CAC on panoramic images of dental patients must be considered by dentists. PMID:25763086

  6. Prognostic value of right ventricular ejection fraction in pulmonary arterial hypertension.

    PubMed

    Courand, Pierre-Yves; Pina Jomir, Géraldine; Khouatra, Chahéra; Scheiber, Christian; Turquier, Ségolène; Glérant, Jean-Charles; Mastroianni, Bénédicte; Gentil, Béatrice; Blanchet-Legens, Anne-Sophie; Dib, Alfred; Derumeaux, Geneviève; Humbert, Marc; Mornex, Jean-François; Cordier, Jean-François; Cottin, Vincent

    2015-01-01

    Right ventricle ejection fraction (RVEF) evaluated with magnetic resonance imaging is a strong determinant of patient outcomes in pulmonary arterial hypertension. We evaluated the prognostic value of RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change 3-6 months after initiating pulmonary arterial hypertension-specific therapy. In a prospective cohort of newly diagnosed patients with idiopathic, heritable or anorexigen-associated pulmonary arterial hypertension, RVEF was measured at baseline (n=100) and 3-6 months after initiation of therapy (n=78). After a median follow-up of 4.1 years, 41 deaths occurred, including 35 from cardiovascular causes. Patients with a (median) baseline RVEF >25% had better survival than those with a RVEF <25% using Kaplan-Meier analysis (p=0.010). RVEF at baseline was an independent predictor of all-cause and cardiovascular mortality in adjusted Cox regression model (p=0.002 and p=0.007, respectively; HR 0.93 for both). Patients with stable or increased RVEF at 3-6 months had a trend for improved all-cause survival (HR 2.43, p=0.086) and had less cardiovascular mortality (HR 3.25, p=0.034) than those in whom RVEF decreased despite therapy. RVEF assessed with conventional planar equilibrium radionuclide angiography at baseline and change in RVEF 3-6 months after therapy initiation independently predict outcomes in patients with pulmonary arterial hypertension. PMID:25537560

  7. Pulmonary artery denervation for treatment of a patient with pulmonary hypertension secondary to left heart disease

    PubMed Central

    2016-01-01

    Abstract Pulmonary hypertension (PH) predicts poor outcome in patients with left heart disease. A 62-year-old man was referred for heart failure associated with ischemic cardiomyopathy. He received a diagnosis of combined postcapillary and precapillary PH secondary to left heart disease on the basis of hemodynamic parameters. After the pulmonary artery denervation procedure was performed, hemodynamic parameters were markedly improved, which resulted in a significant increase in functional capacity. PMID:27252851

  8. [Treatment of pulmonary arterial hypertension: endothelin-receptor antagonists].

    PubMed

    Hoeper, M M

    2006-12-01

    Endothelin-1 (ET-1) is of significance in the pathophysiology and prognosis of pulmonary hypertension (PHT). Bosentan, an endothelin-receptor antagonist, currently plays a central role in the treatment of PHT, because it improves exercise capacity, hemodynamics, clinical symptoms and right ventricular function, achieving a survival duration of 2- 3 years. Bosentan causes an increase of transaminases in about 10% of patients, but this effect is reversible on dosage reduction or discontinuing the medication. However, transaminases should be measured every 4 weeks while patients are on bosentan. Almost all current guidelines list bosentan as of equal value to sildenafil or prostacyclin analogues in the first-line treatment of patients in NYHA functional class III and also, with narrower indications, of those in class IV. PMID:17139593

  9. [Anesthetic Management for Lobectomy in a Patient with Pulmonary Arterial Hypertension].

    PubMed

    Imajo, Yukihiro; Komasawa, Nobuyasu; Kusaka, Yusuke; Kido, Haruki; Minami, Toshiaki

    2016-02-01

    Pulmonary arterial hypertension (PAH) is a known risk factor of perioperative complications, but the risks for non-cardiac operations have not yet been examined sufficiently. We report a case of a right lower lobectomy in a patient with PAH. A 73-year-old woman with Sjögren's syndrome was scheduled for right lowr lobectomy for primary lung cancer under general anesthesia. She was diagnosed with symptomatic PAH (estimated mean pulmonary arterial pressure, 40 mmHg) and medicated with ambrisentan. After induction of general anesthesia with propofol and fentanyl, a pulmonary artery catheter was placed to measure pulmonary artery pressure. The Pp/Ps was roughly 0.4 and the pulmonary artery clamp elevated it to 0.5. Milrinone administration gradually improved the Pp/Ps to 0.3. To avoid pulmonary artery pressure elevation during emergence of anesthesia, continuous dexmedetomidine was administered. The double-lumen tracheal tube was extubated uneventfully with minimal elevation in pulmonary arterial pressure. PMID:27017766

  10. Cerebral Perfusion Measurements in Elderly with Hypertension Using Arterial Spin Labeling

    PubMed Central

    Mutsaerts, H. J. M. M.; van Dalen, J. W.; Heijtel, D. F. R.; Groot, P. F. C.; Majoie, C. B. L. M.; Petersen, E. T.; Richard, E.; Nederveen, A. J.

    2015-01-01

    Purpose The current study assesses the feasibility and value of crushed cerebral blood flow (CBFcrushed) and arterial transit time (ATT) estimations for large clinical imaging studies in elderly with hypertension. Material and Methods Two pseudo-continuous arterial spin labeling (ASL) scans with (CBFcrushed) and without flow crushers (CBFnon-crushed) were performed in 186 elderly with hypertension, from which CBF and ATT maps were calculated. Standard flow territory maps were subdivided into proximal, intermediate and distal flow territories, based on the measured ATT. The coefficient of variation (CV) and physiological correlations with age and gender were compared between the three perfusion parameters. Results There was no difference in CV between CBFcrushed and CBFnon-crushed (15–24%, p>0.4) but the CV of ATT (4–9%) was much smaller. The total gray matter correlations with age and gender were most significant with ATT (p = .016 and p<.001 respectively), in between for CBFcrushed (p = .206 and p = .019) and least significant for CBFnon-crushed (p = .236 and p = .100). Conclusion These data show the feasibility and added value of combined measurements of both crushed CBF and ATT for group analyses in elderly with hypertension. The obtained flow territories provide knowledge on vascular anatomy of elderly with hypertension and can be used in future studies to investigate regional vascular effects. PMID:26241897

  11. Diagnosis of pulmonary hypertension from radiographic estimates of pulmonary arterial size.

    PubMed Central

    Bush, A; Gray, H; Denison, D M

    1988-01-01

    The reported accuracy of radiographic measurements in predicting pulmonary hypertension is very variable. Measurements of right and left descending pulmonary artery diameter have been reported to provide a correct diagnosis in as many as 98% of patients. A study was carried out to determine the predictive value of measurements made from the chest radiographs of 50 normal subjects and of 27 patients undergoing right heart catheterisation for cardiac or pulmonary vascular disease, taking account of radiographic magnification. After such corrections a right descending pulmonary artery diameter over 16.7 mm or a left descending pulmonary artery diameter of over 16.9 mm distinguished 12 of 23 pulmonary hypertensive subjects, with no false positive results. The diameter was then arbitrarily squared (any differences between patients and control subjects being exaggerated) and the product was divided by either predicted or actual lung volume in an attempt to correct for body size. The new index distinguished 19 of 23 patients with pulmonary hypertension, with one false positive, when the divisor was actual lung volume; when predicted lung volume was used 18 of 23 patients were distinguished, again with one false positive result. PMID:3353884

  12. Pathological function of Ca2+-sensing receptor in pulmonary arterial hypertension.

    PubMed

    Yamamura, Aya

    2014-01-01

    Pulmonary arterial hypertension (PAH) is defined as an intractable disease characterized by a progressive elevation of pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP), leading to right heart failure and premature death. The five-year survival rate after diagnosis is approximately 57%. Although extensive research has identified some factors associated with the cause of PAH, the etiology and pathogenesis remain unclear. In addition to Ca(2+) channel blockers (nifedipine, diltiazem), three categories of drug have been developed for the treatment of PAH based on the pathological mechanisms: prostacyclin and its analogues (epoprostenol, treprostinil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan), and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). However, screening of novel types of drug acting on the signal pathway associated with the pathological mechanism underlying PAH is ongoing. We recently found that the extracellular Ca(2+)-sensing receptor (CaSR), which belongs to family C of the G protein-coupled receptor (GPCR) superfamily, is upregulated in pulmonary arterial smooth muscle cells (PASMCs) from patients with idiopathic PAH (IPAH). The upregulated CaSR is necessary for the enhanced Ca(2+) signaling and the augmented cell proliferation in PASMCs from IPAH patients. Most importantly, blockage of CaSR with an antagonist, NPS2143, prevents the development of pulmonary hypertension and right ventricular hypertrophy in animal models of pulmonary hypertension. The use of calcilytics, antagonists of CaSR, may be a novel therapeutic approach for PAH patients. PMID:24770445

  13. Male Gender and Arterial Hypertension are Plaque Predictors at Coronary Computed Tomography Angiography

    PubMed Central

    Oliveira, Joselina Luzia Menezes; Hirata, Mario Hiroyuki; Sousa, Amanda Guerra de Moraes Rego; Gabriel, Fabíola Santos; Hirata, Thiago Dominguez Crespo; Tavares, Irlaneide da Silva; Melo, Luiza Dantas; Dória, Fabiana de Santana; Sousa, Antônio Carlos Sobral; Pinto, Ibraim Masciarelli Francisco

    2015-01-01

    Background Systemic Arterial Hypertension (SAH) is one of the main risk factors for Coronary Artery Disease (CAD), in addition to male gender. Differences in coronary artery lesions between hypertensive and normotensive individuals of both genders at the Coronary Computed Tomography Angiography (CCTA) have not been clearly determined. Objective To Investigate the calcium score (CS), CAD extent and characteristics of coronary plaques at CCTA in men and women with and without SAH. Methods Prospective cross-sectional study of 509 patients undergoing CCTA for CAD diagnosis and risk stratification, from November 2011 to December 2012, at Instituto de Cardiologia Dante Pazzanese. Individuals were stratified according to gender and subdivided according to the presence (HT +) or absence (HT-) of SAH. Results HT+ women were older (62.3 ± 10.2 vs 57.8 ± 12.8, p = 0.01). As for the assessment of CAD extent, the HT+ individuals of both genders had significant CAD, although multivessel disease is more frequent in HT + men. The regression analysis for significant CAD showed that age and male gender were the determinant factors of multivessel disease and CS ≥ 100. Plaque type analysis showed that SAH was a predictive risk factor for partially calcified plaques (OR = 3.9). Conclusion Hypertensive men had multivessel disease more often than women. Male gender was a determinant factor of significant CAD, multivessel disease, CS ≥ 100 and calcified and partially calcified plaques, whereas SAH was predictive of partially calcified plaques. PMID:25861034

  14. Doppler Flow Wire Evaluation of Renal Blood Flow Reserve in Hypertensive Patients with Normal Renal Arteries

    SciTech Connect

    Beregi, Jean-Paul; Mounier-Vehier, Claire; Devos, Patrick; Gautier, Corinne; Libersa, Christian; McFadden, Eugene P.; Carre, Alain

    2000-09-15

    Purpose: To study the vasomotor responses of the renal microcirculation in patients with essential hypertension.Methods: We studied the reactivity of the renal microcirculation to papaverine, with intraarterial Doppler and quantitative arteriography, in 34 renal arteries of 19 hypertensive patients without significant renal artery stenosis. Isosorbide dinitrate was given to maximally dilate proximal renal arteries. APV (average peak blood flow velocity) was used as an index of renal blood flow.Results: Kidneys could be divided into two distinct subgroups based on their response to papaverine. An increase in APV of up to 55% occurred in 21 kidneys, an increase > 55% in 13 kidneys. Within each group the values were normally distributed. Both baseline APV and the effect of papaverine on mean velocity differed significantly between groups.Conclusion: There seems to be a subgroup of patients with essential hypertension that has an impaired reactivity to papaverine, consistent with a functional impairment of the renal microcirculation. Further studies are required to determine whether this abnormality contributes to or results from elevated blood pressure.

  15. Regulation of Cell Cycle Regulators by SIRT1 Contributes to Resveratrol-Mediated Prevention of Pulmonary Arterial Hypertension

    PubMed Central

    Zhou, Shuang; Li, Meng-Tao; Jia, Yu-Yan; Liu, Jin-Jing; Wang, Qian; Tian, Zhuang; Liu, Yong-Tai; Chen, Hou-Zao; Liu, De-Pei; Zeng, Xiao-Feng

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in rheumatic diseases. Vascular remodeling due to the proliferation of pulmonary arterial smooth muscle cells (PASMCs) is central to the development of PAH. To date, it is still unclear if Silence Information Regulator 1 (SIRT1) regulates cell cycle regulators in the proliferation of PASMCs and contributes to prevention of PAH by resveratrol. In this study, we found that a significant decrease of SIRT1 expression levels in platelet-derived growth factor BB (PDGF-BB) treated human PASMCs (HPASMCs) and in monocrotaline (MCT) induced PAH rat. Overexpression of SIRT1 induced G1 phase arrest and increased p21 expression but decreased cyclin D1 expression in PDGF-BB treated HPASMCs. Moreover, resveratrol attenuated pulmonary arterial remodeling, decreased pulmonary arterial pressure, and upregulated SIRT1 and p21 expression but downregulated cyclin D1 expression in MCT induced PAH rat. Notably, knockdown of SIRT1 eliminated the regulation of resveratrol on p21 and cyclin D1 expression in PDGF-BB treated HPASMCs. These results demonstrated that SIRT1 mediated the regulation of resveratrol on the expression of cell cycle regulatory molecules. It suggests that SIRT1 exerts a protective role in PAH associated with rheumatic diseases and can be a potential treatment target. PMID:26273643

  16. Increased plasma neopterin levels are associated with reduced endothelial function and arterial elasticity in hypertension.

    PubMed

    Zhang, Y-Y; Tong, X-Z; Xia, W-H; Xie, W-L; Yu, B-B; Zhang, B; Chen, L; Tao, J

    2016-07-01

    Inflammation has been shown to play a pivotal role in the pathogenesis and development of hypertensive vascular injury. Neopterin is a novel marker of immune activation produced mainly by activated macrophages. Few data are available to show the association between neopterin and vascular function in hypertension. The present study was designed to investigate the relationship between neopterin levels related to arterial stiffness and endothelial function in patients with hypertension, and their changes after blood pressure-lowering treatment. Twenty-four hypertensive patients and 30 age- and gender-matched healthy volunteers were recruited. Plasma neopterin levels were higher in hypertensive patients compared with their counterparts (log-neopterin: 0.77±0.18 versus 0.61±0.16, P=0.003). Increased neopterin levels were correlated with increased brachial-ankle pulse wave velocity (baPWV; control: r=0.659, P<0.001; hypertension: r=0.487, P=0.021), and inversely associated with impaired brachial flow-mediated dilation (FMD; control: r=-0.735, P<0.001; hypertension: r=-0.557, P=0.005). Fifteen hypertensives received 3 months of standard antihypertensive treatment. Three months later, their plasma neopterin levels decreased (log-neopterin: 0.63±0.17 versus 0.50±0.19, P=0.001), whereas arterial elasticity (baPWV: 1764±101 versus 1685±96 cm s(-1), P=0.272) and endothelial function (FMD: 5.92±1.43% versus 7.73±1.31%, P<0.05) were improved. The decline in neopterin levels was linearly correlated with baPWV decrease (r=0.800, P<0.001), FMD improvement (r=0.670, P=0.006) and blood pressure reduction (r=0.548, P=0.042). Our present study demonstrated for the first time that neopterin is closely correlated with vascular dysfunctions, and measurement of plasma neopterin levels might be used as a surrogate biomarker for the clinical evaluation of vascular damage and risk stratification of future atherosclerotic cardiovascular disease in patients with hypertension. PMID

  17. Pulmonary Hypertension Due to Common Respiratory Conditions: Classification, Evaluation and Management Strategies.

    PubMed

    Fein, Daniel G; Zaidi, Ali N; Sulica, Roxana

    2016-01-01

    Pulmonary hypertension (PH) due to chronic respiratory disease and/or hypoxia is classified as World Health Organization (WHO) Group III pulmonary hypertension. The patients most commonly encountered in clinical practice with group III PH include those with chronic obstructive lung disease (COPD), diffuse parenchymal lung disease, and sleep-disordered breathing. The purpose of this review is to outline the variable clinical significance of pulmonary hypertension in the most common pulmonary disease states and how a clinician may approach the management of these patients. PMID:27571110

  18. [Obesity as pathology of adipocytes: number of cells, volume of arterial bloodstream,local pools of circulation in vivo, natriuretic peptides and arterial hypertension].

    PubMed

    Titov, V N; Dmitriev, V A

    2015-03-01

    The non-specific systemic biological reaction of arterial pressure from the level of organism. vasomotor center and proximal section of arterial bloodstream is appealed to compensate disorders of metabolism and microcirculation in distal section of arteries. This phenomenon occurs in several cases. The primarily local disorders of metabolism at autocrine level, physiological (aphysiological) death of cells, "littering" of intercellular medium become the cause of disorder of microcirculation in paracrin cenosises and deteriorate realization of biological functions of homeostasis, trophology, endoecology and adaptation. The local compensation of affected perfusion in paracrin cenosises at the expense of function of peripheral peristaltic pumps, redistribution of local bloodflow in biological reaction of endothelium-depended vaso-dilation has no possibility to eliminate disorders in realization of biological functions. The systemic increase of arterial pressure under absence of specific symptoms of symptomatic arterial hypertension is a test to detect disorder of biological functions of homeostasis, trophology, biological function of endoecology and adaptation. Allforms of arterial hypertension develop by common algorithm independently from causes of disorders of blood flow, microcirculation in distal section of arteries. The non-specific systemic compensation ofdisorders of metabolism from level of organism, in proximal section of arterial bloodstream always is the same one and results in aphysiological alterations in organs-targets. To comprehend etiological characteristics of common pathogenesis of arterial hypertension is possible in case of application of such technically complicated and still unclear in differential diagnostic of deranged functions modes of metabolomics. PMID:26031157

  19. Pulmonary hypertension due to obstructive sleep apnea in a child with Rubinstein-Taybi syndrome.

    PubMed

    Choi, Hyung Soon; Yu, Jeong Jin; Kim, Young-Hwue; Ko, Jae-Kon; Park, In-Sook

    2012-06-01

    Rubinstein-Taybi syndrome (RTS) is characterized by peculiar facies, mental retardation, broad thumbs, and great toes. Approximately one-third of the affected individuals have a variety of congenital heart diseases. They can also have upper airway obstruction during sleep, due to hypotonia and the anatomy of the oropharynx and airway, which make these patients susceptible to obstructive sleep apnea (OSA). In our case, pulmonary hypertension was caused, successively, by congenital heart defects (a large patent ductus arteriosus and arch hypoplasia) and obstructive sleep apnea during early infancy. The congenital heart defects were surgically corrected, but persistent pulmonary hypertension was identified 2 months after the operation. This pulmonary hypertension was due to OSA, and it was relieved by nasal continuous positive airway pressure. This case is the first report of pulmonary hypertension from OSA in a young infant with RTS. PMID:22745646

  20. Hypertension - overview

    MedlinePlus Videos and Cool Tools

    If left untreated, hypertension can lead to the thickening of arterial walls causing its lumen, or blood passage way, to narrow in diameter. ... the narrowed arterial openings. In addition, people with hypertension may be more susceptible to stroke.

  1. [Analysis of a disturbance of trace element balance in patients with ischemic stroke with arterial hypertension].

    PubMed

    Kuramshina, D B; Novikova, L B; Nikonov, A A; Torshin, I Iu; Gromova, O A

    2012-01-01

    Disturbance of trace element balance increases the risk of cerebrovascular disease and, above all, ischemic stroke (IS). A comparative analysis of clinical and demographic parameters and trace element composition of hair was performed in the group of 30 ischemic stroke patients with arterial hypertension (AH) and 30 stroke patients without hypertension (mean age 55±7 years). The stroke patients with hypertension were characterized by the elevated body mass index (28.5±4.1 kg/m2, AI, 26.0±2.9 kg/m2, p=0.006), higher incidence of coronary heart disease (p=0.04). Alcohol consumption more than 3 drinks a week was associated with a 5-fold increase of the risk of stroke with hypertension (95% CI 1.0-27, p=0.035). The results revealed a number of statistically significant differences in trace element profile in the studied groups of patients: deficits of essential magnesium, manganese, cobalt, copper, zinc, a statistically significant increase in sodium levels, toxic and conditionally toxic trace elements (cadmium, mercury, bismuth, barium, etc.). One of the probable factors that lead to the accumulation of toxic trace elements in stroke patients is the increased consumption of alcohol including that of substandard quality. The data obtained also show the feasibility of implementing screening programs to assess micronutrient status (including trace elements) for early detection of pathological abnormalities in the elemental homeostasis that might lead to an increased risk of ischemic stroke and hypertension. PMID:22677769

  2. Bilateral anterior cerebral artery aneurysm due to mucormycosis.

    PubMed

    Kasliwal, Manish K; Reddy, Vemuru Sunil K; Sinha, Sumit; Sharma, Bhawani S; Das, Prasenjit; Suri, Vaishali

    2009-01-01

    True mycotic aneurysms are extremely rare cerebrovascular lesions with a dismal prognosis. They mostly follow fungal meningitis or septicaemia and herald their presence with the development of subarachnoid haemorrhage. The authors report an extremely rare occurrence of bilateral anterior cerebral artery aneurysms caused by mucormycosis. The infection was diagnosed after investigation of prolonged fever following transsphenoidal surgery. The aneurysm was diagnosed after a subarachnoid haemorrhage and the patient finally died. The present case highlights an atypical presentation of fungal infection that can perplex the best of clinicians and thus delay diagnosis. As subarachnoid haemorrhage due to true mycotic aneurysmal rupture is uniformly associated with a fatal outcome, the authors speculate that a high index of suspicion should be maintained when a neurosurgical patient is predisposed to fungal infection. This approach, combined with the empirical institution of antifungal drugs, provides the only chance of survival. PMID:19013802

  3. Renal artery stenosis on duplex ultrasound due to inferior vena cava filter leg impingement

    PubMed Central

    2014-01-01

    We present a case study of renal artery duplex findings for new onset of hypertension in a young woman with a history of inferior vena cava filter placed a year prior and failed percutaneous retrieval. Duplex ultrasound showed significantly elevated velocities in the mid-right renal artery, consistent with renal artery stenosis. Computed tomography angiography images suggested that a leg from the inferior vena cava filter was impinging on her right renal artery, with perforation through the vena cava possibly into the wall of her duodenum. Open surgical intervention was required to disentangle the filter legs from the wall of the duodenum and relieve impingement on the right renal artery with thrombolysis of clot found within the right renal artery.

  4. Alpha 1-adrenoceptors mediating contraction in arteries of normotensive and spontaneously hypertensive rats are of the alpha 1D or alpha 1A subtypes.

    PubMed

    Villalobos-Molina, R; Ibarra, M

    1996-03-18

    Alpha 1-Adrenoceptor subtypes mediating contraction in carotid, aorta, mesenteric and caudal arteries from both Wistar Kyoto (WKY) normotensive and spontaneously hypertensive (SHR) rats were investigated by using the alpha 1A-adrenoceptor agonist methoxamine and antagonized with selective, competitive antagonists WB-4101, 5-methyl urapidil or BMY 7378 (8-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4,5)decane -7,9-dione dihydrochloride). Isometric tension changes were recorded after methoxamine addition to the arterial rings, and the effects of the antagonists determined. All the antagonists shifted to the right the concentration-response curve to methoxamine. pA2 values indicate that all arteries but caudal express the alpha 1D-adrenoceptor subtype, since BMY 7378 values were high in these arteries. Due to the high pA2 values for 5-methyl urapidil and WB-4101 and the low values for BMY 7378 we conclude that the tail artery expresses the alpha 1A and not the alpha 1B subtype. No differences were found between both strains of rats, suggesting that hypertension does not modify the alpha 1-adrenoceptors in conductance arteries. PMID:8846824

  5. Clinical Safety, Pharmacokinetics, and Efficacy of Ambrisentan Therapy in Children With Pulmonary Arterial Hypertension

    PubMed Central

    Takatsuki, Shinichi; Rosenzweig, Erika B.; Zuckerman, Warren; Brady, Daniela; Calderbank, Michelle; Ivy, D. Dunbar

    2012-01-01

    Summary Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, the clinical safety and pharmacokinetics of ambrisentan has not been well studied. Our aim was to investigate the clinical safety, pharmacokinetics, tolerability, and efficacy of endothelin receptor antagonist therapy with ambrisentan in children with pulmonary arterial hypertension (PAH). This retrospective cohort study provides clinical data from pediatric patients with PAH receiving ambrisentan as add-on therapy or transition from bosentan. Safety included evaluation of adverse events including aminotransferase abnormalities. The clinical impact was evaluated by improvement from baseline in clinical variables. A total of 38 pediatric patients with PAH received ambrisentan. Fifteen of 38 patients were switched from bosentan to ambrisentan. The remaining 23 children were treated with ambrisentan as an add-on therapy due to disease progression. In both transition and add-on cases, mean pulmonary artery pressure significantly improved (transition; 55 ± 18 vs. 45 ± 20 mmHg, n = 13, P = 0.04, add-on; 52 ± 17 vs. 45 ± 19 mmHg, n = 13, P = 0.03) during the follow-up. World Health Organization functional class improved in 31% of patients, but one patient required an atrial septostomy due to disease progression during the follow-up period (median, range; 20, 4–44 months). Five patients (13%) discontinued ambrisentan due to severe headache, lack of clinical efficacy, or near syncope. Ten patients (26%) had side effects associated with ambrisentan treatment, including nasal congestion, headache, and flushing. However, no patients had aminotransferase abnormalities and there were no deaths after initiation of ambrisentan during follow-up. Pharmacokinetics were evaluated in sixteen children treated with ambrisentan from 2.5 mg to 10.0 mg; the mean peak plasma concentration was 738 ± 452 ng/ml, mean time to peak plasma concentration was 3.2 ± 2.1 hours, and mean area

  6. Clinical safety, pharmacokinetics, and efficacy of ambrisentan therapy in children with pulmonary arterial hypertension.

    PubMed

    Takatsuki, Shinichi; Rosenzweig, Erika B; Zuckerman, Warren; Brady, Daniela; Calderbank, Michelle; Ivy, D Dunbar

    2013-01-01

    Recent trials in adult PAH revealed the efficacy of ambrisentan. However, in children with PAH, the clinical safety and pharmacokinetics of ambrisentan has not been well studied. Our aim was to investigate the clinical safety, pharmacokinetics, tolerability, and efficacy of endothelin receptor antagonist therapy with ambrisentan in children with pulmonary arterial hypertension (PAH). This retrospective cohort study provides clinical data from pediatric patients with PAH receiving ambrisentan as add-on therapy or transition from bosentan. Safety included evaluation of adverse events including aminotransferase abnormalities. The clinical impact was evaluated by improvement from baseline in clinical variables. A total of 38 pediatric patients with PAH received ambrisentan. Fifteen of 38 patients were switched from bosentan to ambrisentan. The remaining 23 children were treated with ambrisentan as an add-on therapy due to disease progression. In both transition and add-on cases, mean pulmonary artery pressure significantly improved (transition; 55 ± 18 vs. 45 ± 20 mmHg, n = 13, P = 0.04, add-on; 52 ± 17 vs. 45 ± 19 mmHg, n = 13, P = 0.03) during the follow-up. World Health Organization functional class improved in 31% of patients, but one patient required an atrial septostomy due to disease progression during the follow-up period (median, range; 20, 4-44 months). Five patients (13%) discontinued ambrisentan due to severe headache, lack of clinical efficacy, or near syncope. Ten patients (26%) had side effects associated with ambrisentan treatment, including nasal congestion, headache, and flushing. However, no patients had aminotransferase abnormalities and there were no deaths after initiation of ambrisentan during follow-up. Pharmacokinetics were evaluated in sixteen children treated with ambrisentan from 2.5 mg to 10.0 mg; the mean peak plasma concentration was 738 ± 452 ng/ml, mean time to peak plasma concentration was 3.2 ± 2.1 hours, and mean area under the

  7. Increasing pulmonary artery pulsatile flow improves hypoxic pulmonary hypertension in piglets.

    PubMed

    Courboulin, Audrey; Kang, Chantal; Baillard, Olivier; Bonnet, Sebastien; Bonnet, Pierre

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular failure. Current treatments are limited. Physiologically, pulsatile blood flow is detrimental to the vasculature. In response to sustained pulsatile stress, vessels release nitric oxide (NO) to induce vasodilation for self-protection. Based on this observation, this study developed a protocol to assess whether an artificial pulmonary pulsatile blood flow could induce an NO-dependent decrease in pulmonary artery pressure. One group of piglets was exposed to chronic hypoxia for 3 weeks and compared to a control group of piglets. Once a week, the piglets underwent echocardiography to assess PAH severity. At the end of hypoxia exposure, the piglets were subjected to a pulsatile protocol using a pulsatile catheter. After being anesthetized and prepared for surgery, the jugular vein of the piglet was isolated and the catheter was introduced through the right atrium, the right ventricle and the pulmonary artery, under radioscopic control. Pulmonary artery pressure (PAP) was measured before (T0), immediately after (T1) and 30 min after (T2) the pulsatile protocol. It was demonstrated that this pulsatile protocol is a safe and efficient method of inducing a significant reduction in mean PAP via an NO-dependent mechanism. These data open up new avenues for the clinical management of PAH. PMID:25993379

  8. Tetrahydrocurcumin Protects against Cadmium-Induced Hypertension, Raised Arterial Stiffness and Vascular Remodeling in Mice

    PubMed Central

    Sangartit, Weerapon; Kukongviriyapan, Upa; Donpunha, Wanida; Pakdeechote, Poungrat; Kukongviriyapan, Veerapol; Surawattanawan, Praphassorn; Greenwald, Stephen E.

    2014-01-01

    Background Cadmium (Cd) is a nonessential heavy metal, causing oxidative damage to various tissues and associated with hypertension. Tetrahydrocurcumin (THU), a major metabolite of curcumin, has been demonstrated to be an antioxidant, anti-diabetic, anti-hypertensive and anti-inflammatory agent. In this study, we investigated the protective effect of THU against Cd-induced hypertension, raised arterial stiffness and vascular remodeling in mice. Methods Male ICR mice received CdCl2 (100 mg/l) via drinking water for 8 weeks. THU was administered intragastrically at dose of 50 or 100 mg/kg/day concurrently with Cd treatment. Results Administration of CdCl2 significantly increased arterial blood pressure, blunted vascular responses to vasoactive agents, increased aortic stiffness, and induced hypertrophic aortic wall remodeling by increasing number of smooth muscle cells and collagen deposition, decreasing elastin, and increasing matrix metalloproteinase (MMP)-2 and MMP-9 levels in the aortic medial wall. Supplementation with THU significantly decreased blood pressure, improved vascular responsiveness, and reversed the structural and mechanical alterations of the aortas, including collagen and elastin deposition. The reduction on the adverse response of Cd treatment was associated with upregulated eNOS and downregulated iNOS protein expressions, increased nitrate/nitrite level, alleviated oxidative stress and enhanced antioxidant glutathione. Moreover, THU also reduced the accumulation of Cd in the blood and tissues. Conclusions Our results suggest that THU ameliorates cadmium-induced hypertension, vascular dysfunction, and arterial stiffness in mice through enhancing NO bioavailability, attenuating oxidative stress, improving vascular remodeling and decreasing Cd accumulation in other tissues. THU has a beneficial effect in moderating the vascular alterations associated with Cd exposure. PMID:25502771

  9. [Pulmonary hypertension and right ventricular failure. Part XI. Endothelin receptor blockers in the treatment of primary pulmonary arterial hypertension].

    PubMed

    Batyraliev, T A; Makhmutkhodzhaev, S A; Ekinsi, E; Pataraia, S A; Pershukov, I V; Sidorenko, B A; Preobrazhenskiĭ, D V

    2007-01-01

    In a series of articles the authors discuss literature data concerning epidemiology of pulmonary arterial hypertension (PAH), its current classification; peculiarities of its pathogenesis and treatment in various diseases and conditions. In the eleventh communication the authors discuss literature data related to the role of endothelin system in pathogenesis of primary (idiopathic) PAH, as well as PAH associated with diffuse diseases of connective tissue and congenital heart disease. This communication also contains presentation of clinical pharmacology of three available endothelin receptor blockers - bosentan, sitaxsentan, ambrisentan, and analysis of results of randomized controlled trials of efficacy and safety of these agents in patients with idiopathic PAH and PAH associated with diffuse diseases of connective tissue and congenital heart disease. PMID:18260899

  10. HIV protease inhibitors in pulmonary hypertension: rationale and design of a pilot trial in idiopathic pulmonary arterial hypertension

    PubMed Central

    Li, Ying; Li, Xiao-hui; Yu, Zai-xin; Cai, Jing-jing; Billiar, Timothy R.; Chen, Alex F.; Lv, Ben; Chen, Zi-ying; Huang, Zhi-jun; Yang, Guo-ping; Song, Jie; Liu, Bin

    2015-01-01

    Abstract We propose an exploratory clinical study, the first of its kind to our knowledge, to determine the safety and potential clinical benefit of the combination of the HIV protease inhibitors (HIV-PIs) saquinavir and ritonavir (SQV+RIT) in patients with idiopathic pulmonary arterial hypertension (IPAH). This study is based on evidence that (1) HIV-PIs can improve pulmonary hemodynamics in experimental models; (2) both Toll-like receptor 4 and high-mobility group box 1 (HMGB1) participate in the pathogenesis of experimental pulmonary hypertension; and (3) a high-throughput screen for inhibitors of HMGB1-induced macrophage activation yielded HIV-PIs as potent inhibitors of HMGB1-induced cytokine production. In this proposed open-label, pre-post study, micro, low, and standard doses of SQV+RIT will be given to IPAH patients for 14 days. Patients will receive follow-up for the next 14 days. The primary outcome to be evaluated is change in HMGB1 level from baseline at 14 days. The secondary outcome is changes in tumor necrosis factor α, interleukin 1β, interleukin 6, C-reactive protein, pulmonary arterial pressure based on echocardiography parameters and New York Heart Association/World Health Organization functional class, and Brog dyspnea scale index from baseline at 14 days. Other secondary measurements will include N-terminal pro-brain natriuretic peptide, atrial natriuretic peptide, and 6-minute walk distance. We propose that SQV+RIT treatment will improve inflammatory disorders and pulmonary hemodynamics in IPAH patients. If the data support a potentially useful therapeutic effect and suggest that SQV+RIT is safe in IPAH patients, the study will warrant further investigation. (ClinicalTrials.gov identifier: NCT02023450.) PMID:26401255

  11. Comprehensive analysis of myocardial infarction due to left circumflex artery occlusion: comparison with infarction due to right coronary artery and left anterior descending artery occlusion

    SciTech Connect

    Huey, B.L.; Beller, G.A.; Kaiser, D.L.; Gibson, R.S.

    1988-11-01

    Forty consecutive patients with creatine kinase-MB confirmed myocardial infarction due to circumflex artery occlusion (Group 1) were prospectively evaluated and compared with 107 patients with infarction due to right coronary artery occlusion (Group 2) and 94 with left anterior descending artery occlusion (Group 3). All 241 patients underwent exercise thallium-201 scintigraphy, radionuclide ventriculography, 24 h Holter electrocardiographic (ECG) monitoring and coronary arteriography before hospital discharge and were followed up for 39 +/- 18 months. There were no significant differences among the three infarct groups in age, gender, number of risk factors, prevalence and type of prior infarction, Norris index, Killip class and frequency of in-hospital complications. Acute ST segment elevation was present in only 48% of patients in Group 1 versus 71 and 72% in Groups 2 and 3, respectively (p = 0.012), and 38% of patients with a circumflex artery-related infarct had no significant ST changes (that is, elevation or depression) on admission (versus 21 and 20% for patients in Groups 2 and 3, respectively) (p = 0.001). Abnormal R waves in lead V1 were more common in Group 1 than in Group 2 (p less than 0.003) as was ST elevation in leads I, aVL and V4 to V6 (p less than or equal to 0.048). These differences in ECG findings between Group 1 and 2 patients correlated with a significantly higher prevalence of posterior and lateral wall asynergy in the group with a circumflex artery-related infarct. Infarct size based on peak creatine kinase levels and multiple radionuclide variables was intermediate in Group 1 compared with that in Group 2 (smallest) and Group 3 (largest). During long-term follow-up, the probability of recurrent cardiac events was similar in the three infarct groups.

  12. Transpulmonary pressure gradient verifies pulmonary hypertension is initiated by increased arterial resistance in broilers.

    PubMed

    Lorenzoni, A G; Anthony, N B; Wideman, R F

    2008-01-01

    Previous hemodynamic evaluations demonstrated that pulmonary arterial pressure (PAP) is higher in broilers that are susceptible to pulmonary hypertension syndrome (PHS, ascites) than in broilers that are resistant to PHS. We compared key pulmonary hemodynamic parameters in broilers from PHS-susceptible and PHS-resistant lines (selected for 12 generations under hypobaric hypoxia) and in broilers from a relaxed (control) line. In experiment 1 the PAP was measured in male broilers in which a flow probe positioned on one pulmonary artery permitted the determination of cardiac output and pulmonary vascular resistance (PVR). The PAP and relative PVR were higher in susceptible broilers than in relaxed and resistant broilers, whereas absolute and relative cardiac output did not differ between lines. In experiment 2 male and female broilers from the 3 lines were catheterized to measure pressures in the wing vein, right atrium, right ventricle, pulmonary artery, and pulmonary veins (WP, wedge pressure). The transpulmonary pressure gradient (TPG) was calculated as (PAP-WP), with PAP quantifying precapillary pressure and WP approximating postcapillary pulmonary venous pressure. When compared with resistant and relaxed broilers, PAP values in susceptible broilers were > or =10 mmHg higher, TPG values were > or =8 mmHg higher, and WP values were < or =2 mmHg higher, regardless of sex. The combined hemodynamic criteria (elevated PAP and PVR combined with a proportionally elevated TPG) demonstrate that susceptibility to PHS can be attributed primarily to pulmonary arterial hypertension associated with increased precapillary (arteriole) resistance rather than to pulmonary venous hypertension caused by elevated postcapillary (venous and left atrial) resistance. PMID:18079461

  13. Dietary calcium and magnesium supplements in spontaneously hypertensive rats and isolated arterial reactivity.

    PubMed Central

    Mäkynen, H.; Kähönen, M.; Arvola, P.; Wuorela, H.; Vapaatalo, H.; Pörsti, I.

    1995-01-01

    1. High calcium diet attenuates the development of hypertension but an associated undesirable effect is that Mg2+ loss to the urine is enhanced. Therefore, we studied the effects of high calcium diet alone and in combination with increased magnesium intake on blood pressure and arterial function. 2. Forty-eight young spontaneously hypertensive rats (SHR) were allocated into four groups, the dietary contents of Ca2+ and Mg2+ being: 1.1%, 0.2% (SHR); 2.5%, 0.2% (Ca-SHR); 2.5%, 0.8% (CaMg-SHR); and 1.1%, 0.8% (Mg-SHR), respectively. Development of hypertension was followed for 13 weeks, whereafter electrolyte balance, lymphocyte intracellular free calcium ([Ca2+]i), and mesenteric arterial responses in vitro were examined. Forty normotensive Wistar-Kyoto (WKY) rats were investigated in a similar manner. 3. Calcium supplementation comparably attenuated the development of Lypertension during normal and high magnesium intake in SHR, with an associated reduced lymphocyte [Ca2+]i and increased Mg2+ loss to the urine. 4. Endothelium-dependent arterial relaxation to acetylcholine was augmented in Ca-SHR and CaMg-SHR, while the relaxations to isoprenaline and the nitric oxide donor SIN-1 were similar in all SHR groups. Relaxation responses induced by the return of K+ to the organ bath upon precontractions in K(+)-free solution were used to evaluate the function of arterial Na+, K(+)-ATPase. The rate of potassium relaxation was similar in Ca-SHR and CaMg-SHR and faster than in untreated SHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8564205

  14. Perceptions of Received Information, Social Support, and Coping in Patients with Pulmonary Arterial Hypertension or Chronic Thromboembolic Pulmonary Hypertension

    PubMed Central

    Ivarsson, Bodil; Ekmehag, Björn; Hesselstrand, Roger; Rådegran, Göran; Sjöberg, Trygve

    2014-01-01

    Patients with a life-limiting diagnosis of pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) need disease-specific information, ability to cope, and functioning social networks. This cohort study investigated the experiences of PAH and CTEPH patients who received information about their diagnosis, treatment, and management, in addition to coping and social support. Sixty-eight adult patients (mean ± SD, age 67 ± 14; 66% women) were included. A total of 54% of the patients wanted more information. Patients received information mostly in areas concerning medical test procedures, the diagnosis, disease severity, possible disease causes, and how to manage their disease. Coping ability was significantly better in patients who were satisfied with the received information (P = 0.0045). The information given to PAH or CTEPH patients and their communication with healthcare professionals can be greatly improved. Gaps in information and misunderstandings can be avoided by working in cooperation with the patients, their relatives, and within the PAH team. PMID:25374462

  15. Hypoxic acidemia, hyperviscosity, and maternal hypertension do not affect the umbilical arterial velocity waveform in fetal sheep.

    PubMed

    Morrow, R J; Adamson, S L; Bull, S B; Ritchie, J W

    1990-10-01

    The effect of hypoxic acidemia, hyperviscosity, and maternal hypertension on the umbilical arterial velocity waveform was studied in 23 chronically catheterized fetal sheep. Fetal hypoxic acidemia induced by lowering the maternal inspired oxygen concentration (n = 7) caused no change in the ratio of systolic/diastolic blood velocity even when fetal arterial pH was as low as 6.8. Fetal blood hyperviscosity (n = 7) induced by exchange transfusion with packed maternal blood cells increased placental vascular resistance by greater than or equal to 50% but had no significant effect on the systolic/diastolic ratio. Similarly, maternal hypertension induced by intravenous infusion of angiotensin II to the ewe (n = 9) did not affect the systolic/diastolic ratio despite a 50% increase in maternal arterial blood pressure. We conclude that umbilical arterial velocity waveform abnormalities observed in growth-restricted human fetuses are probably not a direct result of fetal hypoxemia or hyperviscosity or maternal hypertension. PMID:2220943

  16. Pulmonary Arterial Hypertension in Adults: Novel Drugs and Catheter Ablation Techniques Show Promise? Systematic Review on Pharmacotherapy and Interventional Strategies

    PubMed Central

    Gaudio, Carlo; Greco, Cesare; Keylani, Abdul M.; D'Agostino, Darrin C.

    2014-01-01

    This systematic review aims to provide an update on pharmacological and interventional strategies for the treatment of pulmonary arterial hypertension in adults. Currently US Food and Drug Administration approved drugs including prostanoids, endothelin-receptor antagonists, phosphodiesterase type-5 inhibitors, and soluble guanylate-cyclase stimulators. These agents have transformed the prognosis for pulmonary arterial hypertension patients from symptomatic improvements in exercise tolerance ten years ago to delayed disease progression today. On the other hand, percutaneous balloon atrioseptostomy by using radiofrequency perforation, cutting balloon dilatation, or insertion of butterfly stents and pulmonary artery catheter-based denervation, both associated with very low rate of major complications and death, should be considered in combination with specific drugs at an earlier stage rather than late in the progression of pulmonary arterial hypertension and before the occurrence of overt right-sided heart failure. PMID:25013799

  17. Changes in the structure-function relationship of elastin and its impact on the proximal pulmonary arterial mechanics of hypertensive calves.

    PubMed

    Lammers, Steven R; Kao, Phil H; Qi, H Jerry; Hunter, Kendall; Lanning, Craig; Albietz, Joseph; Hofmeister, Stephen; Mecham, Robert; Stenmark, Kurt R; Shandas, Robin

    2008-10-01

    Extracellular matrix remodeling has been proposed as one mechanism by which proximal pulmonary arteries stiffen during pulmonary arterial hypertension (PAH). Although some attention has been paid to the role of collagen and metallomatrix proteins in affecting vascular stiffness, much less work has been performed on changes in elastin structure-function relationships in PAH. Such work is warranted, given the importance of elastin as the structural protein primarily responsible for the passive elastic behavior of these conduit arteries. Here, we study structure-function relationships of fresh arterial tissue and purified arterial elastin from the main, left, and right pulmonary artery branches of normotensive and hypoxia-induced pulmonary hypertensive neonatal calves. PAH resulted in an average 81 and 72% increase in stiffness of fresh and digested tissue, respectively. Increase in stiffness appears most attributable to elevated elastic modulus, which increased 46 and 65%, respectively, for fresh and digested tissue. Comparison between fresh and digested tissues shows that, at 35% strain, a minimum of 48% of the arterial load is carried by elastin, and a minimum of 43% of the change in stiffness of arterial tissue is due to the change in elastin stiffness. Analysis of the stress-strain behavior revealed that PAH causes an increase in the strains associated with the physiological pressure range but had no effect on the strain of transition from elastin-dominant to collagen-dominant behavior. These results indicate that mechanobiological adaptations of the continuum and geometric properties of elastin, in response to PAH, significantly elevate the circumferential stiffness of proximal pulmonary arterial tissue. PMID:18660454

  18. Effects of lung recruitment maneuvers on splanchnic organ perfusion during endotoxin-induced pulmonary arterial hypertension.

    PubMed

    Daudel, Fritz; Gorrasi, José; Bracht, Hendrik; Brandt, Sebastian; Krejci, Vladimir; Jakob, Stephan M; Takala, Jukka; Rothen, Hans Ulrich

    2010-11-01

    Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. Systemic, regional, and organ blood flows were monitored. After 6 h (= baseline), a recruitment maneuver was performed with sustained inflation of the lungs. Thereafter, the pigs were randomly assigned to group C (control, n = 6) or group E with endotoxin-induced pulmonary arterial hypertension (n = 6). Endotoxemia resulted in a normotensive and hyperdynamic state and a deterioration of the oxygenation index by 33%. The RM was then repeated in both groups. Pulmonary artery pressure increased during lipopolysaccharide infusion from 17 ± 2 mmHg (mean ± SD) to 31 ± 10 mmHg and remained unchanged in controls (P < 0.05). During endotoxemia, RM decreased aortic pulse pressure from 37 ± 14 mmHg to 27 ± 13 mmHg (mean ± SD, P = 0.024). The blood flows of the renal artery, hepatic artery, celiac trunk, superior mesenteric artery, and portal vein decreased to 71% ± 21%, 69% ± 20%, 76% ± 16%, 79% ± 18%, and 81% ± 12%, respectively, of baseline flows before RM (P < 0.05 all). Organ perfusion of kidney cortex, kidney medulla, liver, and jejunal mucosa in group E decreased to 65% ± 19%, 77% ± 13%, 66% ± 26%, and 71% ± 12%, respectively, of baseline flows (P < 0.05 all). The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and

  19. Prevalence and predictors of atherosclerotic renal artery stenosis in hypertensive patients undergoing simultaneous coronary and renal artery angiography; a cross-sectional study

    PubMed Central

    Payami, Babak; Jafarizade, Mehrian; Beladi Mousavi, Seyed Seifollah; Sattari, Shahab-Aldin; Nokhostin, Forough

    2016-01-01

    Introduction: According to the non-specific presentation of atherosclerotic renal artery stenosis (ARAS), this disease is usually an under-diagnosed in clinical conditions. Objectives: The aim of the presence study was to evaluate the prevalence of renal artery stenosis (RAS) and its related risk factors in hypertensive patients undergoing coronary angiography. Patients and Methods: In a cross-sectional study, between March 2009 and October 2010, all of hypertensive patients candidate for diagnostic cardiac catheterization, underwent nonselective renal angiography before completion of their coronary angiography procedure. A standardized questionnaire was used to collect demographics, cardiac history, indications for cardiac catheterization and angiographic data. The degree of ARAS was estimated visually by skilled cardiologist. Narrowing greater than 50% of the arterial lumen considered as arterial stenosis. Data was analyzed by SPSS version 19, and by chi-square test and logistic regression model. Results: In overall 274 patients with mean age of 60.75 ± 10.92 years 108 (39.4%) were male and 166 (60.61%) were female. The prevalence of ARAS calculated 18.2%. According to the present study, heart failure and smoking were predictors of ARAS. However, old age, gender, diabetes mellitus, hyperlipidemia and family history of cardiovascular disease were not clinical predictors of significant ARAS in hypertensive patients, candidate for coronary angiography. Conclusion: According to present data, we suggest to consider renal artery angiography in combination with coronary artery angiography especially in hypertensive patients who are smoker or individuals who have heart failure. PMID:27069966

  20. Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension

    PubMed Central

    Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M. Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A.C.

    2016-01-01

    Background— The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. Methods and Results— By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. Conclusions— RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. PMID:27370069

  1. [Blood glucose and insulin in arterial hypertension. The elderly hypertensive patient].

    PubMed

    Fonseca, T; Clara, J G; Bicho, M; Azevedo, M; Manso, C; da Costa, J N

    1993-11-01

    The clinical importance of relationship between insulin resistance, hyperinsulinemia and high blood pressure is not yet fully understood. The aim of this study was to evaluate the influence of age in the relation between hyperglycemia, hyperinsulinemia and hypertension (HT). Two groups of patients with moderate to severe essential hypertension, aged < 65 (n = 40) and > or = 65 (n = 55) were compared with two other groups of normotensive subjects (NT) matched for sex (n = 14) and age (n = 18). The radioimmunoassay method and glucose oxidase methods were used to evaluate plasma insulin and plasma glucose concentrations. The global analysis shows: The plasma glucose level was significantly lower (p < 0.02) in NT group (n = 32; glycemia: 67.52 +/- 44 mg/dl) than in the HT group (n = 95; glycemia: 86.25 +/- 34.7 mg/dl. Further more the plasma insulin level in NT (3.37 +/- 3.18 microU/ml) was also lower than in HT (4.29 +/- 3.08 microU/ml) although without statistical significance. The patients (HT) aged < 65 years old had higher glycemia (85.76 +/- 26.8 mg/dl) and insulinemia (4.92 +/- 3.56) than NT of same age (glycemia: 59.0 +/- 11.8 mg/dl, insulinemia: 2.86 +/- 1.86), respectively p < 0.001 and p < 0.05. In HT aged > or = 65 the glycemia (82.38 +/- (9.67 mg/dl) was higher than in the NT matched group (65.5 +/- 20.36 mg/dl), p < 0.01, but plasma insulin was not different in the two groups (3.88 +/- 2.63 and 3.80 +/- 2.27 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8305245

  2. [Indications for angiographic study of renal arteries in elderly hypertensive subjects].

    PubMed

    Joannides, R; Godin, M; Ziani, A; Dhib, M; Moulin, B; Daoud, M; Louvel, J P; Janvresse, A; Fillastre, J P

    1991-08-01

    During a 30 months period, 70 patients (60-84 years old) underwent a renal artery angiographic investigation, either by combined intravenous angiography and pyelography, either by intravenous or intra-arterial digital angiography. Thirty-nine were males, 31 were females. All patients were hypertensive. Thirty-three had a normal renal function and 37 had a renal insufficiency arbitrarily definite as creatinine clearance lower than 60 ml/min (m = 33 +/- 15 ml/min). Eight aortic anevrysms were discovered. Thirteen patients (18.6%) had atherosclerotic renovascular disease. Criteria which led to undertake these investigations and results are listed in the following table. [table; see text] Transluminal percutaneous angioplasty and surgical treatment were performed 7 and 3 times respectively. In one case, nephrectomy was done. In all these patients but one, improvement of hypertension and/or renal function occurred. In patients with renal impairment, difference in size between the two kidneys detected by echography or plain abdominal X-rays were noted in 8 among the 9 patients with renovascular disease; six among them had proteinuria less than 0.5 g/day. In conclusion, in hypertensive patients older than 60, criteria for detection of renovascular disease are the same as in younger patients. When renal function is decreased, difference in size between the two kidneys requires an angiographic evaluation. Proteinuria does not exclude renovascular pathology. PMID:1835359

  3. Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension.

    PubMed

    Schiffrin, Ernesto L

    2015-01-01

    This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease. PMID:26654522

  4. Low-Sodium DASH Diet Reduces Blood Pressure, Arterial Stiffness, and Oxidative Stress in Hypertensive HFPEF

    PubMed Central

    Hummel, Scott L.; Seymour, E. Mitchell; Brook, Robert D.; Kolias, Theodore J.; Sheth, Samar S.; Rosenblum, Hannah R.; Wells, Joanna M.; Weder, Alan B.

    2012-01-01

    Recent studies suggest that oxidative stress and vascular dysfunction contribute to heart failure with preserved ejection fraction (HFPEF). In ‘salt-sensitive’ HFPEF animal models, diets low in sodium and high in potassium, calcium, magnesium, and antioxidants attenuate oxidative stress and cardiovascular damage. We hypothesized that the sodium-restricted Dietary Approaches to Stop Hypertension diet (DASH/SRD) would have similar effects in human hypertensive HFPEF. Thirteen patients with treated hypertension and compensated HFPEF consumed the DASH/SRD for 21 days (all food/most beverages provided). The DASH/SRD reduced clinic systolic (155 to 138 mmHg, p=.02) and diastolic BP (79 to 72 mmHg, p=.04), 24-hour ambulatory systolic (130 to 123 mmHg, p=.02) and diastolic BP (67 to 62 mmHg, p=.02), and carotid-femoral pulse wave velocity (12.4 to 11.0 m/s, p=.03). Urinary F2-isoprostanes decreased by 31% (209 to 144 pmol/mmol Cr, p=.02) despite increased urinary aldosterone excretion. The reduction in urinary F2-isoprostanes closely correlated with the reduction in urinary sodium excretion on the DASH/SRD. In this cohort of HFPEF patients with treated hypertension, the DASH/SRD reduced systemic blood pressure, arterial stiffness, and oxidative stress. These findings are characteristic of ‘salt-sensitive’ hypertension, a phenotype present in many HFPEF animal models, and suggest shared pathophysiological mechanisms linking these two conditions. Further dietary modification studies could provide insights into the development and progression of hypertensive HFPEF. PMID:23033371

  5. Impairment of endothelial SKCa channels and of downstream hyperpolarizing pathways in mesenteric arteries from spontaneously hypertensive rats

    PubMed Central

    Weston, AH; Porter, EL; Harno, E; Edwards, G

    2010-01-01

    Background and purpose: Previous studies have shown that endothelium-dependent hyperpolarization of myocytes is reduced in resistance arteries from spontaneously hypertensive rats (SHRs). The aim of the present study was to determine whether this reflects down-regulation of endothelial K+ channels or their associated pathways. Experimental approach: Changes in vascular K+ channel responses and expression were determined by a combination of membrane potential recordings and Western blotting. Key results: Endothelium-dependent myocyte hyperpolarizations induced by acetylcholine, 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) (opens small- and intermediate-conductance calcium-sensitive K+ channels, SKCa and IKCa, respectively) or cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine (SKCa opener) were reduced in mesenteric arteries from SHRs. After blocking SKCa channels with apamin, hyperpolarizations to acetylcholine and NS309 in SHR arteries were similar to those of controls. Hyperpolarization to 5 mM KCl was reduced in SHR arteries due to loss of the Ba2+-sensitive, inward-rectifier channel (KIR) component; the contribution of ouabain-sensitive, Na+/K+-ATPases was unaffected. Protein expression of both SKCa and KIR channels was reduced in SHR arteries; the caveolin-1 monomer/dimer ratio was increased. Conclusions and implications: In SHRs, the distinct pathway that generates endothelium-dependent hyperpolarization in vascular myocyte by activation of IKCa channels and Na+/K+-ATPases remains intact. The second pathway, initiated by endothelial SKCa channel activation and amplified by KIR opening on both endothelial cells and myocytes is compromised in SHRs due to down-regulation of both SKCa and KIR and to changes in caveolin-1 oligomers. These impairments in the SKCa–KIR pathway shed new light on vascular control mechanisms and on the underlying vascular changes in hypertension. This article is commented on by Garland, pp. 833–835 of this

  6. Correlations between serum zinc concentrations and oxygen balance parameters in patients with primary arterial hypertension.

    PubMed

    Tubek, Slawomir

    2007-03-01

    It has been postulated that increased blood pressure is related to hypersensitivity of arterial chemoreceptors and increased tissue oxygen supply. Arterial blood pressure has been found to be negatively correlated to serum zinc and positively correlated to age, body mass index, and hemoglobin concentrations. The aim of the present investigation was to further explore the relationship between blood pressure and zinc concentrations in serum and blood morphology parameters, iron concentrations, and venous blood gasometry parameters. The study was carried out in two groups. Group Aconsisted of 23 subjects of both sexes suffering from moderate to severe arterial blood pressure. Their mean age was 53.13+/-10.45 yr (range: 23-74 yr). Group B included 48 subjects of mean age 36.7+/-10.0 yr (range: 26-60 yr). This group included 5 patients with arterial hypotension, 37 with hypertension, and the remaining 6 with normal blood pressure. Significant positive correlations between serum zinc and red blood cell count (r = 0.51) and negative with age (r = -0.52) were found. By multiple regression, negative correlations were also found between serum zinc and the diastolic blood pressure and with hemoglobin (r = -0.5). Age was positively correlated to systolic (r = 0.49) and diastolic (r = 0.45) blood pressure parameters and to hemoglobin concentrations (r = 0.33 and r = 0.38, respectively). Buffered and excess bases in blood were negatively correlated to zinc (r = -0.29 in both cases) and to systolic and diastolic blood pressure (r = -0.31 and r = -0.40, respectively). In turn, the systolic and diastolic blood pressure also correlated negatively to the partial pressure of carbon dioxide and positively to venous blood oxygen saturation and to the partial pressure of oxygen. The role of zinc and acid-balance realtionships in blood pressure regulation and in arterial hypertension ethiopatogenesis is disscused. PMID:17625242

  7. Control of intraoperative hypertension with isoflurane in patients with coronary artery disease: effects on regional myocardial blood flow and metabolism.

    PubMed

    Sahlman, L; Milocco, I; Appelgren, L; William-Olsson, G; Ricksten, S E

    1989-02-01

    The effect of isoflurane on regional myocardial metabolism and blood flow, when used as an adjunct to fentanyl-nitrous oxide anesthesia, to control intraoperative hypertension was investigated. Twenty-two patients with two- or three-vessel coronary artery disease with an ejection fraction greater than 0.5 and on beta-blockers up to the morning of surgery were studied during elective coronary artery by-pass grafting. Systemic and pulmonary hemodynamics, and regional (great cardiac vein, GCVF) myocardial blood flow and myocardial metabolic parameters were measured. In 10 patients, both GCVF and global (coronary sinus, CSF) myocardial blood flows were recorded. Measurements were made 1) after induction of anesthesia but prior to skin incision, 2) during sternotomy, and 3) during isoflurane administration after its use to reduce arterial pressure to the presternotomy level. The increase in systemic arterial pressure during sternotomy was due to an increase in systemic vascular resistance accompanied by increases in heart rate, pulmonary capillary wedge pressure, (PCWP) regional myocardial oxygen consumption and extraction, GCVF and total coronary vascular resistance. Isoflurane reduced systemic arterial pressure but not PCWP, to presternotomy levels within 6.9 +/- 0.7 minutes at an end-tidal concentration of 1.5 +/- 0.2%. Isoflurane induced a pronounced systemic and coronary vasodilatation and increases in cardiac index, heart rate and regional myocardial oxygen extraction while the GCVF/CSF ratio remained unchanged. While mean regional--MLE% values were not effected by sternotomy, in two patients myocardial lactate production was seen during sternotomy but not during isoflurane. In another two patients, isoflurane induced lactate production.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2783640

  8. Pulmonary stenosis development and reduction of pulmonary arterial hypertension in atrioventricular septal defect: a case report

    PubMed Central

    Barth, Emeline; Bouvaist, Hélène; Marlière, Stéphanie; Ninet, Gérard; Vanzetto, Gérald

    2009-01-01

    A 24-year-old patient was admitted for dyspnoea and syncope. He had a previous history of complete atrio-ventricular septal defect and trisomy 21. At the age of 6 months, in 1984, cardiac catheterization revealed a quasi-systemic pulmonary arterial hypertension with a bidirectional shunt corresponding to an Eisenmenger syndrome. Corrective cardiac surgery was not performed at this time because surgical risk was considered too high. Until the age of 20 years old, he showed few symptoms while under medical treatment. But since 2006, his functional status became worse with an increased dyspnoea, syncopes, and severe cyanosis. In these conditions, haemodynamic parameters have been re-evaluated in 2006 and 2008. They highlighted a late and progressive development of a valvular and infundibular pulmonary stenosis leading to a normalisation of pulmonary arterial pressures. At the age of 24 , the patient underwent corrective cardiac surgery which was successful. Late development of both infundibular and valvular pulmonary stenosis have not been described before in non operated congenital ventricular septal defects, but development of one or the other abnormality would be found in 8% of patients. The physiopathological mechanism of this obstruction is unclear. Nevertheless, in unoperated congenital cardiac shunt lesions, reversibility of severe pulmonary arterial hypertension should be reconidered and re-assessed during follow up. PMID:19758423

  9. Calorie Restriction Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

    PubMed Central

    Ding, Mingge; Lei, Jingyi; Qu, Yinxian; Zhang, Huan; Xin, Weichuan; Ma, Feng; Liu, Shuwen; Li, Zhichao; Jin, Faguang

    2015-01-01

    Abstract: Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH. PMID:25636073

  10. Priming Mesenchymal Stem Cells with Endothelial Growth Medium Boosts Stem Cell Therapy for Systemic Arterial Hypertension

    PubMed Central

    de Oliveira, Lucas Felipe; Almeida, Thalles Ramos; Ribeiro Machado, Marcus Paulo; Cuba, Marilia Beatriz; Alves, Angélica Cristina; da Silva, Marcos Vinícius; Rodrigues Júnior, Virmondes; Dias da Silva, Valdo José

    2015-01-01

    Systemic arterial hypertension (SAH), a clinical syndrome characterized by persistent elevation of arterial pressure, is often associated with abnormalities such as microvascular rarefaction, defective angiogenesis, and endothelial dysfunction. Mesenchymal stem cells (MSCs), which normally induce angiogenesis and improve endothelial function, are defective in SAH. The central aim of this study was to evaluate whether priming of MSCs with endothelial growth medium (EGM-2) increases their therapeutic effects in spontaneously hypertensive rats (SHRs). Adult female SHRs were administered an intraperitoneal injection of vehicle solution (n = 10), MSCs cultured in conventional medium (DMEM plus 10% FBS, n = 11), or MSCs cultured in conventional medium followed by 72 hours in EGM-2 (pMSC, n = 10). Priming of the MSCs reduced the basal cell death rate in vitro. The administration of pMSCs significantly induced a prolonged reduction (10 days) in arterial pressure, a decrease in cardiac hypertrophy, an improvement in endothelium-dependent vasodilation response to acetylcholine, and an increase in skeletal muscle microvascular density compared to the vehicle and MSC groups. The transplanted cells were rarely found in the hearts and kidneys. Taken together, our findings indicate that priming of MSCs boosts stem cell therapy for the treatment of SAH. PMID:26300922

  11. A Novel Vascular Homing Peptide Strategy to Selectively Enhance Pulmonary Drug Efficacy in Pulmonary Arterial Hypertension

    PubMed Central

    Toba, Michie; Alzoubi, Abdallah; O’Neill, Kealan; Abe, Kohtaro; Urakami, Takeo; Komatsu, Masanobu; Alvarez, Diego; Järvinen, Tero A.H.; Mann, David; Ruoslahti, Erkki; McMurtry, Ivan F.; Oka, Masahiko

    2015-01-01

    A major limitation in the pharmacological treatment of pulmonary arterial hypertension (PAH) is the lack of pulmonary vascular selectivity. Recent studies have identified a tissue-penetrating homing peptide, CARSKNKDC (CAR), which specifically homes to hypertensive pulmonary arteries but not to normal pulmonary vessels or other tissues. Some tissue-penetrating vascular homing peptides have a unique ability to facilitate transport of co-administered drugs into the targeted cells/tissues without requiring physical conjugation of the drug to the peptide (bystander effect). We tested the hypothesis that co-administered CAR would selectively enhance the pulmonary vascular effects of i.v. vasodilators in Sugen5416/hypoxia/normoxia-exposed PAH rats. Systemically administered CAR was predominantly detected in cells of remodeled pulmonary arteries. Intravenously co-administered CAR enhanced pulmonary, but not systemic, effects of the vasodilators, fasudil and imatinib, in PAH rats. CAR increased lung tissue imatinib concentration in isolated PAH lungs without increasing pulmonary vascular permeability. Sublingual CAR was also effective in selectively enhancing the pulmonary vasodilation by imatinib and sildenafil. Our results suggest a new paradigm in the treatment of PAH, using an i.v./sublingual tissue-penetrating homing peptide to selectively augment pulmonary vascular effects of nonselective drugs without the potentially problematic conjugation process. CAR may be particularly useful as an add-on therapy to selectively enhance the pulmonary vascular efficacy of any ongoing drug treatment in patients with PAH. PMID:24401613

  12. A novel vascular homing peptide strategy to selectively enhance pulmonary drug efficacy in pulmonary arterial hypertension.

    PubMed

    Toba, Michie; Alzoubi, Abdallah; O'Neill, Kealan; Abe, Kohtaro; Urakami, Takeo; Komatsu, Masanobu; Alvarez, Diego; Järvinen, Tero A H; Mann, David; Ruoslahti, Erkki; McMurtry, Ivan F; Oka, Masahiko

    2014-02-01

    A major limitation in the pharmacological treatment of pulmonary arterial hypertension (PAH) is the lack of pulmonary vascular selectivity. Recent studies have identified a tissue-penetrating homing peptide, CARSKNKDC (CAR), which specifically homes to hypertensive pulmonary arteries but not to normal pulmonary vessels or other tissues. Some tissue-penetrating vascular homing peptides have a unique ability to facilitate transport of co-administered drugs into the targeted cells/tissues without requiring physical conjugation of the drug to the peptide (bystander effect). We tested the hypothesis that co-administered CAR would selectively enhance the pulmonary vascular effects of i.v. vasodilators in Sugen5416/hypoxia/normoxia-exposed PAH rats. Systemically administered CAR was predominantly detected in cells of remodeled pulmonary arteries. Intravenously co-administered CAR enhanced pulmonary, but not systemic, effects of the vasodilators, fasudil and imatinib, in PAH rats. CAR increased lung tissue imatinib concentration in isolated PAH lungs without increasing pulmonary vascular permeability. Sublingual CAR was also effective in selectively enhancing the pulmonary vasodilation by imatinib and sildenafil. Our results suggest a new paradigm in the treatment of PAH, using an i.v./sublingual tissue-penetrating homing peptide to selectively augment pulmonary vascular effects of nonselective drugs without the potentially problematic conjugation process. CAR may be particularly useful as an add-on therapy to selectively enhance the pulmonary vascular efficacy of any ongoing drug treatment in patients with PAH. PMID:24401613

  13. Missed Total Occlusion Due to the Occipital Artery Arising from the Internal Carotid Artery

    SciTech Connect

    Ustunsoz, Bahri Gumus, Burcak; Koksal, Ali; Koroglu, Mert; Akhan, Okan

    2007-02-15

    A 56-year-old man was referred for digital subtraction angiography (DSA) with an ultrasound diagnosis of right proximal internal carotid artery (ICA) stenosis for possible carotid artery stenting. DSA revealed total occlusion of the ICA and an occipital artery arising from the stump and simulating continuation of the ICA. An ascending pharyngeal artery also arose from the same occipital artery. This case is of interest because this is a rare variation besides being a cause of misdiagnosis at carotid ultrasound.

  14. 4-Phenylbutyric Acid Induces Protection against Pulmonary Arterial Hypertension in Rats

    PubMed Central

    Long, Mei; Wang, Jie; Liu, Fen; Gai, Min-Tao; Aierken, Alidan; Li, Ming-Yuan; Li, Qian; Wu, Lei-Qi; Ma, Yi-Tong; Hujiaaihemaiti, Minawaer

    2016-01-01

    Background Endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of various pulmonary diseases via the activation of the unfolded protein response. However, the role of ER stress in pulmonary arterial hypertension (PAH) remains unclear. The well-known chemical chaperone 4-phenylbutyric acid (4-PBA) inhibits ER stress signaling. We hypothesized that known chemical chaperones, including 4-PBA, would inhibit the activation of ER stress and prevent and/or reverse PAH. Methods and Results Male Wistar rats were randomly divided into four groups: a normal control group (NORMAL group), a PAH group, and two PAH model plus 4-PBA treatment groups. The latter two groups included rats receiving 4-PBA by gavage each day as a preventive measure (the PRE group, with PBA starting on the day of PAH induction and continuing for 4 weeks) or as a reversal measure (the REV group, with PBA starting on the third week of PAH induction and continuing for 2 weeks). The PAH model was induced by intraperitoneally administering monocrotaline. The mean pulmonary artery pressure and mean right ventricular pressure were lower in the REV and PRE groups than in the NORMAL group. Furthermore, 4-PBA improved pulmonary arterial remodeling and suppressed the expression of ER stress indicators. Conclusion Our findings indicate that PAH induces ER stress and provokes pulmonary arterial and right ventricular remodeling. Additionally, we show that attenuation of ER stress has the potential to be an effective therapeutic strategy for protecting pulmonary arteries. PMID:27304885

  15. Time Resolved MRA: Evaluation of Intrapulmonary Circulation Parameters in Pulmonary Arterial Hypertension

    PubMed Central

    Jeong, Hyun J.; Vakil, Parmede; Sheehan, John J.; Shah, Sanjiv J.; Cuttica, Michael; Carr, James C.; Carroll, Timothy J.; Davarpanah, Amir

    2010-01-01

    Purpose To determine whether pulmonary arterial and venous transit times measured by time-resolved MRA can be used as a diagnostic tool for pulmonary arterial hypertension (PAH). Materials and Methods 12 patients with confirmed PAH and 10 healthy volunteers were scanned with IRB approval. Time-resolved MRA and 2D phase contrast flow images of the pulmonary vasculature were acquired. Pulmonary arterial and venous transit times (PaTT and PvTT) and pulmonary valve flow (PVF) were obtained. Pulmonary arterial and pulmonary venous blood volumes (PaBV and PvBV) were calculated as the product of flow and transit time. Results Patients with PAH showed statistically significant increases in PaTT and PvTT (p<0.0004, p<0.05 respectively) compared to controls. PaBV (165.2 ± 92.0ml) was significantly higher in PAH subjects than controls (97.0 ± 47.1 ml) (p<0.04), whereas PvBV (127.9 ± 148.9ml) of PAH subjects had no significant increase from those of healthy controls (142.5 ± 104.1 ml) (p<0.38). Conclusion Pulmonary arterial transit times measured using time-resolved MRA can be used as a simple, non-invasive metric for detection of altered hemodynamics in PAH. PMID:21182144

  16. Noninvasive identification of left-sided heart failure in a population suspected of pulmonary arterial hypertension.

    PubMed

    Jacobs, Wouter; Konings, Thelma C; Heymans, Martijn W; Boonstra, Anco; Bogaard, Harm Jan; van Rossum, Albert C; Vonk Noordegraaf, Anton

    2015-08-01

    Exclusion of pulmonary hypertension secondary to left-sided heart disease (left heart failure (LHF)) is pivotal in the diagnosis of pulmonary arterial hypertension (PAH). In case of doubt, invasive measurements are recommended. The aim of the present study was to investigate whether it is possible to diagnose LHF using noninvasive parameters in a population suspected of PAH.300 PAH and 80 LHF patients attended our pulmonary hypertension clinic before August 2010, and were used to build the predictive model. 79 PAH and 55 LHF patients attended our clinic from August 2010, and were used for prospective validation.A medical history of left heart disease, S deflection in V1 plus R deflection in V6 in millimetres on ECG, and left atrial dilation or left valvular heart disease that is worse than mild on echocardiography were independent predictors of LHF. The derived risk score system showed good predictive characteristics: R(2)=0.66 and area under the curve 0.93. In patients with a risk score ≥72, there is 100% certainty that the cause of pulmonary hypertension is LHF. Using this risk score system, the number of right heart catheterisations in LHF may be reduced by 20%.In a population referred under suspicion of PAH, a predictive model incorporating medical history, ECG and echocardiography data can diagnose LHF noninvasively in a substantial percentage of cases. PMID:25837029

  17. Biomarkers for Pediatric Pulmonary Arterial Hypertension – A Call to Collaborate

    PubMed Central

    Colvin, Kelley L.; Dufva, Melanie J.; Delaney, Ryan P.; Ivy, D. Dunbar; Stenmark, Kurt R.; Yeager, Michael E.

    2013-01-01

    Therapeutic approaches in pediatric pulmonary arterial hypertension (PAH) are based primarily on clinician experience, in contrast to the evidence-based approach in adults with pulmonary hypertension. There is a clear and present need for non-invasive and objective biomarkers to guide the accurate diagnosis, treatment, and prognosis of this disease in children. The multifaceted spectrum of disease, clinical presentation, and association with other diseases makes this a formidable challenge. However, as more progress is being made in the understanding and management of adult PAH, the potential to apply this knowledge to children has never been greater. This review explores the state of the art with regard to non-invasive biomarkers in PAH, with an eye toward those adult PAH biomarkers potentially suitable for application in pediatric PAH. PMID:24551834

  18. Effect of the sphingosine kinase 1 selective inhibitor, PF-543 on arterial and cardiac remodelling in a hypoxic model of pulmonary arterial hypertension.

    PubMed

    MacRitchie, Neil; Volpert, Giora; Al Washih, Mohammed; Watson, David G; Futerman, Anthony H; Kennedy, Simon; Pyne, Susan; Pyne, Nigel J

    2016-08-01

    Recent studies have demonstrated that the expression of sphingosine kinase 1, the enzyme that catalyses formation of the bioactive lipid, sphingosine 1-phosphate, is increased in lungs from patients with pulmonary arterial hypertension. In addition, Sk1(-/-) mice are protected from hypoxic-induced pulmonary arterial hypertension. Therefore, we assessed the effect of the sphingosine kinase 1 selective inhibitor, PF-543 and a sphingosine kinase 1/ceramide synthase inhibitor, RB-005 on pulmonary and cardiac remodelling in a mouse hypoxic model of pulmonary arterial hypertension. Administration of the potent sphingosine kinase 1 inhibitor, PF-543 in a mouse hypoxic model of pulmonary hypertension had no effect on vascular remodelling but reduced right ventricular hypertrophy. The latter was associated with a significant reduction in cardiomyocyte death. The protection involves a reduction in the expression of p53 (that promotes cardiomyocyte death) and an increase in the expression of anti-oxidant nuclear factor (erythroid-derived 2)-like 2 (Nrf-2). In contrast, RB-005 lacked effects on right ventricular hypertrophy, suggesting that sphingosine kinase 1 inhibition might be nullified by concurrent inhibition of ceramide synthase. Therefore, our findings with PF-543 suggest an important role for sphingosine kinase 1 in the development of hypertrophy in pulmonary arterial hypertension. PMID:27063355

  19. Pharmacokinetic interactions among imatinib, bosentan and sildenafil, and their clinical implications in severe pulmonary arterial hypertension

    PubMed Central

    Renard, Didier; Bouillon, Thomas; Zhou, Ping; Flesch, Gerard; Quinn, Debbie

    2015-01-01

    Aims This study characterized the population pharmacokinetics (PK) of imatinib in patients with severe pulmonary arterial hypertension (PAH), investigated drug–drug interactions (DDI) among imatinib, sildenafil and bosentan, and evaluated their clinical implications. Methods Plasma concentrations of imatinib, bosentan and sildenafil were collected in a phase III study and were used to characterize the PK of imatinib in this population. DDIs among the three drugs were quantified using a linear mixed model and log-transformed drug concentrations. Results The population mean estimates of apparent clearance (CL/F) and volume (V/F) were 10.8 l h–1 (95% CI 9.2, 12.4 l h–1) and 267 l (95% CI 208, 326 l), respectively. It was estimated that sildenafil concentrations increased, on average, by 64% (95% CI 32%, 103%) and bosentan concentrations by 51% (95% CI 12%, 104%), in the presence of imatinib. Despite increased concentrations of co-medications, treatment differences between imatinib and placebo for change in 6 min walk distance and pulmonary vascular resistance were relatively constant across the entire concentration range for sildenafil and bosentan. Overall, higher concentrations of imatinib and bosentan were not associated with increasing liver enzymes (serum glutamic oxaloacetic transaminases [SGOT]/serum glutamic-pyruvic transaminase [SGPT]). Conclusions Population PKs of imatinib in patients with severe PAH were found comparable with those of patients with chronic myeloid leukemia. Imatinib was found effective regardless of the co-medications and showed intrinsic efficacy beyond merely elevating the concentrations of the co-medications due to DDIs. There was no evidence of increased risk of liver toxicity upon co-administration with bosentan. PMID:25581063

  20. Protein Changes Contributing to Right Ventricular Cardiomyocyte Diastolic Dysfunction in Pulmonary Arterial Hypertension

    PubMed Central

    Rain, Silvia; Bos, Denielli da Silva Goncalves; Handoko, M. Louis; Westerhof, Nico; Stienen, Ger; Ottenheijm, Coen; Goebel, Max; Dorfmüller, Peter; Guignabert, Christophe; Humbert, Marc; Bogaard, Harm‐Jan; dos Remedios, Cris; Saripalli, Chandra; Hidalgo, Carlos G.; Granzier, Henk L.; Vonk‐Noordegraaf, Anton; van der Velden, Jolanda; de Man, Frances S.

    2014-01-01

    Background Right ventricular (RV) diastolic function is impaired in patients with pulmonary arterial hypertension (PAH). Our previous study showed that elevated cardiomyocyte stiffness and myofilament Ca2+ sensitivity underlie diastolic dysfunction in PAH. This study investigates protein modifications contributing to cellular diastolic dysfunction in PAH. Methods and Results RV samples from PAH patients undergoing heart‐lung transplantation were compared to non‐failing donors (Don). Titin stiffness contribution to RV diastolic dysfunction was determined by Western‐blot analyses using antibodies to protein‐kinase‐A (PKA), Cα (PKCα) and Ca2+/calmoduling‐dependent‐kinase (CamKIIδ) titin and phospholamban (PLN) phosphorylation sites: N2B (Ser469), PEVK (Ser170 and Ser26), and PLN (Thr17), respectively. PKA and PKCα sites were significantly less phosphorylated in PAH compared with donors (P<0.0001). To test the functional relevance of PKA‐, PKCα‐, and CamKIIδ‐mediated titin phosphorylation, we measured the stiffness of single RV cardiomyocytes before and after kinase incubation. PKA significantly decreased PAH RV cardiomyocyte diastolic stiffness, PKCα further increased stiffness while CamKIIδ had no major effect. CamKIIδ activation was determined indirectly by measuring PLN Thr17phosphorylation level. No significant changes were found between the groups. Myofilament Ca2+ sensitivity is mediated by sarcomeric troponin I (cTnI) phosphorylation. We observed increased unphosphorylated cTnI in PAH compared with donors (P<0.05) and reduced PKA‐mediated cTnI phosphorylation (Ser22/23) (P<0.001). Finally, alterations in Ca2+‐handling proteins contribute to RV diastolic dysfunction due to insufficient diastolic Ca2+ clearance. PAH SERCA2a levels and PLN phosphorylation were significantly reduced compared with donors (P<0.05). Conclusions Increased titin stiffness, reduced cTnI phosphorylation, and altered levels of phosphorylation of Ca2

  1. Contrast stress echocardiography in hypertensive heart disease

    PubMed Central

    2011-01-01

    Hypertension is associated with atherosclerosis and cardiac and vascular structural and functional changes. Myocardial ischemia may arise in hypertension independent of coronary artery disease through an interaction between several pathophysiological mechanisms, including left ventricular hypertrophy, increased arterial stiffness and reduced coronary flow reserve associated with microvascular disease and endothelial dysfunction. The present case report demonstrates how contrast stress echocardiography can be used to diagnose myocardial ischemia in a hypertensive patient with angina pectoris but without significant obstructive coronary artery disease. The myocardial ischemia was due to severe resistant hypertension complicated with concentric left ventricular hypertrophy and increased arterial stiffness. PMID:22093163

  2. Impact of Whole Body Cryotherapy at -110 °C on Subjects with Arterial Hypertension.

    PubMed

    Missmann, M; Himsl, M; Mur, E; Ulmer, H; Marschang, P

    2016-02-01

    Whole body cryotherapy (WBC) in a cryo-chamber as a medical treatment was first established in Japan in the 1980s, later in Central Europe, and is now becoming more popular also in the United States. The exposure to extreme, non-physiological environmental conditions in a cryo-chamber at -110 °C may exceed the normal adaption capacity. The aim of this study was to investigate the effects of WBC on blood pressure (BP) readings in adult subjects with rheumatic disorders and normal or moderately elevated BP. A sample of 23 subjects (8 female, 15 male) which were recruited according to their pathology between the age of 35 and 69 years undergoing 21 WBC applications was divided into three groups: a group of subjects with anti-hypertensive therapy, a group of subjects with mild arterial hypertension without medical treatment, and a normotensive control-group. A total of 483 BP readings were taken immediately before and after each WBC application. The systolic and diastolic BP were recorded, and the mean arterial pressure, and the amplitude of BP were calculated. A statistically significant rise of BP after WBC was found in the whole sample and in the normotensive group. Over the course of time, no significant change of BP behavior was observed, except for normotensive subjects, who showed a wider range in their systolic BP values. Generally accepted exclusion criteria were applied, and in our sample group WBC was safe with respect to unwanted BP alterations for adult subjects under 70 years-regardless of a pre-existing untreated mild or pharmacologically treated arterial hypertension. Greater changes of BP values might infrequently occur, so an individual monitoring of subjects is necessary. PMID:26408646

  3. Interleukin 13– and interleukin 17A–induced pulmonary hypertension phenotype due to inhalation of antigen and fine particles from air pollution

    PubMed Central

    Park, Sung-Hyun; Chen, Wen-Chi; Esmaeil, Nafiseh; Lucas, Benjamin; Marsh, Leigh M.; Reibman, Joan

    2014-01-01

    Abstract Pulmonary hypertension has a marked detrimental effect on quality of life and life expectancy. In a mouse model of antigen-induced pulmonary arterial remodeling, we have recently shown that coexposure to urban ambient particulate matter (PM) significantly increased the thickening of the pulmonary arteries and also resulted in significantly increased right ventricular systolic pressures. Here we interrogate the mechanism and show that combined neutralization of interleukin 13 (IL-13) and IL-17A significantly ameliorated the increase in right ventricular systolic pressure, the circumferential muscularization of pulmonary arteries, and the molecular change in the right ventricle. Surprisingly, our data revealed a protective role of IL-17A for the antigen- and PM-induced severe thickening of pulmonary arteries. This protection was due to the inhibition of the effects of IL-13, which drove this response, and the expression of metalloelastase and resistin-like molecule α. However, the latter was redundant for the arterial thickening response. Anti-IL-13 exacerbated airway neutrophilia, which was due to a resulting excess effect of IL-17A, confirming concurrent cross inhibition of IL-13- and IL-17A-dependent responses in the lungs of animals exposed to antigen and PM. Our experiments also identified IL-13/IL-17A-independent molecular reprogramming in the lungs induced by exposure to antigen and PM, which indicates a risk for arterial remodeling and protection from arterial constriction. Our study points to IL-13- and IL-17A-coinduced inflammation as a new template for biomarkers and therapeutic targeting for the management of immune response–induced pulmonary hypertension. PMID:25610601

  4. Linked opening angle and histological and mechanical aspects of the proximal pulmonary arteries of healthy and pulmonary hypertensive rats and calves.

    PubMed

    Tian, Lian; Lammers, Steven R; Kao, Philip H; Reusser, Mark; Stenmark, Kurt R; Hunter, Kendall S; Qi, H Jerry; Shandas, Robin

    2011-11-01

    Understanding how arterial remodeling changes the mechanical behavior of pulmonary arteries (PAs) is important to the evaluation of pulmonary vascular function. Early and current efforts have focused on the arteries' histological changes, their mechanical properties under in vitro mechanical testing, and their zero-stress and no-load states. However, the linkage between the histology and mechanical behavior is still not well understood. To explore this linkage, we investigated the geometry, residual stretch, and histology of proximal PAs in both adult rat and neonatal calf hypoxic models of pulmonary hypertension (PH), compared their changes due to chronic hypoxia across species, and proposed a two-layer mechanical model of artery to relate the opening angle to the stiffness ratio of the PA outer to inner layer. We found that the proximal PA remodeling in calves was quite different from that in rats. In rats, the arterial wall thickness, inner diameter, and outer layer thickness fraction all increased dramatically in PH and the opening angle decreased significantly, whereas in calves, only the arterial wall thickness increased in PH. The proposed model predicted that the stiffness ratio of the calf proximal PAs changed very little from control to hypertensive group, while the decrease of opening angle in rat proximal PAs in response to chronic hypoxia was approximately linear to the increase of the stiffness ratio. We conclude that the arterial remodeling in rat and calf proximal PAs is different and the change of opening angle can be linked to the change of the arterial histological structure and mechanics. PMID:21856906

  5. Where do we go from here? Reappraising the data on anticoagulation in pulmonary arterial hypertension

    PubMed Central

    Cirulis, Meghan M.

    2016-01-01

    The use of anticoagulation as part of the treatment regimen in pulmonary arterial hypertension (PAH) remains a topic of debate. A recently published analysis of anticoagulation use in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) study offers conflicting conclusions regarding the benefit of this therapeutic strategy. There remains no robust randomized trial in PAH weighing the risks versus benefits of including anticoagulation in treatment regimens, leaving clinicians to surmise value in individual patients. Reexamination of available data may help to provide guidance on this controversial topic in the absence of future dedicated investigations. PMID:27162687

  6. Respiratory and limb muscle dysfunction in pulmonary arterial hypertension: a role for exercise training?

    PubMed Central

    2015-01-01

    Abstract Respiratory and limb muscle dysfunction is emerging as an important pathophysiological abnormality in pulmonary arterial hypertension (PAH). Muscle abnormalities appear to occur frequently and promote dyspnea, fatigue, and exercise limitation in patients with PAH. Preliminary data suggest that targeted muscle training may be of benefit, although further evidence is required to consolidate these findings into specific recommendations for exercise training in patients with PAH. This article reviews the current evidence on prevalence, risk factors, and implications of respiratory and limb muscle dysfunction in patients with PAH. It also reviews the impact of exercise rehabilitation on morphologic, metabolic, and functional muscle profile and outcomes in PAH. Future research priorities are highlighted. PMID:26401245

  7. Lipid X ameliorates pulmonary hypertension and protects sheep from death due to endotoxin.

    PubMed Central

    Golenbock, D T; Will, J A; Raetz, C R; Proctor, R A

    1987-01-01

    Lipid X (2,3-diacylglucosamine-1-phosphate) is a novel monosaccharide precursor of lipid A that has some of the physiologic activities of endotoxin but little toxicity. To determine whether lipid X would interfere with the toxic effects of endotoxin, we pretreated sheep with either 100 or 200 micrograms of lipid X per kg of body weight and then challenged them with a potentially fatal dose of Escherichia coli endotoxin (20 micrograms/kg). Twenty-one sheep underwent pulmonary artery catheterization and were monitored for changes in pulmonary artery pressure, temperature, pH, partial O2 pressure, partial CO2 pressure, blood pressure, and cell counts over 7 h. Overall mortality for control animals was 37% versus 5.3% for pretreated animals. None of the 13 animals pretreated with 100 micrograms of lipid X per kg died. These differences in survival were significant (P less than 0.05). Animals pretreated with 100 micrograms of lipid X per kg had significantly lower pulmonary artery pressure during both phases 1 and 2 of endotoxin-induced pulmonary artery hypertension. A higher dose of lipid X, 200 micrograms/kg, produced pulmonary hypertension. Perhaps because lipid X is a subunit of lipid A, lipid X shows a partial pyrogenic effect while also decreasing the pyrogenic activity of complete lipopolysaccharide (LPS). Lipid X did not prevent endotoxin-induced neutropenia or moderate hypotension in response to LPS. Lipid X is a potential prototype compound for a new type of chemotherapy directed at blocking the harmful effects of LPS during bacterial septicemia. PMID:3308707

  8. Serum Bilirubin Is Inversely Associated with Increased Arterial Stiffness in Men with Pre-Hypertension but Not Normotension

    PubMed Central

    Huang, Yao-Hsien; Yang, Yi-Ching; Lu, Feng-Hwa; Sun, Zih-Jie; Wu, Jin-Shang; Chang, Chih-Jen

    2016-01-01

    Objective Serum bilirubin level has shown to be inversely associated with coronary atherosclerosis, and may serve as a protective biomarker of coronary artery disease. Serum bilirubin has also been shown to be negatively associated with brachial-ankle pulse wave velocity (baPWV) in men without a history of hypertension, and in men with hypertension. It is unknown whether such associations can be observed in the pre-hypertensive or normotensive population. This study thus aimed to investigate the relationship between serum bilirubin level and increased arterial stiffness in subjects with pre-hypertension and normotension for both genders. Methods A cross-sectional sample of 3,399 apparently healthy subjects undergoing a medical check-up at National Cheng Kung University Hospital was enrolled between October 2006 and August 2009, after excluding subjects with serum total bilirubin level greater than 20.52 μmol/L. Increased arterial stiffness was defined as baPWV of 1,400 cm/s or higher as the dichotomous variable and bilirubin as the continuous variable. Results Based on multiple linear regression analysis, serum bilirubin level was inversely associated with baPWV in non-hypertensive men (β = -0.066, p < 0.001) but not in non-hypertensive women. In addition, the inverse relationship between bilirubin level and baPWV was found statistically significant only in pre-hypertensive men (β = -0.110, p < 0.001). Multiple logistic regression analysis showed that serum bilirubin was inversely associated with increased arterial stiffness in men with pre-hypertension (odds ratio = 0.955, 95% confidence interval = 0.916–0.996, p < 0.05) but not normotension after adjustment for other confounding factors. However, the relationship between total bilirubin level and increased arterial stiffness did not reach statistical significance for female subjects with pre-hypertension and normotension. Conclusion Serum bilirubin is inversely associated with increased arterial stiffness in

  9. Residual small artery impairment in hypertensive patients with normal albumin-creatinine ratio.

    PubMed

    Eftekhari, Ashkan; Wiggers, Signe Nielsen; Mathiassen, Ole Norling; Christensen, Kent Lodberg

    2016-06-01

    Objectives Previous studies have suggested that urine albumin excretion (UAE) mirrors generalized vascular damage; however, it is unclear to which degree UAE mirrors small artery impairment. Design We enrolled 67 patients with uncomplicated essential hypertension (EH) during stable antihypertensive therapy. F-Rmin, ACR on three non-consecutive morning urine samples, pulse wave velocity (PWV), and 24-h ambulatory blood pressure (ABPM) were measured. Results ACR was low (0.39 and 0.30-0.60), but abnormal small artery structure defined as F-Rmin > mean + 2 standard deviations of normotensive value (1.99 + 1 mmHg min/(ml/100 ml)) was present in 45% (n = 30). The mean F-Rmin was 2.89 ± 0.09 mmHg min/(ml/100 ml). ACR correlated significantly to PWV (r(2 )=( )0.11; p < 0.05) and pulse pressure (r(2 )=( )0.15; p < 0.001), but not F-Rmin and (r(2 )=( )0.05, p = 0.07). Conclusions Abnormal microvascular structure was present even in EH patients with low UAE. ACR correlated to arterial stiffness and not to small artery structure; therefore, UEA did not reflect microvascular damage in this population. ACR and F-Rmin thus reflect two distinct types of subclinical organ damage in hypertension. PMID:26856990

  10. Calcilytics enhance sildenafil-induced antiproliferation in idiopathic pulmonary arterial hypertension.

    PubMed

    Yamamura, Aya; Yagi, Satomi; Ohara, Naoki; Tsukamoto, Kikuo

    2016-08-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and fatal disease of the pulmonary artery resulting from currently unidentified etiology. IPAH is pathologically characterized as sustained vasoconstriction and vascular remodeling of the pulmonary artery. Phosphodiesterase type 5 (PDE5) inhibitors have been clinically used in the treatment of IPAH. Recently, we have shown that Ca(2+)-sensing receptor (CaSR) antagonists, or calcilytics, inhibit excessive cell proliferation of pulmonary arterial smooth muscle cells (PASMCs) from IPAH patients. In this study, the additive or synergistic effect of calcilytics on antiproliferation following PDE5 inhibition was examined in IPAH-PASMCs by MTT assay. Treatment with sildenafil blocked the excessive cell proliferation of IPAH-PASMCs in a concentration-dependent manner with an IC50 value of 16.9μM. However, sildenafil (0.03-100μM) did not affect the cell growth of PASMCs from normal subjects and patients with chronic thromboembolic pulmonary hypertension (CTEPH). Co-treatment with 0.3μM NPS2143, a calcilytic, additively enhanced the antiproliferative effect induced by sildenafil (3 or 30μM) in IPAH-PASMCs. Additionally, the inhibitory effect of calcilytics, NPS2143 or Calhex 231 (1 or 10μM), on excessive cell proliferation of IPAH-PASMCs was synergistic increased in the presence of 1μM sildenafil. Similar results were obtained by BrdU incorporation assay. These findings reveal that calcilytics additively/synergistically enhance the antiproliferative activity mediated by PDE5 inhibition, suggesting that a combination therapy of a PDE5 inhibitor with a calcilytic may be useful as a novel therapeutic approach for IPAH. PMID:27164419

  11. Hypertensive emergency due to pheochromocytoma crisis complicated with refractory hemodynamic collapse.

    PubMed

    Hayıroğlu, Mert İlker; Yıldırımtürk, Özlem; Bozbay, Mehmet; Eren, Mehmet; Pehlivanoğlu, Seçkin

    2015-12-01

    Hypertensive emergency usually appears in older patients with previous recurrent episodes, and is among the most frequent admissions to emergency departments. A 29-year-old woman was referred to our clinic with the diagnosis of hypertensive emergency. The patient complained of severe headache, dyspnea, palpitation, diaphoresis, and confusion due to hypertensive encephalopathy. Her blood pressure was 250/150 mmHg on admission. At the referral hospital, the patient had undergone cranial CT because of her confused state and this excluded acute cerebral hemorrhage. Also at that hospital, thoracoabdominal CT for differential diagnosis depicted an adrenal mass with a necrotic core. After admission to our clinic, initial control of excessive blood pressure was not achieved despite high dose intravenous nitrate therapy. Thereafter intravenous esmolol treatment was initiated simultaneously with oral alpha blocker therapy in order to counterbalance the unopposed alpha adrenergic activity with beta blocker therapy. After 12 hours, sudden onset of hypotension developed and deepened despite IV saline, inotropic and vasopressor agents such as IV dopamine, noradrenaline and adrenaline. The patient died at the 24th hour due to hemodynamic collapse as a result of hyperadrenergic state due to possible pheochromocytoma crisis. This case is an exceptional example of hypertensive emergency secondary to fulminant pheochromocytoma crisis failing to respond to intensive antihypertensive treatment, and in which patient death was unavoidable due to uncontrolled excessive adrenergic activity which led to profound cardiogenic shock. PMID:26717337

  12. Bilateral Common Carotid Artery Occlusion in Spontaneously Hypertensive Rats: A Feasible Animal Model for Ocular Ischemic Syndrome.

    PubMed

    Wang, Yacong; Fan, Yuhua; Zhang, Lihong; Wang, Yi-Xiang J; Qi, Wei; Liang, Willmann; Wang, Chunmei; T W Yew, David; Ye, Cunxi; Sha, Ou

    2016-06-01

    The purpose of this study was to investigate the feasibility of inducing ocular ischemic syndrome in spontaneously hypertensive rats. Hypertensive and normotensive Wistar-Kyoto rats had bilateral occlusion or sham surgery. They were divided into 4 groups: (1) hypertensive-ischemia, (2) hypertensive-sham, (3) normotensive-ischemia, and (4) normotensive-sham. Four months after the operation, the global changes of the eye and pupillary light reflex were assessed. Then each rat was perfused, and randomly one of the bulbuses oculi was prepared as retinal flat mounts for investigation of vascular changes. The opposite eyeball was prepared as a paraffin section for observation of the linear density of retinal ganglion cells and for thickness measurement. One hypertensive-ischemia rat had a cataract in one eye and another rat in the same group had bulbus oculi collapse in one eye. The light reflex disappeared in 13.33% of hypertensive-ischemia rats, and the rest of the hypertensive-ischemia rats and normotensive-ischemia rats had slow reflex. Compared with the respective controls, the peripheral retinal vascular network in hypertensive-ischemia and normotensive-ischemia rats was sparse; linear density of the retinal ganglion cells was significantly reduced; and the retinal thickness was reduced. Compared with normotensive-ischemia rats, the hypertensive-ischemia rats demonstrated more severe changes. After bilateral common carotic artery occlusion, the eyes of hypertensive rats developed various pathological changes similar to those of ocular ischemic syndrome. In conclusion, an animal model for ocular ischemic syndrome can be created by bilateral common carotid artery occlusion in spontaneously hypertensive rats. Anat Rec, 299:806-814, 2016. © 2016 Wiley Periodicals, Inc. PMID:26917224

  13. The relationship between occupational exposure to lead and manifestation of cardiovascular complications in persons with arterial hypertension

    SciTech Connect

    Poreba, Rafal; Gac, Pawel; Poreba, Malgorzata; Andrzejak, Ryszard

    2010-11-15

    The chronic exposure to lead represents a risk factor of arterial hypertension development. Ambulatory blood pressure monitoring is the most prognostically reliable method of measuring of arterial blood pressure. The study is aimed at evaluating the relationship between occupational exposure to lead and manifestation of cardiovascular complications in patients with arterial hypertension. The studies included 73 men (mean age, 54.26 {+-} 8.17 years) with arterial hypertension, treated with hypotensive drugs: group I-persons occupationally exposed to lead (n = 35) and group II-individuals not exposed to lead (n = 38). An analysis of results obtained during ambulatory blood pressure monitoring disclosed significantly higher values of mean systolic blood pressure, mean blood pressure, pulse pressure, and variability of systolic blood pressure in the group of hypertensive patients occupationally exposed to lead as compared to patients with arterial hypertension but not exposed to lead. The logistic regression showed that a more advanced age, higher concentration of blood zinc protoporphyrin, and a higher mean value of pulse pressure represented independent risk factors of left ventricular hypertrophy in the group of persons with arterial hypertension and chronically exposed to lead (OR{sub age} = 1.11; OR{sub ZnPP} = 1.32; OR{sub PP} = 1,43; p < 0.05). In view of the above data demonstration that occupational exposure to lead represents an independent risk factor of increased pulse pressure may be of key importance in the process of shaping general social awareness as to harmful effects of lead compounds on human health.

  14. Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability

    PubMed Central

    Champion, Hunter C.; Campbell-Lee, Sally A.; Bivalacqua, Trinity J.; Manci, Elizabeth A.; Diwan, Bhalchandra A.; Schimel, Daniel M.; Cochard, Audrey E.; Wang, Xunde; Schechter, Alan N.; Noguchi, Constance T.; Gladwin, Mark T.

    2007-01-01

    Pulmonary hypertension is a highly prevalent complication of sickle cell disease and is a strong risk factor for early mortality. However, the pathophysiologic mechanisms leading to pulmonary vasculopathy remain unclear. Transgenic mice provide opportunities for mechanistic studies of vascular pathophysiology in an animal model. By microcardiac catheterization, all mice expressing exclusively human sickle hemoglobin had pulmonary hypertension, profound pulmonary and systemic endothelial dysfunction, and vascular instability characterized by diminished responses to authentic nitric oxide (NO), NO donors, and endothelium-dependent vasodilators and enhanced responses to vasoconstrictors. However, endothelium-independent vasodilation in sickle mice was normal. Mechanisms of vasculopathy in sickle mice involve global dysregulation of the NO axis: impaired constitutive nitric oxide synthase activity (NOS) with loss of endothelial NOS (eNOS) dimerization, increased NO scavenging by plasma hemoglobin and superoxide, increased arginase activity, and depleted intravascular nitrite reserves. Light microscopy and computed tomography revealed no plexogenic arterial remodeling or thrombi/emboli. Transplanting sickle marrow into wild-type mice conferred the same phenotype, and similar pathobiology was observed in a nonsickle mouse model of acute alloimmune hemolysis. Although the time course is shorter than typical pulmonary hypertension in human sickle cell disease, these results demonstrate that hemolytic anemia is sufficient to produce endothelial dysfunction and global dysregulation of NO. PMID:17158223

  15. Prevalence of arterial hypertension among Brazilian adolescents: systematic review and meta-analysis

    PubMed Central

    2013-01-01

    the small number of studies in some regions of Brazil, the pooled prevalence found in both males and females shows that systemic arterial hypertension should be monitored in the population aged 10–20 years and that specific measures are required to prevent and control the disease, as well as its risk factors. Studies that compare regional heterogeneities may contribute to the knowledge of factors associated with increased blood pressure among adolescents. PMID:24025095

  16. Micro-CT image-derived metrics quantify arterial wall distensibility reduction in a rat model of pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Johnson, Roger H.; Karau, Kelly L.; Molthen, Robert C.; Haworth, Steven T.; Dawson, Christopher A.

    2000-04-01

    We developed methods to quantify arterial structural and mechanical properties in excised rat lungs and applied them to investigate the distensibility decrease accompanying chronic hypoxia-induced pulmonary hypertension. Lungs of control and hypertensive (three weeks 11% O2) animals were excised and a contrast agent introduced before micro-CT imaging with a special purpose scanner. For each lung, four 3D image data sets were obtained, each at a different intra-arterial contrast agent pressure. Vessel segment diameters and lengths were measured at all levels in the arterial tree hierarchy, and these data used to generate features sensitive to distensibility changes. Results indicate that measurements obtained from 3D micro-CT images can be used to quantify vessel biomechanical properties in this rat model of pulmonary hypertension and that distensibility is reduced by exposure to chronic hypoxia. Mechanical properties can be assessed in a localized fashion and quantified in a spatially-resolved way or as a single parameter describing the tree as a whole. Micro-CT is a nondestructive way to rapidly assess structural and mechanical properties of arteries in small animal organs maintained in a physiological state. Quantitative features measured by this method may provide valuable insights into the mechanisms causing the elevated pressures in pulmonary hypertension of differing etiologies and should become increasingly valuable tools in the study of complex phenotypes in small-animal models of important diseases such as hypertension.

  17. Peptide-micelle hybrids containing fasudil for targeted delivery to the pulmonary arteries and arterioles to treat pulmonary arterial hypertension.

    PubMed

    Gupta, Nilesh; Ibrahim, Hany M; Ahsan, Fakhrul

    2014-11-01

    This study investigates the respirability and efficacy of peptide-micelle hybrid nanoparticles as carriers for inhalational therapy of pulmonary arterial hypertension (PAH). CARSKNKDC (CAR), a cell-penetrating and lung-homing peptide, conjugated polyethylene glycol-distearoyl-phosphoethanolamine micelles containing fasudil, an investigational anti-PAH drug, were prepared by solvent evaporation method and characterized for various physicochemical properties. The pharmacokinetics and pharmacological efficacy of hybrid particles containing fasudil were evaluated in healthy rats and monocrotaline-induced PAH rats. CAR micelles containing fasudil had an entrapment efficiency of approximately 58%, showed controlled release of the drug, and were monodispersed with an average size of approximately 14 nm. Nuclear magnetic resonance scan confirmed the drug's presence in the core of peptide-micelle hybrid particles. Compared with plain micelles, CAR peptide increased the cellular uptake by approximately 1.7-fold and extended the drug half-life by approximately fivefold. The formulations were more prone to accumulate in the pulmonary vasculature than in the peripheral blood, which is evident from the ratio of the extent of reduction of pulmonary and systemic arterial pressures. On the whole, this study demonstrates that peptide-polymer hybrid micelles can serve as inhalational carriers for PAH therapy. PMID:25266507

  18. Vasovagal response secondary to permanent contraception device in pulmonary arterial hypertension

    PubMed Central

    Cope, Jessica; Alnuaimat, Hassan

    2015-01-01

    Abstract Adequate contraception is an essential component of managing pulmonary hypertension in women of childbearing age. Intrauterine devices are a popular contraceptive choice for many women but are associated with a risk of vagal response upon placement in certain patients with pulmonary hypertension, which may not be well tolerated. More recently, newer permanent contraception devices have emerged in the market, such as the Essure. We describe the first case, to our knowledge, of vagal-associated response due to an Essure device placement. PMID:26697184

  19. Arterial microanatomy determines the success of energy-based renal denervation in controlling hypertension

    PubMed Central

    Tzafriri, Abraham R.; Keating, John H.; Markham, Peter M.; Spognardi, Anna-Maria; Stanley, James R. L.; Wong, Gee; Zani, Brett G.; Grunewald, Debby; O’Fallon, Patrick; Fuimaono, Kristine; Mahfoud, Felix; Edelman, Elazer R.

    2015-01-01

    Renal Denervation (RDN) is a treatment option for patients with hypertension resistant to conventional therapy. Clinical trials have demonstrated variable benefit. To understand the determinants of successful clinical response to this treatment, we integrated porcine and computational models of intravascular radiofrequency RDN. Controlled single-electrode denervation resulted in ablation zone geometries that varied in arc, area and depth, depending on the composition of the adjacent tissue substructure. Computational simulations predicted that delivered power density was influenced by tissue substructure, and peaked at the conductivity discontinuities between soft fatty adventitia and water rich tissues (media, lymph nodes etc.), not at the electrode-tissue interface). Electrode irrigation protected arterial wall tissue adjacent to the electrode by clearing heat that diffuses from within the tissue, without altering peri-arterial ablation. Seven days after multi-electrode treatments, renal norepinephrine and blood pressure were reduced. Blood pressure reductions were correlated with the size-weighted number of degenerative nerves, implying that the effectiveness of the treatment in decreasing hypertension depends on the extent of nerve injury and ablation, which in turn are determined by the tissue microanatomy at the electrode site. These results may explain the variable patient response to RDN and suggest a path to more robust outcomes. PMID:25925684

  20. Quinapril decreases antifibrinolytic and prooxidative potential of propofol in arterial thrombosis in hypertensive rats.

    PubMed

    Wojewodzka-Zelezniakowicz, Marzena; Kisiel, Wioleta; Kramkowski, Karol; Gromotowicz-Poplawska, Anna; Zakrzeska, Agnieszka; Stankiewicz, Adrian; Kolodziejczyk, Patrycjusz; Szemraj, Janusz; Ladny, Jerzy Robert; Chabielska, Ewa

    2016-04-01

    Angiotensin converting enzyme inhibitors and propofol both exert hypotensive action and may affect hemostasis. We investigated the influence of quinapril and propofol on hemodynamics and hemostasis in renal-hypertensive rats with induced arterial thrombosis. Two-kidney, one clip hypertensive rats were treated with quinapril (3.0 mg/kg for 10 days), and then received propofol infusion (15 mg/kg/h) during ongoing arterial thrombosis. The hemodynamic and hemostatic parameters were assayed. Quinapril exerted a hypotensive effect increasing after propofol infusion. Quinapril showed an antithrombotic effect with the platelet adhesion reduction, fibrinolysis enhancement and oxidative stress reduction. Propofol did not influence thrombosis; however, it inhibited fibrinolysis and showed prooxidative action. The effect of propofol on fibrinolysis and oxidative stress was significantly lower in quinapril-pretreated rats. Mortality was increased among rats treated with both drugs together. Our study demonstrates that pretreatment with quinapril reduced the adverse effects of propofol on hemostasis. Unfortunately, co-administration of both drugs potentiated hypotension in rats, which corresponds to higher mortality. PMID:27169890

  1. Thrombospondin-4 knockout in hypertension protects small-artery endothelial function but induces aortic aneurysms.

    PubMed

    Palao, Teresa; Rippe, Catarina; van Veen, Henk; VanBavel, Ed; Swärd, Karl; Bakker, Erik N T P

    2016-06-01

    Thrombospondin-4 (TSP-4) is a multidomain calcium-binding protein that has both intracellular and extracellular functions. As an extracellular matrix protein, it is involved in remodeling processes. Previous work showed that, in the cardiovascular system, TSP-4 expression is induced in the heart in response to experimental pressure overload and infarction injury. Intracellularly, it mediates the endoplasmic reticulum stress response in the heart. In this study, we explored the role of TSP-4 in hypertension. For this purpose, wild-type and TSP-4 knockout (Thbs4(-/-)) mice were treated with angiotensin II (ANG II). Hearts from ANG II-treated Thbs4(-/-) mice showed an exaggerated hypertrophic response. Interestingly, aortas from Thbs4(-/-) mice treated with ANG II showed a high incidence of aneurysms. In resistance arteries, ANG II-treated wild-type mice showed impaired endothelial-dependent relaxation. This was not observed in ANG II-treated Thbs4(-/-) mice or in untreated controls. No differences were found in the passive pressure-diameter curves or stress-strain relationships, although ANG II-treated Thbs4(-/-) mice showed a tendency to be less stiff, associated with thicker diameters of the collagen fibers as revealed by electron microscopy. We conclude that TSP-4 plays a role in hypertension, affecting cardiac hypertrophy, aortic aneurysm formation, as well as endothelial-dependent relaxation in resistance arteries. PMID:26968543

  2. A study of aspirin and clopidogrel in idiopathic pulmonary arterial hypertension.

    PubMed

    Robbins, I M; Kawut, S M; Yung, D; Reilly, M P; Lloyd, W; Cunningham, G; Loscalzo, J; Kimmel, S E; Christman, B W; Barst, R J

    2006-03-01

    Idiopathic pulmonary arterial hypertension (IPAH) is characterised by in situ thrombosis and increased thromboxane (Tx) A2 synthesis; however, there are no studies of antiplatelet therapy in IPAH. The aim of the current study was to determine the biochemical effects of aspirin (ASA) and clopidogrel on platelet function and eicosanoid metabolism in patients with IPAH. A randomised, double-blind, placebo-controlled crossover study of ASA 81 mg once daily and clopidogrel 75 mg once daily was performed. Plasma P-selectin levels and aggregometry were measured after exposure to adenosine diphosphate, arachidonic acid and collagen. Serum levels of TxB2 and urinary metabolites of TxA2 and prostaglandin I2 (Tx-M and PGI-M, respectively) were assessed. A total of 19 IPAH patients were enrolled, of whom nine were being treated with continuous intravenous epoprostenol. ASA and clopidogrel significantly reduced platelet aggregation to arachidonic acid and adenosine diphosphate, respectively. ASA significantly decreased serum TxB2, urinary Tx-M levels and the Tx-M/PGI-M ratio, whereas clopidogrel had no effect on eicosanoid levels. Neither drug significantly lowered plasma P-selectin levels. Epoprostenol use did not affect the results. In conclusion, aspirin and clopidogrel inhibited platelet aggregation, and aspirin reduced thromboxane metabolite production without affecting prostaglandin I2 metabolite synthesis. Further clinical trials of aspirin in patients with idiopathic pulmonary arterial hypertension should be performed. PMID:16507859

  3. Safety, efficacy, and clinical utility of macitentan in the treatment of pulmonary arterial hypertension

    PubMed Central

    Monaco, Thomas J; Davila, Carlos D

    2016-01-01

    Pulmonary arterial hypertension is a progressive, debilitating disease caused by a dysregulation of the pulmonary vascular tone that inevitably leads to right heart failure and death without treatment. Until relatively recently, the treatment options for those afflicted by pulmonary arterial hypertension were limited; today, a greater understanding of the pathophysiology behind this disease has led to several evidence-based therapies that can improve pulmonary function and quality of life for these patients. One of the primary mediators of pulmonary vascular tone is endothelin-1, which is a potent and long-lasting vasoconstrictor. Macitentan is a second-generation endothelin receptor antagonist that acts selectively as a pulmonary vasodilator without the significant side effects noted with previous endothelin receptor antagonists. This review focuses on the mechanism of action and pharmacokinetics of macitentan, as well as the adverse effects, efficacy, and clinical uses of macitentan in the clinical trials to date. In addition, the authors briefly review clinical trials currently underway to illustrate possible future directions for the use of macitentan. PMID:27274200

  4. [Features of brain oscillatory activity and cardiac defense in treatment arterial hypertensives].

    PubMed

    Aftanas, L I; Brak, I V; Gilinskaia, O M; Pavlov, S V; Reva, N V

    2014-01-01

    Stress reactivity of the motivational system of defense can be assessed with the aid the cardiac defense response (CDR) - the reaction of the cardiovascular system to unexpected aversive unconditioned stimulus. The main objective of the study was revealing putative contribution of oscillatory systems of the brain into central pathogenic mechanisms of enhanced blood pressure (BP) stress-reactivity in naive patients with arterial hypertension (AH) of the 1st-2nd degrees (n = 17) and healthy control (n = 19) subjects. Using dynamic registration "beat-by-beat" arterial pressure, and oscillatory activity related EEG (64 channels) is estimated using the event-related synchronization/desynchronization (ERD/ERS). Along with abnormally high blood pressure in patients with hypertension background set significantly lower concentrations of serotonin blood platelets and increased tonic activation of the left hemisphere, reflected in the asymmetric reduction of delta- (2-4 Hz) and theta-1 (4-6 Hz) power in the central and parietal cortex in the hemisphere CDR of the patients are characterized by hyperactivity both short- and long-latency components of blood pressure. According to the dynamic analysis of the concomitant EEG, long-latency BP components may be accounted by, among other mechanisms, weakening of the descending ("top-down") inhibitory control, hypothetically implemented with the high-frequency EEG alpha (10-12 Hz) oscillations from the medial central-parietal cortex of both hemispheres of the brain. PMID:25464727

  5. 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension.

    PubMed

    Ding, Yan; Wu, Cheng-Chia; Garcia, Victor; Dimitrova, Irina; Weidenhammer, Adam; Joseph, Gregory; Zhang, Frank; Manthati, Vijay L; Falck, John R; Capdevila, Jorge H; Schwartzman, Michal L

    2013-09-01

    20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented 5α-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14(-/-) mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 ± 1 vs. 15 ± 1 μm) and M/L (0.29 ± 0.03 vs. 0.17 ± 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12-20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 ± 4 vs. 92 ± 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 ± 1 vs. 16 ± 1 μm; M/L: 0.39 ± 0.04 vs. 0.23 ± 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. PMID

  6. 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension

    PubMed Central

    Ding, Yan; Wu, Cheng-Chia; Garcia, Victor; Dimitrova, Irina; Weidenhammer, Adam; Joseph, Gregory; Zhang, Frank; Manthati, Vijay L.; Falck, John R.; Capdevila, Jorge H.

    2013-01-01

    20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented 5α-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14−/− mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 ± 1 vs. 15 ± 1 μm) and M/L (0.29 ± 0.03 vs. 0.17 ± 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12–20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 ± 4 vs. 92 ± 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 ± 1 vs. 16 ± 1 μm; M/L: 0.39 ± 0.04 vs. 0.23 ± 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. PMID

  7. The role of endogenous cardiotonic steroids in pathogenesis of cardiovascular and renal complications of arterial hypertension.

    PubMed

    Paczula, Aneta; Więcek, Andrzej; Piecha, Grzegorz

    2016-01-01

    Endogenous cardiotonic steroids (CTS), also called digitalis-like factors, are a group of steroid hormones linking high salt intake and elevated blood pressure and in part responsible for target organ damage in arterial hypertension. CTS act primarily through their ability to inhibit the ubiquitous transport enzyme sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase). A portion of Na⁺/K⁺-ATPase does not seem to actively "pump" sodium and potassium but is closely associated with other key signaling proteins. Plasma concentration and urine excretion of CTS are increased in experimental models with volume expansion and on a high salt diet. Elevated plasma concentration of marinobufagenin has been shown in volume-expanded states such as essential hypertension, primary aldosteronism, chronic renal failure, congestive heart failure and pregnancy. In experimental models marinobufagenin induces heart and kidney fibrosis to the same extent as observed in uremia. Neutralization of marinobufagenin with antibodies prevents such heart remodeling. Expanding our understanding of this new class of hormones may lead to development of novel and effective therapeutic strategies in hypertensive patients with renal and cardiovascular complications. PMID:27117099

  8. Anticoagulation in patients with pulmonary arterial hypertension: An update on current knowledge.

    PubMed

    Roldan, Tamara; Landzberg, Michael J; Deicicchi, David J; Atay, Julie K; Waxman, Aaron B

    2016-02-01

    Pulmonary hypertension is a severe clinical condition characterized by molecular and anatomic changes in pulmonary circulation. It is associated with increased pulmonary vascular resistance, which leads to right-sided heart failure if left untreated and, ultimately, death. Treatment of patients with pulmonary arterial hypertension (PAH) involves a complex strategy that takes into consideration disease severity, general and supportive measures, and combination drug regimens. Abnormalities of blood coagulation factors, anti-thrombotic factors, and the fibrinolytic system may contribute to a prothrombotic state in patients with idiopathic PAH. These physiologic changes, in concert with the presence of non-specific risk factors for venous thromboembolism such as heart failure and immobility, are thought to be the basis for oral anticoagulation in PAH. Several observational studies provide helpful information in favor of anticoagulation use in idiopathic PAH but not in other pulmonary hypertension etiologies. Guideline recommendations are based on the lack of prospective comparative trials in this regard. For that reason, large differences exist in the use of anticoagulants in different countries and centers. More studies should be carried out to clarify the risks and the potential benefits of anticoagulant use in a heterogeneous population of patients who are already at considerable life risk. PMID:26527532

  9. [Effect of paeonol on blood pressure and blood flow in artery of spontaneously hypertensive rats and its mechanisms related on vasomotion].

    PubMed

    Zhang, Jin-yan; Zhao, Le; Li, Yi-kui; Weng, Wei-liang

    2015-12-01

    Previous studies have shown that paeonol can antagonize acute myocardial ischemia and infarction in rat. This study further researched the effects of paeonol on blood pressure and blood flow in the artery of spontaneously hypertensive rats and its mechanisms related on vasomotion. Firstly, thirty spontaneously hypertensive rats were randomly divided into spontaneously hypertensive control group and paeonol-treating groups of high dose and low dose, and also, the other ten Wistar rats as healthy control group. Before and after the intraduodenal administration of the drug, arterial blood pressure was measured by carotid artery and blood flow through the renal artery and carotid artery in vivo were measured by animal flowmeter. The same volume of solvent was given to the spontaneously hypertensive control group and the healthy control group, and the other operations were same. In order to further study the effect of paeonol on vasomotor function, the superior mesenteric artery, renal artery and coronary artery of the spontaneously hypertensive rat were removed and separated, precontracted by a certain concentration of potassium chloride (KCl) and 5-serotonin (5-HT) respectively, and dilatory responses were assessed by cumulative addition of paeonol. Results showed that after duodenal one-time delivery of paeonol, the blood pressure significantly lowered, the renal arterial blood flow and the carotid arterial blood flow significantly increased in spontaneously hypertensive rat. And also, paeonol relaxed the mesenteric artery, renal artery and the coronary artery of spontaneously hypertensive rat in a concentration-dependent manner. These results indicated that the effect of paeonol on decreasing arterial blood pressure and increasing the arterial blood flow was related to its vasodilative effect. PMID:27245041

  10. Are Transcutaneous O2 and CO2 determinations of value in Pulmonary Arterial Hypertension?

    PubMed Central

    Tonelli, Adriano R.; Alkukhun, Laith; Cikach, Frank; Ahmed, Mostafa; Dweik, Raed A.

    2015-01-01

    Background We hypothesized that transcutaneous gas determinations of O2 and CO2 (TcPO2 and TcPCO2) are associated with the severity of pulmonary arterial hypertension (PAH). Methods In this cross-sectional study we included consecutive patients with PAH (group 1 pulmonary hypertension (PH)) (n=34). Transcutaneous gas determinations were compared to those of age- and gender-matched healthy controls (n=14), non-group 1 PH (n=19) or patients with high estimated right ventricular systolic pressure on echocardiography but without hemodynamic evidence of PH (n=12). Results In patients with PAH, TcPO2 and TcPCO2 were significantly associated with PaO2 (R= 0.44, p=0.03) and PaCO2 (R=0.77, p<0.001), respectively. TcPO2/FiO2 (mean difference: −65.0 [95% CI: −121.3–8.7]) and TcPCO2 (mean difference: −7.4 [95% CI: −11.6–3.1]) were significantly lower in patients with PAH than healthy controls. TcPCO2 was useful in discriminating PAH patients from other individuals (AUC: 0.74 (95% CI of 0.62–0.83)). TcPO2/FiO2 ratio was significantly associated with mean PAP, TPG, PVR, CI, SVI, DLCO, 6-min walk distance and components of the CAMPHOR questionnaire. Conclusions Transcutaneous pressure of CO2 was lower in patients with PAH. Transcutaneous pressure of O2 over inspired fraction of O2 ratio was inversely associated with severity of disease in patients with pulmonary arterial hypertension. PMID:25641509

  11. 2014 Guidelines of Taiwan Society of Cardiology (TSOC) for the Management of Pulmonary Arterial Hypertension

    PubMed Central

    Hsu, Chih-Hsin; Ho, Wan-Jing; Huang, Wei-Chun; Chiu, Yu-Wei; Hsu, Tsu-Shiu; Kuo, Ping-Hung; Hsu, Hsao-Hsun; Chang, Jia-Kan; Cheng, Chin-Chang; Lai, Chao-Lun; Liang, Kae-Woei; Lin, Shoa-Lin; Sung, Hsao-Hsun; Tsai, Wei-Chuan; Weng, Ken-Pen; Hsieh, Kai-Sheng; Yin, Wei-Hsian; Lin, Shing-Jong; Wang, Kuo-Yang

    2014-01-01

    Pulmonary hypertension (PH) is a hemodynamic and pathophysiologic condition, defined as a mean pulmonary arterial pressure exceeding 25 mmHg at rest. According to the recent classifications, it is grouped into pulmonary arterial hypertension (PAH), heart-related, lung-related, thromboembolic, and miscellaneous PH. In the past two decades, tremendous advances have occurred in the field of PH. These include (1) development of clinical diagnostic algorithm and a monitoring strategy dedicated to PAH, (2) defining strong rationales for screening at-risk populations, (3) advent of pulmonary specific drugs which makes PAH manageable, (4) recognition of needs of having proper strategy of combining existing pulmonary specific drugs, and/or potential novel drugs, (5) pursuit of clinical trials with optimal surrogate endpoints and study durations, (6) recognition of critical roles of PH/right ventricular function, as well as interdependence of ventricles in different conditions, especially those with various phenotypes of heart failure, and (7) for rare diseases, putting equal importance on carefully designed observation studies, various registries, etc., besides double blind randomized studies. In addition, ongoing basic and clinical research has led to further understanding of relevant physiology, pathophysiology, epidemiology and genetics of PH/PAH. This guidelines from the working group of Pulmonary Hypertension of the Taiwan Society of Cardiology is to provide updated guidelines based on the most recent international guidelines as well as Taiwan’s domestic research on PH. The guidelines are mainly for the management of PAH (Group 1) ; however the majority of content can be helpful for managing other types of PH. PMID:27122817

  12. Increased finger arterial blood pressure after exercise detraining in women with parental hypertension: autonomic tasks.

    PubMed

    Buckworth, J; Convertino, V A; Cureton, K J; Dishman, R K

    1997-05-01

    The effects of exercise detraining on resting finger arterial blood pressure (BP), the carotid-cardiac vagal baroreflex, and BP and heart rate (HR) responses to mental arithmetic and forehead cold exposure were studied in young (19 +/- 1.1 years) normotensive women with parental history of hypertension. Following 8 weeks of aerobic exercise for 25 min, 3 days week-1 at an intensity of 60% VO2peak, subjects ceased training for 6-8 weeks. After detraining, VO2peak (mL kg-1 min-1) was reduced by 11.5% (41.1 +/- 6.9 to 36.4 +/- 4.8) coincident with an approximately equal to 10% increase in submaximal exercise heart rate. Responses to the laboratory tasks were then compared. Detraining was accompanied by increases (P < 0.05) in resting systolic (SBP) (113.6 +/- 8.9 to 121.2 +/- 9.0), diastolic (DBP) (63.0 +/- 8.4 to 68.3 +/- 6.8), and mean arterial (MAP) (78.7 +/- 8.4 to 84.2 +/- 7.3) BP (mmHg). None of the above changes occurred in sedentary matched-control subjects. Systolic blood pressure was elevated during forehead cold exposure and MAP was elevated during mental arithmetic after detraining, but the rates of response and recovery for SBP, DBP and MAP were not altered by detraining. Despite higher submaximal exercise HR after detraining, HR responses to autonomic challenges, including the carotid-cardiac vagal baroreflex, were unchanged between training and detraining. Our results indicate that exercise detraining increases resting finger arterial BP in young normotensive women at risk for hypertension with no effects on the rate of response or recovery of heart rate and BP during autonomic tasks known to elicit sympathetic and carotid-cardiac vagal activities in this population. The use of auscultatory brachial artery pressures in a similar study of women diagnosed with hypertension will clarify the clinical meaning of our findings. PMID:9179308

  13. An inadequate pulmonary vascular capacity and susceptibility to pulmonary arterial hypertension in broilers.

    PubMed

    Wideman, R F; Chapman, M E; Hamal, K R; Bowen, O T; Lorenzoni, A G; Erf, G F; Anthony, N B

    2007-05-01

    Broilers are susceptible to pulmonary hypertension syndrome (PHS; ascites syndrome) when their pulmonary vascular capacity is anatomically or functionally inadequate to accommodate the requisite cardiac output without an excessive elevation in pulmonary arterial pressure. The consequences of an inadequate pulmonary vascular capacity have been demonstrated experimentally and include elevated pulmonary vascular resistance (PVR) attributable to noncompliant, fully engorged vascular channels; sustained pulmonary arterial hypertension (PAH); systemic hypoxemia and hypercapnia; specific right ventricular hypertrophy, and right atrioventricular valve failure (regurgitation), leading to central venous hypertension and hepatic cirrhosis. Pulmonary vascular capacity is broadly defined to encompass anatomical constraints related to the compliance and effective volume of blood vessels, as well as functional limitations related to the tone (degree of constriction) maintained by the primary resistance vessels (arterioles) within the lungs. Surgical occlusion of 1 pulmonary artery halves the anatomical pulmonary vascular capacity, doubles the PVR, triggers PAH, eliminates PHS-susceptible broilers, and reveals PHS-resistant survivors whose lungs are innately capable of handling sustained increases in pulmonary arterial pressure and cardiac output. We currently are using i.v. microparticle injections to increase the PVR and trigger PAH sufficient in magnitude to eliminate PHS-susceptible individuals while allowing PHS-resistant individuals to survive as progenitors of robust broiler lines. The microparticles obstruct pulmonary arterioles and cause local tissues and responding leukocytes to release vasoactive substances, including the vasodilator NO and the highly effective vasoconstrictors thromboxane A(2) and serotonin [5-hydroxytryptamine (5-HT)]. Nitric oxide is the principal vasodilator responsible for modulating (attenuating) the PAH response and ensuing mortality triggered by

  14. Similar Adiponectin Levels in Obese Normotensive and Obese Hypertensive Men and No Vasorelaxant Effect of Adiponectin on Human Arteries.

    PubMed

    Dreier, Rasmus; Asferg, Camilla; Berg, Jais O; Andersen, Ulrik B; Flyvbjerg, Allan; Frystyk, Jan; Linneberg, Allan; Jeppesen, Jørgen L; Edvinsson, Lars; Skovsted, Gry F

    2016-02-01

    Obesity is a strong risk factor for hypertension, but the mechanism linking obesity to hypertension is not fully elucidated. In obesity, circulating concentrations of adiponectin are decreased and hypoadiponectinaemia has in some but not all studies been associated with increased risk of hypertension. Due to this inconsistency, we decided to study adiponectin from two aspects in a cross-sectional in vivo study and in an experimental in vitro study. In the cross-sectional study, 103 men with body mass index (BMI) ≥ 30.0 kg/m(2) were studied; 63 had 24-hr ambulatory blood pressure (ABP) ≥ 130/80 mmHg (ObeseHT) and 40 had 24-hr ABP < 130/80 mmHg (ObeseNT). As controls, we studied 27 men with BMI between 20.0 and 24.9 kg/m(2) and 24-hr ABP < 130/80 mmHg (LeanNT). Serum concentrations of adiponectin and body composition using dual-energy X-ray absorptiometry scanning were determined. In vitro, the direct vasomotor response of adiponectin was tested on subcutaneous resistance arteries from human abdominal adipose tissue. The two obese groups had lower adiponectin concentrations compared with LeanNT (p < 0.01) [median (interquartile range)]: ObeseHT 6.5 (5.1-8.3) mg/L; ObeseNT 6.6 (5.2-7.8) mg/L; and LeanNT 9.4 (6.7-12.4) mg/L, with no significant difference in adiponectin concentrations (or body composition) between ObeseHT and ObeseNT (p = 0.67). In vitro, adiponectin did not have any direct vasodilatory effect and adiponectin did not affect angiotensin II-stimulated vasoconstriction. In conclusion, obese hypertensive men have similar serum concentrations of adiponectin as obese normotensive men. In combination with the in vitro data, these findings question a pathogenic role of adiponectin in human hypertension. PMID:26272341

  15. Niflumic Acid Attenuated Pulmonary Artery Tone and Vascular Structural Remodeling of Pulmonary Arterial Hypertension Induced by High Pulmonary Blood Flow In Vivo.

    PubMed

    Wang, Kai; Ma, Jianfa; Pang, Yusheng; Lao, Jinquan; Pan, Xuanren; Tang, Qiaoyun; Zhang, Feng; Su, Danyan; Qin, Suyuan; Shrestha, Arnav Prasad

    2015-10-01

    Calcium-activated chloride channels (CaCCs) play a vital role in regulating pulmonary artery tone during pulmonary arterial hypertension (PAH) induced by high blood flow. The role of CaCCs inhibitor niflumic acid (NFA) in vivo during this process requires further investigation. We established the PAH model by abdominal shunt surgery and treated with NFA in vivo. Fifty rats were randomly divided into normal, sham, shunt, NFA group 1 (0.2 mg/kg), and NFA group 2 (0.4 mg/kg). Pathological changes, right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter were analyzed. Then contraction reactions of pulmonary arteries were measured. Finally, the electrophysiological characteristics of pulmonary arterial smooth muscle cells were investigated using patch-clamp technology. After 11 weeks of shunting, PAH developed, accompanied with increased right ventricle hypertrophy index, arterial wall area/vessel area, and arterial wall thickness/vessel external diameter. In the NFA treatment groups, the pressure and pathological changes were alleviated. The pulmonary artery tone in the shunt group increased, whereas it decreased after NFA treatment. The current density of CaCC was higher in the shunt group, and it was decreased in the NFA treatment groups. In conclusion, NFA attenuated pulmonary artery tone and structural remodeling in PAH induced by high pulmonary blood flow in vivo. CaCCs were involved and the augmented current density was alleviated by NFA treatment. PMID:26132368

  16. The role of collagen in extralobar pulmonary artery stiffening in response to hypoxia-induced pulmonary hypertension.

    PubMed

    Ooi, Chen Yen; Wang, Zhijie; Tabima, Diana M; Eickhoff, Jens C; Chesler, Naomi C

    2010-12-01

    Hypoxic pulmonary hypertension (HPH) causes extralobar pulmonary artery (PA) stiffening, which potentially impairs right ventricular systolic function. Changes in the extracellular matrix proteins collagen and elastin have been suggested to contribute to this arterial stiffening. We hypothesized that vascular collagen accumulation is a major cause of extralobar PA stiffening in HPH and tested our hypothesis with transgenic mice that synthesize collagen type I resistant to collagenase degradation (Col1a1(R/R)). These mice and littermate controls that have normal collagen degradation (Col1a1(+/+)) were exposed to hypoxia for 10 days; some were allowed to recover for 32 days. In vivo PA pressure and isolated PA mechanical properties and collagen and elastin content were measured for all groups. Vasoactive studies were also performed with U-46619, Y-27632, or calcium- and magnesium-free medium. Pulmonary hypertension occurred in both mouse strains due to chronic hypoxia and resolved with recovery. HPH caused significant PA mechanical changes in both mouse strains: circumferential stretch decreased, and mid-to-high-strain circumferential elastic modulus increased (P < 0.05 for both). Impaired collagen type I degradation prevented a return to baseline mechanical properties with recovery and, in fact, led to an increase in the low and mid-to-high-strain moduli compared with hypoxia (P < 0.05 for both). Significant changes in collagen content were found, which tended to follow changes in mid-to-high-strain elastic modulus. No significant changes in elastin content or vasoactivity were observed. Our results demonstrate that collagen content is important to extralobar PA stiffening caused by chronic hypoxia. PMID:20852040

  17. Differential expression of vasoactive mediators in microparticle-challenged lungs of chickens that differ in susceptibility to pulmonary arterial hypertension.

    PubMed

    Hamal, Krishna R; Wideman, Robert F; Anthony, Nicholas B; Erf, Gisela F

    2010-01-01

    Pulmonary hypertension syndrome (PHS; ascites) in fast growing meat-type chickens (broilers) is characterized by the onset of idiopathic pulmonary arterial hypertension (IPAH) leading to right-sided congestive heart failure and terminal ascites. Intravenous microparticle (MP) injection is a tool used by poultry geneticists to screen for the broilers that are resistant (RES) or susceptible (SUS) to IPAH in a breeding population. MPs occlude pulmonary arterioles and initiate focal inflammation, causing local tissues and responding leukocytes to release vasoactive mediators such as serotonin (5-HT), endothelin-1 (ET-1), and nitric oxide (NO). RT-PCR was used to examine the differences between RES and SUS broilers in terms of gene expression of ET-1, ET receptor types A and B (ET(A) and ET(B)), the serotonin transporter (SERT), serotonin receptors (5-HT(1A), 5-HT(2A), 5-HT(1B), 5-HT(2B)), endothelial NO synthase (eNOS), and inducible NOS (iNOS) in the lungs of these broilers before (0 h) and after (2, 6, 12, 24, and 48 h) MP injection. In SUS broilers MP injection elicited higher (P < 0.05) pulmonary expression of 5-HT(1A), 5-HT(2B), and ET-1, which promote vasoconstriction and proliferation of pulmonary arterial smooth muscle cells (PASMC). In RES broilers the MP injection elicited higher expression of eNOS, iNOS, and ET(B), which promote vasodilation and inhibit PASMC proliferation. These observations support the hypothesis that the resistance of broiler chickens to IPAH may be due to the higher expression of vasoactive mediators that favor enhanced vasodilation and attenuated vasoconstriction during MP injection challenges to the pulmonary vasculature. PMID:19907003

  18. Limiting collagen turnover via collagenase-resistance attenuates right ventricular dysfunction and fibrosis in pulmonary arterial hypertension.

    PubMed

    Golob, Mark J; Wang, Zhijie; Prostrollo, Anthony J; Hacker, Timothy A; Chesler, Naomi C

    2016-06-01

    Pulmonary arterial hypertension (PAH) is a severe form of pulmonary hypertension in which right ventricular (RV) afterload is increased and death typically occurs due to decompensated RV hypertrophy and failure. Collagen accumulation has been implicated in pulmonary artery remodeling, but how it affects RV performance remains unclear. Here, we sought to identify the role of collagen turnover, defined as the balance between collagen synthesis and degradation, in RV structure and function in PAH To do so, we exposed mutant (Col1a1(R/R)) mice, in which collagen type I degradation is impaired such that collagen turnover is reduced, and wild-type (Col1a1(+/+)) littermates to 14 days of chronic hypoxia combined with SUGEN treatment (HySu) to recapitulate characteristics of clinical PAH RV structure and function were measured by echocardiography, RV catheterization, and histology. Despite comparable increases in RV systolic pressure (Col1a1(+/+): 46 ± 2 mmHg; Col1a1(R/R): 47 ± 3 mmHg), the impaired collagen degradation in Col1a1(R/R) mice resulted in no RV collagen accumulation, limited RV hypertrophy, and maintained right ventricular-pulmonary vascular coupling with HySu exposure. The preservation of cardiac function in the mutant mice indicates a beneficial role of limited collagen turnover via impaired degradation in RV remodeling in response to chronic pressure overload. Our results suggest novel treatments that reduce collagen turnover may offer a new therapeutic strategy for PAH patients. PMID:27252252

  19. Activation of Calpain-2 by Mediators in Pulmonary Vascular Remodeling of Pulmonary Arterial Hypertension.

    PubMed

    Kovacs, Laszlo; Han, Weihong; Rafikov, Ruslan; Bagi, Zsolt; Offermanns, Stefan; Saido, Takaomi C; Black, Stephen M; Su, Yunchao

    2016-03-01

    Calpain mediates collagen synthesis and cell proliferation and plays an important role in pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). In the present study, we investigated whether and how calpain is activated by PAH mediators in pulmonary artery smooth muscle cells (PASMCs). These data show that smooth muscle-specific knockout of calpain attenuated and knockout of calpastatin potentiated pulmonary vascular remodeling and pulmonary hypertension. Treatment of PASMCs with the PAH mediators platelet-derived growth factor (PDGF), serotonin, H2O2, endothelin-1, and IL-6 caused significant increases in calpain activity, cell proliferation, and collagen-I protein level without changes in protein levels of calpain-1 and -2. The calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA/AM) did not affect calpain activation, but the extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 and knocking down of calpain-2 prevented calpain activation in PAH mediator-treated PASMCs. Mass spectrometry data showed that the phosphorylation of calpain-2 at serine (Ser) 50 was increased and the phosphorylation of calpain-2 at Ser369 was decreased in PDGF-treated PASMCs. The PDGF-induced increase in Ser50 phosphorylation of calpain-2 was prevented by PD98059, whereas dephosphorylation of calpain-2 at Ser369 was blocked by the protein phosphatase 2A inhibitor fostriecin. Furthermore, smooth muscle of pulmonary arteries in PAH animal models and patients with PAH showed higher levels of phospho-Ser50-calpain-2 (P-Ser50) and lower levels of phospho-Ser369-calpain-2 (P-Ser369). These data support that calpain modulates pulmonary vascular remodeling in PAH. PAH mediator-induced activation of calpain is caused by ERK1/2-dependent phosphorylation of calpain-2 at Ser50 and protein phosphatase 2A-dependent dephosphorylation of calpain-2 at Ser369 in pulmonary vascular remodeling of PAH. PMID:26248159

  20. Idiopathic Pulmonary Arterial Hypertension: An Avian Model for Plexogenic Arteriopathy and Serotonergic Vasoconstriction

    PubMed Central

    Wideman, Robert F.; Hamal, Krishna R.

    2011-01-01

    Idiopathic pulmonary arterial hypertension (IPAH) is a disease of unknown cause that is characterized by elevated pulmonary arterial pressure and pulmonary vascular resistance attributable to vasoconstriction and vascular remodeling of small pulmonary arteries. Vascular remodeling includes hypertrophy and hyperplasia of smooth muscle (medial hypertrophy) accompanied in up to 80% of the cases by the formation of occlusive plexiform lesions (plexogenic arteriopathy). Patients tend to be unresponsive to vasodilator therapy and have a poor prognosis for survival when plexogenic arteriopathy progressively obstructs their pulmonary arteries. Research is needed to understand and treat plexogenic arteriopathy, but advances have been hindered by the absence of spontaneously developing lesions in existing laboratory animal models. Young domestic fowl bred for meat production (broiler chickens, broilers) spontaneously develop IPAH accompanied by semi-occlusive endothelial proliferation that progresses into fully developed plexiform lesions. Plexiform lesions develop in both females and male broilers, and lesion incidences (lung sections with lesions/lung sections examined) averaged approximately 40% in 8 to 52 week old birds. Plexiform lesions formed distal to branch points in muscular interparabronchial pulmonary arteries, and were associated with perivascular mononuclear cell infiltrates. Serotonin (5-hydroxytryptamine, 5-HT) is a potent vasoconstrictor and mitogen known to stimulate vascular endothelial and smooth muscle cell proliferation. Serotonin has been directly linked to the pathogenesis of IPAH in humans, including IPAH linked to serotonergic anorexigens that trigger the formation of plexiform lesions indistinguishable from those observed in primary IPAH triggered by other causes. Serotonin also plays a major role in the susceptibility of broilers to IPAH. This avian model of spontaneous IPAH constitutes a new animal model for biomedical research focused on the

  1. Impact of hypertension on the accuracy of exercise stress myocardial perfusion imaging for the diagnosis of coronary artery disease

    PubMed Central

    Elhendy, A; van Domburg, R T; Sozzi, F; Poldermans, D; Bax, J; Roelandt, J

    2001-01-01

    AIM—To compare the accuracy of exercise stress myocardial perfusion single photon emission computed tomography (SPECT) imaging for the diagnosis of coronary artery disease in patients with and without hypertension.
METHODS—A symptom limited bicycle exercise stress test in conjunction with 99m technetium sestamibi or tetrofosmin SPECT imaging was performed in 332 patients (mean (SD) age, 57 (10) years; 257 men, 75 women) without previous myocardial infarction who underwent coronary angiography. Of these, 137 (41%) had hypertension. Rest SPECT images were acquired 24 hours after the stress test. An abnormal scan was defined as one with reversible or fixed perfusion defects.
RESULTS—In hypertensive patients, myocardial perfusion abnormalities were detected in 79 of 102 patients with significant coronary artery disease and in nine of 35 patients without. In normotensive patients, myocardial perfusion abnormalities were detected in 104 of 138 patients with significant coronary artery disease and in 16 of 57 patients without. There were no differences between normotensive and hypertensive patients in sensitivity (77% (95% confidence interval (CI) 69% to 86%) v 75% (95% CI 68% to 83%)), specificity (74% (95% CI 60% to 89%) v 72% (95% CI 60% to 84%)), and accuracy (77% (95% CI 70% to 84%) v 74% (95% CI 68% to 80%)) of exercise SPECT for diagnosing coronary artery disease. The accuracy of SPECT was greater than electrocardiography, both in hypertensive patients (p = 0.005) and in normotensive patients (p = 0.0001). For the detection of coronary artery disease in individual vessels, sensitivity was 58% (95% CI 51% to 65%) v 57% (95% CI 51% to 64%), specificity was 86% (95% CI 82% to 90%) v 85% (95% CI 81% to 89%), and accuracy was 74% (95% CI 70% to 78%) v 74% (95% CI 70% to 78%) in patients with and without hypertension (NS).
CONCLUSIONS—In the usual clinical setting, the value of exercise myocardial perfusion scintigraphy for diagnosing

  2. [IDENTIFICATION OF OCCUPATIONAL RISK FOR ARTERIAL HYPERTENSION. REPORT II: ELIMINATION OF THE MODIFYNG INFLUENCE OF FACTORS OF CARDIOVASCULAR RISK].

    PubMed

    Maksimov, S A; Skripchenko, A E; Mikhailuts, A P; Artamonova, G V

    2016-01-01

    This study is a continuation of (Report I) identification of the occupational risk of arterial hypertension (AH) in 13 occupational groups (3842 workers, men). In previous work there was eliminated the influence of traditional factors of the cardiovascular risk, in this study there was implemented the identification of the components of a healthy worker effect (HWE) and the elimination of their influence on the occupational risks of hypertension. Identification and removal of components HWE--the effect of a healthy recruitment (EHR) and the effect of the healthy worker persisting to work (EHWPW--was carried out by the analytic rearranging of the standardized for age and obesity prevalence rate of arterial hypertension with the use of own methodological approaches. For the determination of the presence and severity of EHR there was performed an analysis of the initial prevalence rate of arterial hypertension in the youngest age groups (under 31 years). To overcome HER standardized for age and obesity indices of the arterial hypertension prevalence rate were adjusted by the ratio of the frequency of arterial hypertension in the most young occupational and reference comparable groups. Identification of HWPW was executed by comparing the frequency of AH among workers retiring within 3 years from the occupational groups when compared to the whole sample. Then on the additional risk value there was adjusted the overall prevalence rate of AH in the occupation profession to overcome EHWPW. As a result of the consistent correction and elimination of the influence of HWE components on the prevalence rate of AH, there were obtained risks values, primarily reflecting the impact of occupational factors which can be considered as true occupational risks. Factors of the cardiovascular risk and HWE significantly modified true occupational risks for AH in a number of occupational groups up to inversion. At the same time, the pronouncement of EHR has a paramount importance in the

  3. Interlobular arteries from two-kidney, one-clip Goldblatt hypertensive rats exhibit impaired vasodilator response to epoxyeicosatrienoic acids

    PubMed Central

    Sporková, Alexandra; Reddy, N. Rami; Falck, John R.; Imig, John D.; Kopkan, Libor; Sadowski, Janusz; Červenka, Luděk

    2016-01-01

    Background Small renal arteries have a significant role in regulation of renal hemodynamics and blood pressure (BP). To study potential changes in regulation of vascular function in hypertension, we examined renal vasodilatory responses of small arteries from nonclipped kidneys of the two-kidney, one-clip (2K1C) Goldblatt hypertensive rats to native epoxyeicosatrienoic acids (EETs) which are believed to be involved in regulation of renal vascular function and BP. Two newly synthesized EET analogs were also examined. Methods Renal interlobular arteries isolated from the nonclipped kidneys on day 28 after clipping were preconstricted with phenylephrine (PE), pressurized, and the effects of a 14,15-EET analog, native 14,15-EET, and 11,12-ether-EET-8ZE, an analog of 11,12-EET, on the vascular diameter were determined and compared to the responses of arteries from the kidneys of sham-operated rats. Results In the arteries from non-clipped kidneys isolated in the maintenance phase of Goldblatt hypertension the maximal vasodilatory response to 14,15-EET analog was 30.1 ± 2.8% versus 49.8 ± 7.2% in sham-operated rats; the respective values for 11,12-ther-EET-8ZE were 31.4± 6.4% versus 80.4±6%, and for native EETs they were 41.7 ± 6.6 % versus 62.8 ± 4.4 % (P ≤ 0.05 for each difference). Conclusions We propose that reduced vasodilatory action and decreased intrarenal bioavailability of EETs combined with intrarenal ANG II levels that are inappropriately high for hypertensive rats underlie functional derangements of the nonclipped kidneys of 2K1C Goldblatt hypertensive rats. These derangements could play an important role in pathophysiology of sustained BP elevation observed in this animal model of human renovascular hypertension. PMID:27140711

  4. A cohort evaluation on arterial stiffness and hypertensive disorders in pregnancy

    PubMed Central

    2012-01-01

    Background Hypertensive disorders in pregnancy are associated with systemic endothelial dysfunction leading to impaired physiological vasodilation. Recent evidence has shown central aortic pressures obtained through pulse wave analysis, at less than 14 weeks of gestation, to be predictive of pre-eclampsia. In light of this, we aimed to evaluate the role of central aortic stiffness in the prediction and discrimination of hypertensive disorders in pregnancy. Methods A cohort study of women with viable, singleton pregnancies at less than 14 weeks of amenorrhoea, and without multiple pregnancies, autoimmune or renal disease, diagnosed with aneuploidy or fetal anomaly will be recruited from a single maternity hospital and followed up till delivery and puerperium. A targeted sample size of 1000 eligible pregnant women will be enrolled into the study from antenatal clinics. Main exposure under study is central aortic pulse pressure using radial pulse wave recording, and the outcomes under follow-up are gestational hypertension and pre-eclampsia. Other measures include lifestyle factors such as smoking, physical exercise, psychometric evaluations, vasoactive factors, uterine artery pulsatility index, height and weight measurements. These measures will be repeated over 4 antenatal visits at 11-14, 18-22, 28-32 and above 34 weeks of gestation. Double data entry will be performed on Microsoft Access, and analysis of data will include the use of random effect models and receiver operating characteristic curves on Stata 11.2. Discussion The proposed study design will enable a longitudinal evaluation of the central aortic pressure changes as a marker for vascular compliance during pregnancy. As measures are repeated over time, the timing and severity of changes are detectable, and findings may yield important information on how aberrant vascular responses occur and its role in the early detection and prediction of hypertensive disorders. PMID:23268774

  5. Efficacy and safety of mineralocorticoid receptors in mild to moderate arterial hypertension.

    PubMed

    Pelliccia, Francesco; Rosano, Giuseppe; Patti, Giuseppe; Volterrani, Maurizio; Greco, Cesare; Gaudio, Carlo

    2015-12-01

    The mineralocorticoid receptor antagonists have been shown to have favourable safety and cost-effectiveness profiles across a broad range of clinical indications, including heart failure, primary aldosteronism and resistant hypertension. The clinical biology of the first aldosterone blocker, i.e. spironolactone, and its effects in several organ systems has been well elucidated from multiple studies. The range of adverse effects experienced with spironolactone has led to its modification and the consequent synthesis of eplerenone. Scientific evidence accumulated so far supports the role of eplerenone as first-choice drug in heart failure, with lower prevalence rates of sex-related adverse effects associated with eplerenone as compared to spironolactone. In Europe, eplerenone is currently marketed only in some countries and only with the indication of heart failure, whereas its clinical efficacy and safety in mild to moderate hypertension is said to be uncertain. A review of available scientific evidence, however, discloses that 11 randomized clinical trials assessing eplerenone in >3500 hypertensives have been reported so far. The results of these studies clearly show that eplerenone is an effective antihypertensive agent when used alone or in combination with other medications. In doses ranging from 25 to 100mg daily, eplerenone monotherapy results in a dose-dependent reduction in clinic blood pressure. As compared to placebo, eplerenone reduces significantly blood pressure from baseline. In general, 100mg daily eplerenone has a blood pressure lowering that is 50 to 75% that of spironolactone. Eplerenone results in a greater reduction in blood pressure as compared with losartan, and comparison between eplerenone and amlodipine shows that both treatments decrease systolic blood pressure to a similar extent but eplerenone is better tolerated. In conclusion, there is now evidence that eplerenone can play an important role in the treatment of mild to moderate arterial

  6. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension.

    PubMed

    Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi

    2016-01-01

    We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH. PMID:27419193

  7. Constitutively active form of natriuretic peptide receptor 2 ameliorates experimental pulmonary arterial hypertension

    PubMed Central

    Nawa, Nobutoshi; Ishida, Hidekazu; Katsuragi, Shinichi; Baden, Hiroki; Takahashi, Kunihiko; Higeno, Ryota; Torigoe, Fumiko; Mihara, Seiko; Narita, Jun; Miura, Kohji; Nakamura, Kazufumi; Kogaki, Shigetoyo; Ozono, Keiichi

    2016-01-01

    We recently found a constitutively active mutant of natriuretic peptide receptor 2 (caNPR2; V883M), which synthesizes larger amounts of cyclic guanosine monophosphate (cGMP) intracellularly without any ligand stimulation than existing drugs. The aim of this study was to investigate the therapeutic effects of gene transduction using caNPR2 for pulmonary arterial hypertension (PAH). In vitro gene transduction into human pulmonary arterial smooth muscle cells using Sendai virus (SeV) vectors carrying caNPR2 induced 10,000-fold increases in the synthesis of cGMP without ligand stimulation, and the proliferation of caNPR2-expressing cells was significantly attenuated. The PAH model rats generated by hypoxia and the administration of SU5416 were then treated with SeV vectors through a direct injection into the left pulmonary artery. Right ventricular systolic pressure was significantly decreased 2 weeks after the treatment, while systemic blood pressure remained unchanged. Histological analyses revealed that the medial wall thickness and occlusion rate of pulmonary arterioles were significantly improved in caNPR2-treated lungs. Neither the systemic integration of virus vectors nor side effects were observed. The massive stimulation of cGMP synthesis by gene therapy with caNPR2 was safe and effective in a PAH rat model and, thus, has potential as a novel therapy for patients with severe progressive PAH. PMID:27419193

  8. A Modified Verhoeff-Van Gieson Elastin Histochemical Stain to Enable Pulmonary Arterial Hypertension Model Characterization

    PubMed Central

    Percival, K.R.; Radi, Z.A.

    2016-01-01

    Optimal histochemical staining is critical to ensure excellent quality stained sections to enable light microscopic and histomorphometric image analysis. Verhoeff-van Gieson is the most widely used histochemical stain for the visualization of vascular elastic fibers. However, it is notoriously difficult to differentiate fine elastic fibers of small vasculature to enable histomorphometric image analysis, especially in organs such as the lung. A tissue fixation procedure of 10% neutral buffered formalin with subsequent fixation in 70% ethanol further compounds the problem of small vessel staining and identification. Therefore, a modified Verhoeff’s elastin stain was developed as a reliable method to optimally highlight the internal and external elastic laminae of small arteries (50-100 µm external diameter) and intra-acinar vessels (10-50 µm external diameter) in 3 µm thick lung tissue sections from models of pulmonary arterial hypertension. This modified Verhoeff’s elastin stain demonstrated well-defined staining of fine elastic fibers of pulmonary blood vessels enabling subsequent histomorphometric image analysis of vessel wall thickness in small arteries and intra-acinar vessels. In conclusion, modification of the standard Verhoeff-van Gieson histochemical stain is needed to visualize small caliber vessels’ elastic fibers especially in tissues fixed in 10% neutral buffered formalin followed by additional fixation in 70% ethanol. PMID:26972717

  9. Multimodality imaging in congenital heart disease-related pulmonary arterial hypertension.

    PubMed

    D'Alto, Michele; Dimopoulos, Konstantinos; Budts, Werner; Diller, Gerhard-Paul; Di Salvo, Giovanni; Dellegrottaglie, Santo; Festa, Pierluigi; Scognamiglio, Giancarlo; Rea, Gaetano; Ait Ali, Lamia; Li, Wei; Gatzoulis, Michael A

    2016-06-15

    Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. The present review aims to discuss the clinical applications of invasive and non-invasive diagnostic modalities and to describe the strengths and weaknesses of each technique. Chest radiograph is an inexpensive investigation providing information on pulmonary arterial and hilar dilatation, pruning of peripheral pulmonary arteries and cardiomegaly. Transthoracic two-dimensional and Doppler echocardiography is the most widely used imaging tool. It provides information on cardiac anatomy and an estimate of haemodynamics and biventricular remodelling and function. In addition, echocardiography is valuable in assessing prognosis and monitoring the efficacy of therapy. Structural and functional changes associated with CHD-PAH, mainly affecting the right ventricle and pulmonary circulation, may represent an ideal target for evaluation with cardiac magnetic resonance. This non-invasive imaging modality has a low biological impact. CT plays an important role for patients with limited echocardiographic windows and those who are unable to undergo MRI (claustrophobia, poor compliance, presence of a pacemaker/implantable cardioverter defibrillator). It is the modality of choice for detailed assessment of pulmonary vessel obstruction or thrombosis. Finally, heart catheterisation remains the gold standard for diagnosing and confirming PAH in patients with CHD and for shunt evaluation. The diagnostic assessment of CHD-PAH requires great expertise and a deep knowledge of both CHD and PAH pathophysiology and should take place in a tertiary centre, where multiple data can be appropriately integrated and applied clinically. PMID:27013702

  10. Acute ileofemoral artery thromboembolism due to left ventricle thrombi with spontaneous coronary artery dissection

    PubMed Central

    Jun, Heungman; Jung, Cheol-Woong

    2015-01-01

    Spontaneous coronary artery dissection (SCAD) is a very rare cause of peripheral artery thromboembolism. It is especially rare to show symptoms of acute limb ischemia without chest symptoms during a hospital visit. In this case, a rare case of SCAD led to left heart failure and caused left ventricle thrombi, which in turn caused peripheral thromboembolism. PMID:25553326

  11. Adverse Events in Connective Tissue Disease–Associated Pulmonary Arterial Hypertension

    PubMed Central

    Rhee, Rennie L.; Gabler, Nicole B.; Praestgaard, Amy; Merkel, Peter A.; Kawut, Steven M.

    2016-01-01

    Objective Patients with connective tissue disease (CTD)–associated pulmonary arterial hypertension (PAH) have a poorer prognosis compared to those with idiopathic PAH, but little is known about the differences in treatment-related adverse events (AEs) and serious adverse events (SAEs) between these groups. This study was undertaken to characterize these differences. Methods Individual patient-level data from 10 randomized controlled trials of therapies for PAH were obtained from the US Food and Drug Administration. Patients diagnosed as having either CTD-associated PAH or idiopathic PAH were included. A treatment-by-diagnosis interaction term was used to examine whether the effect of treatment on occurrence of AEs differed between patients with CTD-associated PAH and those with idiopathic PAH. Studies were pooled using fixed-effect models. Results The study sample included 2,370 participants: 716 with CTD-associated PAH and 1,654 with idiopathic PAH. In the active treatment group compared to the placebo group, the risk of AEs was higher among patients with CTD-associated PAH than among those with idiopathic PAH (odds ratio [OR] 1.57, 95% confidence interval [95% CI] 1.00–2.47 versus OR 0.94, 95% CI 0.69–1.26; P for interaction = 0.061), but there was no difference in the risk of SAEs in analyses adjusted for age, race, sex, hemodynamic findings, and laboratory values. Despite the higher occurrence of AEs in patients with CTD-associated PAH assigned to active therapy compared to those receiving placebo, the risk of drug discontinuation due to an AE was similar to that in patients with idiopathic PAH assigned to active therapy (P for interaction = 0.27). Conclusion Patients with CTD-associated PAH experienced more treatment-related AEs compared to those with idiopathic PAH in therapeutic clinical trials. These findings suggest that the overall benefit of advanced therapies for PAH may be attenuated by the greater frequency of AEs. PMID:26016953

  12. Short term effects of exercise training on exercise capacity and quality of life in patients with pulmonary arterial hypertension: protocol for a randomised controlled trial

    PubMed Central

    2011-01-01

    Background Advances in the understanding and management of pulmonary arterial hypertension have enabled earlier diagnosis and improved prognosis. However, despite best available therapy, symptoms of exertional dyspnoea and fatigue are commonly reported and result in a reduced capacity to perform daily activities and impaired quality of life. Exercise training has demonstrated efficacy in individuals with other respiratory and cardiovascular diseases. Historically, however, exercise training has not been utilised as a form of therapy in pulmonary arterial hypertension due to the perceived risk of sudden cardiac death and the theoretical possibility that exercise would lead to worsening pulmonary vascular haemodynamics and deterioration in right heart function. Now, with the advances in pharmaceutical management, determining the safety and benefits of exercise training in this population has become more relevant. Only three studies of supervised exercise training in pulmonary arterial hypertension have been published. These studies demonstrated improvements in exercise capacity and quality of life, in the absence of adverse events or clinical deterioration. However, these studies have not utilised an outpatient-based, whole body exercise training program, the most common format for exercise programs within Australia. It is uncertain whether this form of training is beneficial and capable of producing sustained benefits in exercise capacity and quality of life in this population. Design/Methods This randomised controlled trial will determine whether a 12 week, outpatient-based, supervised, whole body exercise training program, followed by a home-based exercise program, is safe and improves exercise capacity and quality of life in individuals with pulmonary arterial hypertension. This study aims to recruit 34 subjects who will be randomly allocated to the exercise group (supervised exercise training 3 times a week for 12 weeks, followed by 3 sessions per week of home

  13. Mild Renal Artery Stenosis Can Induce Renovascular Hypertension and is Associated with Elevated Renal Vein Renin Secretion.

    PubMed

    Balamuthusamy, Saravanan; Kannan, Arun; Thajudeen, Bijin; Ottley, Dean; Jalandhara, Nishant

    2015-01-01

    Renovascular hypertension is a syndrome which encompasses the physiological response of the kidney to changes in renal blood flow and renal perfusion pressure. Such physiological changes can occur with renal artery occlusion irrespective of the severity of the lesion. We have analyzed hypertensive patients with mild renal artery stenosis and compared them to patients with no stenosis. Renal vein renin sampling from catheterization of the renal vein was performed in all these patients. Patients with mild stenosis had higher renal vein renin ratio (3.01 ± 1.5) than the patients with no stenosis (1.10 ± 0.29; p = 0.002). Patients with mild stenosis were also found to have higher diastolic blood pressure and renal artery resistive indices when compared to patients with no stenosis. We therefore conclude that mild stenosis can precipitate renin-mediated hypertension in renovascular stenosis and also emphasis that parameters pertinent to renal physiology need to be evaluated before considering treatment options in patients with renal artery stenosis and medical management with RAAS blockade is the preferred modality of therapy for patients with renin-mediated hypertension. PMID:24943669

  14. Abnormal uterine artery remodelling in the stroke prone spontaneously hypertensive rat

    PubMed Central

    Small, Heather Y.; Morgan, Hannah; Beattie, Elisabeth; Griffin, Sinead; Indahl, Marie; Delles, Christian; Graham, Delyth

    2016-01-01

    Introduction The stroke prone spontaneously hypertensive rat (SHRSP) is an established model of human cardiovascular risk. We sought to characterise the uteroplacental vascular response to pregnancy in this model and determine whether this is affected by the pre-existing maternal hypertension. Methods Doppler ultrasound and myography were utilised to assess uterine artery functional and structural changes pre-pregnancy and at gestational day 18 in SHRSP (untreated and nifedipine treated) and in the normotensive Wistar-Kyoto (WKY) rat. Maternal adaptations to pregnancy were also assessed along with histology and expression of genes involved in oxidative stress in the placenta. Results SHRSP uterine arteries had a pulsatile blood flow and were significantly smaller (70906 ± 3903 μm2 vs. 95656 ± 8524 μm2 cross-sectional area; p < 0.01), had a significant increase in contractile response (57.3 ± 10.5 kPa vs 27.7 ± 1.9 kPa; p < 0.01) and exhibited impaired endothelium-dependent vasorelaxation (58.0 ± 5.9% vs 13.9 ± 4.6%; p < 0.01) compared to WKY. Despite significant blood pressure lowering, nifedipine did not improve uterine artery remodelling, function or blood flow in SHRSP. Maternal plasma sFLT-1/PlGF ratio (5.3 ± 0.3 vs 4.6 ± 0.1; p < 0.01) and the urinary albumin/creatinine ratio (1.9 ± 0.2 vs 0.6 ± 0.1; p < 0.01) was increased in SHRSP vs WKY. The SHRSP placenta had a significant reduction in glycogen cell content and an increase in Hif1α, Sod1 and Vegf. Discussion We conclude that the SHRSP exhibits a number of promising characteristics as a model of spontaneous deficient uteroplacental remodelling that adversely affect pregnancy outcome, independent of pre-existing hypertension. PMID:26612342

  15. From gene to protein—experimental and clinical studies of ACE2 in blood pressure control and arterial hypertension

    PubMed Central

    Patel, Sheila K.; Velkoska, Elena; Freeman, Melanie; Wai, Bryan; Lancefield, Terase F.; Burrell, Louise M.

    2014-01-01

    Hypertension is a major risk factor for stroke, coronary events, heart and renal failure, and the renin-angiotensin system (RAS) plays a major role in its pathogenesis. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II. An “alternate” arm of the RAS now exists in which ACE2 counterbalances the effects of the classic RAS through degradation of Ang II, and generation of the vasodilator Ang 1-7. ACE2 is highly expressed in the heart, blood vessels, and kidney. The catalytically active ectodomain of ACE2 undergoes shedding, resulting in ACE2 in the circulation. The ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats, suggesting that ACE2 may be a candidate gene for hypertension. It is hypothesized that disruption of tissue ACE/ACE2 balance results in changes in blood pressure, with increased ACE2 expression protecting against increased blood pressure, and ACE2 deficiency contributing to hypertension. Experimental hypertension studies have measured ACE2 in either the heart or kidney and/or plasma, and have reported that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, hence increasing ACE2 may be a therapeutic option for the management of high blood pressure in man. There have been relatively few studies of ACE2, either at the gene or the circulating level in patients with hypertension. Plasma ACE2 activity is low in healthy subjects, but elevated in patients with cardiovascular risk factors or cardiovascular disease. Genetic studies have investigated ACE2 gene polymorphisms with either hypertension or blood pressure, and have produced largely inconsistent findings. This review discusses the evidence regarding ACE2 in experimental hypertension models and the association between circulating ACE2 activity and ACE2 polymorphisms with blood pressure and arterial

  16. Types of Pulmonary Hypertension

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Pulmonary Hypertension The World Health Organization divides pulmonary hypertension (PH) ... are called pulmonary hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no ...

  17. Aliskiren – an alternative to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in the therapy of arterial hypertension

    PubMed Central

    Hoffmann, Karolina; Bryl, Wiesław; Minczykowski, Andrzej

    2013-01-01

    There has been enormous progress in antihypertensive therapy over the last few decades. However, the management of arterial hypertension is still insufficient and more efforts are needed to improve both non-pharmacological and pharmacological treatment of this widely prevalent disease. Renin-angiotensin-aldosterone system (RAAS) inhibition is crucial both for blood pressure (BP) control and for prevention of organ damage or its development in patients with hypertension. Angiotensin-converting enzyme inhibitors and/or sartans block RAAS incompletely. Aliskiren is one of the novel drugs that has been introduced to antihypertensive therapy recently. Up to now no trial has confirmed that aliskiren is efficacious in reducing cardiovascular events. Double RAAS blockade with aliskiren was not always safe. This review article presents the current view on the place of aliskiren in the therapy of arterial hypertension. PMID:25276171

  18. Aliskiren - an alternative to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in the therapy of arterial hypertension.

    PubMed

    Zaporowska-Stachowiak, Iwona; Hoffmann, Karolina; Bryl, Wiesław; Minczykowski, Andrzej

    2014-08-29

    There has been enormous progress in antihypertensive therapy over the last few decades. However, the management of arterial hypertension is still insufficient and more efforts are needed to improve both non-pharmacological and pharmacological treatment of this widely prevalent disease. Renin-angiotensin-aldosterone system (RAAS) inhibition is crucial both for blood pressure (BP) control and for prevention of organ damage or its development in patients with hypertension. Angiotensin-converting enzyme inhibitors and/or sartans block RAAS incompletely. Aliskiren is one of the novel drugs that has been introduced to antihypertensive therapy recently. Up to now no trial has confirmed that aliskiren is efficacious in reducing cardiovascular events. Double RAAS blockade with aliskiren was not always safe. This review article presents the current view on the place of aliskiren in the therapy of arterial hypertension. PMID:25276171

  19. mTORC2 coordinates pulmonary artery smooth muscle cell metabolism, proliferation and survival in pulmonary arterial hypertension

    PubMed Central

    Goncharov, Dmitry A.; Kudryashova, Tatiana V.; Ziai, Houman; Ihida-Stansbury, Kaori; DeLisser, Horace; Krymskaya, Vera P.; Tuder, Rubin M.; Kawut, Steven M.; Goncharova, Elena A.

    2014-01-01

    Background Enhanced proliferation, resistance to apoptosis and metabolic shift to glycolysis of pulmonary arterial vascular smooth muscle cells (PAVSMC) are key pathophysiological components of pulmonary vascular remodeling in idiopathic pulmonary arterial hypertension (IPAH). The role of distinct mTOR complexes mTORC1 (mTOR-raptor) and mTORC2 (mTOR-rictor) in PAVSMC proliferation and survival in PAH and their therapeutic relevance is unknown. Methods and Results Immunohistochemical and immunoblot analyses revealed that mTORC1 and mTORC2 pathways are markedly up-regulated in small remodeled PAs and isolated distal PAVSMC from IPAH subjects that have increased ATP levels, proliferation and survival that depend on glycolytic metabolism. siRNA- and pharmacological-based analysis showed that while both mTORC1 and mTORC2 contributing to proliferation, only mTORC2 is required for ATP generation and survival of IPAH PAVSMC. mTORC2 down-regulated energy sensor AMPK allowing activation of mTORC1-S6 and increased proliferation, and deficiency of pro-apoptotic protein Bim and IPAH PAVSMC survival. Nox4 protein levels were increased in IPAH PAVSMC that was necessary for mTORC2 activation, proliferation and survival. Nox4 levels and mTORC2 signaling were significantly up-regulated in small PAs from hypoxia-exposed rats at days 2-28 of hypoxia. Treatment with the mTOR kinase inhibitor PP242 at days 15-28 suppressed mTORC2, but not Nox4, induced SM-specific apoptosis in small PAs and reversed hypoxia-induced pulmonary vascular remodeling in rats. Conclusions These data provide a novel mechanistic link of Nox4-dependent activation of mTORC2 via energy sensor AMPK to increased proliferation and survival of PAVSMC in PAH suggesting a new potential pathway for the therapeutic interventions. PMID:24270265

  20. Salvianolic acid A attenuates vascular remodeling in a pulmonary arterial hypertension rat model

    PubMed Central

    Chen, Yu-cai; Yuan, Tian-yi; Zhang, Hui-fang; Wang, Dan-shu; Yan, Yu; Niu, Zi-ran; Lin, Yi-huang; Fang, Lian-hua; Du, Guan-hua

    2016-01-01

    Aim: The current therapeutic approaches have a limited effect on the dysregulated pulmonary vascular remodeling, which is characteristic of pulmonary arterial hypertension (PAH). In this study we examined whether salvianolic acid A (SAA) extracted from the traditional Chinese medicine 'Dan Shen' attenuated vascular remodeling in a PAH rat model, and elucidated the underlying mechanisms. Methods: PAH was induced in rats by injecting a single dose of monocrotaline (MCT 60 mg/kg, sc). The rats were orally treated with either SAA (0.3, 1, 3 mg·kg−1·d−1) or a positive control bosentan (30 mg·kg−1·d−1) for 4 weeks. Echocardiography and hemodynamic measurements were performed on d 28. Then the hearts and lungs were harvested, the organ indices and pulmonary artery wall thickness were calculated, and biochemical and histochemical analysis were conducted. The levels of apoptotic and signaling proteins in the lungs were measured using immunoblotting. Results: Treatment with SAA or bosentan effectively ameliorated MCT-induced pulmonary artery remodeling, pulmonary hemodynamic abnormalities and the subsequent increases of right ventricular systolic pressure (RVSP). Furthermore, the treatments significantly attenuated MCT-induced hypertrophic damage of myocardium, parenchymal injury and collagen deposition in the lungs. Moreover, the treatments attenuated MCT-induced apoptosis and fibrosis in the lungs. The treatments partially restored MCT-induced reductions of bone morphogenetic protein type II receptor (BMPRII) and phosphorylated Smad1/5 in the lungs. Conclusion: SAA ameliorates the pulmonary arterial remodeling in MCT-induced PAH rats most likely via activating the BMPRII-Smad pathway and inhibiting apoptosis. Thus, SAA may have therapeutic potential for the patients at high risk of PAH. PMID:27180980

  1. Hemoptysis due to a mycotic pulmonary artery aneurysm in an injecting drug user.

    PubMed

    Papaioannou, Vasilios; Mikroulis, Dimitrios; Chrysafis, Ioannis; Fotakis, Stelios; Pneumatikos, Ioannis

    2014-08-01

    Infected aneurysms of the pulmonary artery are a rare consequence of injected drug use. Hemoptysis of pulmonary arterial origin is also infrequent; however, the mortality is as high as 50%. We report here a case of hemoptysis in an intravenous drug user, caused by a pulmonary artery aneurysm due to septic microemboli, originating from a groin abscess. We highlight the importance of recognizing and treating thromboembolic complications associated with deep venous thrombosis in injecting drug users. PMID:23250844

  2. Pathological role of a constitutively active population of alpha(1D)-adrenoceptors in arteries of spontaneously hypertensive rats.

    PubMed

    Gisbert, Regina; Ziani, Khalid; Miquel, Raquel; Noguera, M Antonia; Ivorra, M Dolores; Anselmi, Elsa; D'Ocon, Pilar

    2002-01-01

    1. The role of a constitutively active population of alpha(1D)-adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg(-1) per day orally) in order to prevent the hypertensive state. 2. In adult SHR, a significant increase in BMY 7378 potency (not in prazosin potency) was observed in aorta, mesenteric artery, and the first and second branches of the small mesenteric arteries with respect to WKY rats. This difference was not observed in iliac and tail arteries, which suggests an increased functional role of alpha(1D)-adrenoceptors only in some vessels of SHR. 3. The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of alpha(1D)-adrenoceptors, was also significantly greater in aorta and mesenteric artery from adult SHR. 4. In young and captopril treated adult animals, no differences between strains with respect to BMY 7378 potency, or IRT were observed. 5. The increase in the functional role of alpha(1D)-adrenoceptors and their constitutive activity observed in hypertension is prevented by captopril treatment. The pathological consequence of this change is the slower rate of recovery of the basal tone after removal of an adrenergic stimulus, observed in vessels from hypertensive animals that had shown an increase in the functionality of constitutively active alpha(1D)-adrenoceptors. This change was not observed in prehypertensive or captopril treated animals. PMID:11786496

  3. Pathological role of a constitutively active population of α1D-adrenoceptors in arteries of spontaneously hypertensive rats

    PubMed Central

    Gisbert, Regina; Ziani, Khalid; Miquel, Raquel; Noguera, M Antonia; Ivorra, M Dolores; Anselmi, Elsa; D'Ocon, Pilar

    2002-01-01

    The role of a constitutively active population of α1D-adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg−1 per day orally) in order to prevent the hypertensive state.In adult SHR, a significant increase in BMY 7378 potency (not in prazosin potency) was observed in aorta, mesenteric artery, and the first and second branches of the small mesenteric arteries with respect to WKY rats. This difference was not observed in iliac and tail arteries, which suggests an increased functional role of α1D-adrenoceptors only in some vessels of SHR.The increase in the resting tone (IRT) observed in absence of agonist, inhibited by BMY 7378, that represents the constitutively active population of α1D-adrenoceptors, was also significantly greater in aorta and mesenteric artery from adult SHR.In young and captopril treated adult animals, no differences between strains with respect to BMY 7378 potency, or IRT were observed.The increase in the functional role of α1D-adrenoceptors and their constitutive activity observed in hypertension is prevented by captopril treatment. The pathological consequence of this change is the slower rate of recovery of the basal tone after removal of an adrenergic stimulus, observed in vessels from hypertensive animals that had shown an increase in the functionality of constitutively active α1D-adrenoceptors. This change was not observed in prehypertensive or captopril treated animals. PMID:11786496

  4. Drugs and toxins-associated pulmonary arterial hypertension: lessons learned and challenges ahead.

    PubMed

    de Jesus Perez, V; Kudelko, K; Snook, S; Zamanian, R T

    2011-01-01

    Since the identification of the link between pulmonary arterial hypertension (PAH) and exposure to certain drugs and toxins nearly fifty years ago, the expanding landscape of available pharmaceuticals and illicit drugs is further fueling this association. While some causative agents in drugs and toxins associated PAH (D&T-APAH) have been identified, little is known about the exact biology and clinical implications of the disease. In this review, we discuss the historical evidence that links PAH with exposure to anorexinogens, cocaine, and methamphetamines and concentrate on what is known about potential pathogenesis, clinical manifestations, and current management. We conclude that future research should focus on studies looking at clinical outcome and susceptibility factors. PMID:21176010

  5. Safety and tolerability considerations in the use of sildenafil for children with pulmonary arterial hypertension

    PubMed Central

    Dodgen, Andrew L; Hill, Kevin D

    2015-01-01

    Sildenafil is a phosphodiesterase type-5 inhibitor approved for treatment of pulmonary arterial hypertension (PAH) in adults. Data from pediatric trials demonstrate a similar acute safety profile to the adult population but have raised concerns regarding the safety of long-term use in children. Interpretation of these trials remains controversial with major regulatory agencies differing in their recommendations – the US Food and Drug Administration recommends against the use of sildenafil for treatment of PAH in children, while the European Medicines Agency supports its use at “low doses”. Here, we review the available pediatric data regarding dosing, acute, and long-term safety and efficacy of sildenafil for the treatment of PAH in children. PMID:26719728

  6. Intra-abdominal bleeding during treprostinil infusion in a patient with pulmonary arterial hypertension

    PubMed Central

    Mindus, Stephanie; Pawlowski, Jacek; Nisell, Magnus; Ferrara, Giovanni

    2013-01-01

    Medical treatment of pulmonary arterial hypertension (PAH) is increasingly common. Prostacyclins were introduced in the early 90s, and treprostinil is one of the most frequently used drugs of this class today, owing to its long half-life and to the possibility to administer the molecule through several routes. Treprostinil is considered a safe drug and is associated with a significant improvement of exercise capacity, especially in patients with idiopathic PAH (iPAH). Systemic sclerosis-associated PAH (sc-PAH) correlates to a worse prognosis compared with that of iPAH. Despite these considerations, safety data on treprostinil are still limited and mainly derived from randomised controlled trials and retrospective studies with relatively small and heterogeneous cohorts of patients with PAH. We report the occurrence of a severe intra-abdominal bleeding during treprostinil infusion in a patient with sc-PAH. PMID:23446048

  7. Electrical carotid sinus stimulation: chances and challenges in the management of treatment resistant arterial hypertension.

    PubMed

    Chobanyan-Jürgens, Kristine; Jordan, Jens

    2015-09-01

    Treatment resistant arterial hypertension is associated with excess cardiovascular morbidity and mortality. Electrical carotid sinus stimulators engaging baroreflex afferent activity have been developed for such patients. Indeed, baroreflex mechanisms contribute to long-term blood pressure control by governing efferent sympathetic and parasympathetic activity. The first-generation carotid sinus stimulator applying bilateral bipolar stimulation reduced blood pressure in a controlled clinical trial but nevertheless failed to meet the primary efficacy endpoint. The second-generation device utilizes smaller unilateral unipolar electrodes, thus decreasing invasiveness of the implantation while saving battery. An uncontrolled clinical study suggested improvement in blood pressure with the second-generation device. We hope that these findings as well as preliminary observations suggesting cardiovascular and renal organ protection with electrical carotid sinus stimulation will be confirmed in properly controlled clinical trials. Meanwhile, we should find ways to better identify patients who are most likely to benefit from electrical carotid sinus stimulation. PMID:26208917

  8. The striated muscles in pulmonary arterial hypertension: adaptations beyond the right ventricle.

    PubMed

    Manders, Emmy; Rain, Silvia; Bogaard, Harm-Jan; Handoko, M Louis; Stienen, Ger J M; Vonk-Noordegraaf, Anton; Ottenheijm, Coen A C; de Man, Frances S

    2015-09-01

    Pulmonary arterial hypertension (PAH) is a fatal lung disease characterised by progressive remodelling of the small pulmonary vessels. The daily-life activities of patients with PAH are severely limited by exertional fatigue and dyspnoea. Typically, these symptoms have been explained by right heart failure. However, an increasing number of studies reveal that the impact of the PAH reaches further than the pulmonary circulation. Striated muscles other than the right ventricle are affected in PAH, such as the left ventricle, the diaphragm and peripheral skeletal muscles. Alterations in these striated muscles are associated with exercise intolerance and reduced quality of life. In this Back to Basics article on striated muscle function in PAH, we provide insight into the pathophysiological mechanisms causing muscle dysfunction in PAH and discuss potential new therapeutic strategies to restore muscle dysfunction. PMID:26113677

  9. Selexipag: An Oral and Selective IP Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.

    PubMed

    Asaki, Tetsuo; Kuwano, Keiichi; Morrison, Keith; Gatfield, John; Hamamoto, Taisuke; Clozel, Martine

    2015-09-24

    Prostacyclin controls cardiovascular function via activation of the prostacyclin receptor. Decreased prostacyclin production occurs in several cardiovascular diseases. However, the clinical use of prostacyclin and its analogues is complicated by their chemical and metabolic instability. A medicinal chemistry program searched for novel nonprostanoid prostacyclin receptor agonists not subject to these limitations. A compound with a diphenylpyrazine structural core was synthesized. Metabolic stability and agonist potency were optimized through modification of the linear side chain. Compound 12b (MRE-269, ACT-333679) was identified as a potent and highly selective prostacyclin receptor agonist. Replacement of the terminal carboxyl group with an N-acylsulfonamide group yielded parent compound 26a (selexipag, NS-304, ACT-293987), which is orally active and provides sustained plasma exposure of 12b. Compound 26a was developed for the treatment of pulmonary arterial hypertension and shown to reduce the risk of the composite morbidity/mortality end point in a phase 3 event-driven clinical trial. PMID:26291199

  10. Recent advances and future perspectives in therapeutic strategies for pulmonary arterial hypertension.

    PubMed

    Yao, Atsushi

    2012-11-01

    Since the innovation of epoprostenol, a prostacyclin analog, providing treatment for pulmonary arterial hypertension (PAH) in the 1990s, two types of oral drugs, endothelin receptor antagonists (ERAs) and phosphodiesterase V inhibitors, have further improved therapy for PAH. In contrast, it has become clear that the efficacy of monotherapy with these drugs is limited, and the establishment of combination therapies should be considered for PAH. Given that the newest PAH drugs include a receptor tyrosine kinase antagonist (imatinib), a soluble guanylate cyclase stimulator (riociguat), an oral analog of prostacyclin (selexipag), and a tissue targeting ERA (macitentan) determination of appropriate combinations for various etiologies and clinical stages is urgently required. In the next decade, it can be expected that the discovery of efficacious combination therapies, involving old and new drugs, will lead to significant advances in the treatment of PAH. PMID:23068290

  11. [Peculiarities of cardiac contractile function in patients with arterial hypertension depending on temperament and anxiety state].

    PubMed

    2011-01-01

    The aim of the work was to elucidate the relationship between temperament and personal anxiety and between left ventricular myocardium hypertrophy, contractility and diastolic function in 671 men (mean age 54 +/- 1.8 yr) with newly diagnosed grade II arterial hypertension who took no antihypertensive drugs before the study. The tone of vegetative nervous system, serum levels of cortisol, aldosterone, thyroxin, and insulin were measured. EchoCG was used to determine left ventricular myocardium mass (LVMM), LVMM index, the ratio of transmitral blood flow at the beginning and end of diastole, left ventricular ejection and shortening fractions, end-systolic and diastolic size and volume. Phlegmatic and melancholic patients differed from cholerics and sanguinics in the predominance of parasympathetic influences, elevated blood aldosterone and insulin levels in combination with higher LVMM and LVMM index but lower left ventricular systolic and diastolic function. These characteristics were especially well apparent in anxious subjects comprising a risk group for cardiac insufficiency. PMID:22420192

  12. Macitentan: An important addition to the treatment of pulmonary arterial hypertension

    PubMed Central

    Khadka, Anjan; Singh Brashier, Dick B; Tejus, Anantharamu; Sharma, Ashok Kumar

    2015-01-01

    Macitentan is an orphan drug for the treatment of pulmonary arterial hypertension (PAH). Endothelin-1 (ET-1) plays a critical role of pathophysiology of PAH. Macitentan, a new dual endothelin receptor antagonist, has reportedly improved prognosis of PAH patients by delaying the progression of disease. It prevents the binding of ET-1 to both endothelin A (ETA) and endothelin B (ETB) receptors. Macitentan displays higher efficacy, lesser adverse effects and drug interactions. It has completed phase III trials in 2012 for treatment of PAH and has been tried for ischemic digital ulcers in systemic sclerosis, recurrent glioblastoma and combination with chemotherapeutic agents against various cancers. Safety data for macitentan were obtained primarily from a placebo-controlled clinical study in 742 patients with PAH. The Food and Drug Administration (FDA) approved the drug on 13 October 2013. It is an important addition to long-term treatment of PAH. PMID:25709357

  13. Endothelin-1 receptor antagonists in fetal development and pulmonary arterial hypertension.

    PubMed

    de Raaf, Michiel Alexander; Beekhuijzen, Manon; Guignabert, Christophe; Vonk Noordegraaf, Anton; Bogaard, Harm Jan

    2015-08-15

    The Pregnancy Prevention Program (PPP) is in place to prevent drug-induced developmental malformations. Remarkably, among the ten PPP-enlisted drugs are three endothelin-1 (ET-1) receptor antagonists (ERA's: ambrisentan, bosentan and macitentan), which are approved for the treatment of Pulmonary Arterial Hypertension (PAH). This review describes the effects of ERA's in PAH pathobiology and cardiopulmonary fetal development. While ERA's hamper pathological remodeling of the pulmonary vasculature and as such exert beneficial effects in PAH, they disturb fetal development of cardiopulmonary tissues. By blocking ET-1-mediated positive inotropic effects and myocardial fetal gene induction, ERA's may affect right ventricular adaptation to the increased pulmonary vascular resistance in both the fetus and the adult PAH patient. PMID:26111581

  14. Drug Insight: endothelin-receptor antagonists for pulmonary arterial hypertension in systemic rheumatic diseases.

    PubMed

    Humbert, Marc; Simonneau, Gérald

    2005-12-01

    Rapid advances in the understanding of endothelin as a naturally occurring peptide with developmental and regulatory roles in normal physiology, along with a number of deleterious effects under pathologic conditions (including vasoconstriction, fibrosis, vascular hypertrophy, and inflammation) have led to the development of endothelin-receptor antagonists (ERAs). Bosentan, an antagonist with dual specificity for the endothelin-receptor subtypes A and B, has been shown to be efficacious and well tolerated in placebo-controlled clinical trials and is now approved in many countries, including the US, Canada, and Europe, for treatment of pulmonary arterial hypertension (PAH), including PAH associated with rheumatic diseases. ERAs with specificity for the endothelin-receptor subtype A, including sitaxsentan and ambrisentan, are currently undergoing investigation. This article reviews PAH associated with systemic rheumatic diseases and describes the role of ERAs in this setting. PMID:16932638

  15. Autoimmune hepatitis in a patient with pulmonary arterial hypertension treated with endothelin receptor antagonists.

    PubMed

    Naito, Akira; Terada, Jiro; Tanabe, Nobuhiro; Sugiura, Toshihiko; Sakao, Seiichiro; Kanda, Tatsuo; Yokosuka, Osamu; Tatsumi, Koichiro

    2014-01-01

    A 48-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension (PAH) and administered PAH-specific therapies, including bosentan. Four years after the initiation of treatment with bosentan, liver dysfunction appeared, and ambrisentan was substituted for bosentan. One-and-a half years later, a second episode of liver dysfunction occurred. The pathological findings of a liver biopsy specimen were not definitive, although drug-induced hepatotoxicity caused by ambrisentan was considered. However, the patient's liver dysfunction did not improve even after the discontinuation of ambrisentan. Finally, we diagnosed her with autoimmune hepatitis (AIH). Providing careful observation with a suspicion of AIH is important when treating PAH patients with autoantibodies. PMID:24694495

  16. Exercise testing and training in chronic lung disease and pulmonary arterial hypertension.

    PubMed

    Arena, Ross

    2011-01-01

    Research examining the clinical value of exercise testing and training in patients with chronic lung disease and pulmonary arterial hypertension (PAH) is less robust compared with cardiac populations but nevertheless highly supportive. Functional limitations are common in these patients, and exercise testing provides important information pertaining to the degree of this limitation, disease severity, and prognosis. Moreover, exercise testing, particularly in conjunction with ventilatory expired gas analysis, serves as a valuable diagnostic tool when the mechanism of the functional limitation and abnormal exertional symptoms is uncertain. Most work with respect to the benefits of exercise training has been performed in chronic obstructive lung disease cohorts and is used to support pulmonary rehabilitation. Emerging data indicate that exercise training is likewise beneficial in patients with interstitial lung disease and PAH. This review summarizes the evidence supporting the value of exercise testing and training and provides recommendations for clinical practice. PMID:21545932

  17. [Losartan for the correction of thrombocyte activity in patients suffering from arterial hypertension with metabolic syndrome].

    PubMed

    Simonenko, V B; medvedev, i N; Kumova, T A

    2008-01-01

    The aim of the study was to evaluate therapeutic effects of losartan on intravascular thrombocyte activity (ITA) in patients suffering from arterial hypertension with metabolic syndrome (MS). The subjects of the study were 35 patients administered losartan 50 mg a day for 4 months. The dynamics of the following parameters were evaluated: anthropometric parameters, blood lipids, lipid peroxidation in blood plasma and thrombocytes, the anti-oxidative protection of the liquid part of blood and platelets, and ITA. Student criterion was used for statistical analysis. In patients with AH and MS losartan had a positive effect on peroxidation syndrome and optimized ITA. To maintain the positive effects, prolonged administration of losartan is needed. In order to lower body mass in AH patients with MS losartan should be used in combination with non-drug means. PMID:18326282

  18. [Evaluation of the dose-effect relationship of perindopril in the treatment of arterial hypertension].

    PubMed

    Luccioni, R; Frances, Y; Gass, R; Gilgenkrantz, J M

    1989-05-01

    To evaluate the dose-effect relationship of antihypertensive drugs is essential to a rational determination of their effective dosage. Two double-blind and strictly controlled trials have demonstrated the effectiveness of perindopril 4 mg orally in the treatment of mild to moderate arterial hypertension (100 less than DAP less than 120 mmHg). The drug remained effective 24 hours after the last dose. The 2 mg dose proved insufficient to obtain a significant reduction of blood pressure. In case where the 4 mg dose was not sufficiently active, a better antihypertensive effect could be achieved with an 8 mg dose without major untoward reactions. The antihypertensive activity of perindopril was parallel to the percentage of angiotensin-converting enzyme inhibition induced by the compound. This study also illustrates clearly the value of semi-automatic blood pressure recording with the Dinamap system in the determination of dose-effect relationship, compared with the conventional sphygmomanometric method. PMID:2505712

  19. Upper-body extracorporeal membrane oxygenation as a strategy in decompensated pulmonary arterial hypertension

    PubMed Central

    Abrams, Darryl C.; Brodie, Daniel; Rosenzweig, Erika B.; Burkart, Kristin M.; Agerstrand, Cara L.; Bacchetta, Matthew D.

    2013-01-01

    Pulmonary arterial hypertension (PAH) is a disease with significant morbidity and mortality, particularly during an acute decompensation. We describe a single-center experience of three patients with severe Group 1 PAH, refractory to targeted medical therapy, in which an extubated, nonsedated, extracorporeal membrane oxygenation (ECMO) strategy with an upper-body configuration was used as a bridge to recovery or lung transplantation. All three patients were extubated within 24 hours of ECMO initiation. Two patients were successfully bridged to lung transplantation, and the other patient was optimized on targeted PAH therapy with subsequent recovery from an acute decompensation. The upper-body ECMO configuration allowed for daily physical therapy, including one patient, who would otherwise have been unsuitable for transplantation, ambulating over 850 meters daily. This series demonstrates the feasibility of using ECMO to bridge PAH patients to recovery or transplantation while avoiding the complications of immobility and invasive mechanical ventilation. PMID:24015346

  20. [Structural, developmental and functional evaluation of the family of individuals with arterial hypertension].

    PubMed

    Radovanovic, Cremilde Aparecida Trindade; Cecilio, Hellen Pollyanna Mantelo; Marcon, Sonia Silva

    2013-03-01

    The objective of the study was to evaluate the structure, development and functionality of the family that suffers from arterial hypertension. This is a qualitative study, developed with two families using the Calgary Model of Family Evaluation. It proposes the use of three categories of analysis: structural developmental and functional, and the use of a genogram and an ecomap. The two families are nuclear, however one is formed by the couple and their three sons who are married and reside in different homes. The other is a single-parent family established by the mother and children. The married son resides at another house in the same backyard with wife and daughter The application of the model of family evaluation allowed knowing the aspects related to the structure, operation and development of the two families that interfere impair or favor the development of the care in their quotidian. PMID:23781723

  1. Should patients with systemic sclerosis-related pulmonary arterial hypertension be anticoagulated?

    PubMed

    Nikpour, M; Stevens, W; Proudman, S M; Buchbinder, R; Prior, D; Zochling, J; Williams, T; Gabbay, E; Nandurkar, H

    2013-05-01

    Pulmonary arterial hypertension (PAH) is a major cause of mortality in scleroderma and despite 'advanced' therapies confers a median survival of less than 5 years. Anticoagulation in systemic sclerosis-related PAH (SSc-PAH) is currently one of the most contentious issues in the management of patients with connective tissue disease. While some studies have shown a survival benefit with warfarin therapy in this disease, others have not. Accordingly, a state of clinical equipoise exists in relation to anticoagulation in SSc-PAH. With an over fivefold reduction in mortality demonstrated in some observational studies, the issue of anticoagulation in SSc-PAH demands resolution through a well-designed randomised controlled trial. PMID:23668273

  2. Assessment of operability of patients with pulmonary arterial hypertension associated with congenital heart disease.

    PubMed

    Myers, Patrick O; Tissot, Cécile; Beghetti, Maurice

    2014-01-01

    Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease, and is now predominantly among patients with uncorrected left-to-right shunts. A growing population is characterized by persistent or recurrent PAH after surgical or interventional correction of left-to-right shunts; the latter having a worse prognosis than other forms of PAH associated with congenital heart disease. New treatments for PAH have been shown to be effective in improving PAH exercise capacity and hemodynamics, raising the hope for making previously inoperable congenital heart defects operable and shifting the framework for the assessment of operability. This review focuses on current methods for assessing operability in PAH associated with congenital heart disease, and the possibility of "treat-and-repair" vs. "repair-and-treat" strategies for patients with inoperable or borderline PAH. PMID:24225339

  3. Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary hypertension due to lung diseases and/or hypoxia

    PubMed Central

    Sakkijha, Husam; Idrees, Majdy M.

    2014-01-01

    Chronic lung diseases are common causes of pulmonary hypertension. It ranks second after the left heart disease. Both obstructive and restrictive lung diseases are know to cause pulmonary hypertension. The pathophysiology of the disease is complex, and includes factors affecting the blood vessels, airways, and lung parenchyma. Hypoxia and the inhalation of toxic materials are another contributing factors. Recent guidelines have further clarified the association between pulmonary hypertension and chronic lung disease and made general guidelines concerning the diagnosis and management. In this article, we will provide a detailed revision about the new classification and give general recommendations about the management of pulmonary hypertension in chronic lung diseases. PMID:25076998

  4. Identification of Candidate Genes in Scleroderma-Related Pulmonary Arterial Hypertension

    PubMed Central

    Grigoryev, DN; Mathai, SC; Fisher, MR; Girgis, RE; Zaiman, AL; Housten-Harris, T; Cheadle, C; Gao, L; Hummers, LK; Champion, HC; Garcia, JGN; Wigley, FM; Tuder, RM; Barnes, KC; Hassoun, PM

    2008-01-01

    We hypothesize that pulmonary arterial hypertension (PAH)-associated genes identified by expression profiling of peripheral blood mononuclear cells (PBMCs) from patients with idiopathic pulmonary arterial hypertension (IPAH) can also be identified in PBMCs from scleroderma patients with PAH (PAH-SSc). Gene expression profiles of PBMCs collected from IPAH (n=9), PAH-SSc (n=10) patients and healthy controls (n=5) were generated using HG_U133A_2.0 GeneChips and processed by RMA/GCOS_1.4/SAM_1.21 data analysis pipeline. Disease severity in consecutive patients was assessed by functional status and hemodynamic measurements. The expression profiles were analyzed using PAH severity-stratification, and identified candidate genes were validated with real time PCR (rtPCR). Transcriptomics of PBMCs from IPAH patients was highly comparable with that of PMBCs from PAH-SSc patients. The PBMC gene expression patterns significantly correlate with right atrium pressure (RA) and cardiac index (CI), known predictors of survival in PAH. Array stratification by RA and CI identified 364 PAH-associated candidate genes. Gene ontology analysis revealed significant (Zscore > 1.96) alterations in angiogenesis genes according to PAH severity: MMP9 and VEGF were significantly upregulated in mild as compared to severe PAH and healthy controls, as confirmed by rtPCR. These data demonstrate that PBMCs from patients with PAH-SSc carry distinct transcriptional expression. Furthermore, our findings suggest an association between angiogenesis-related gene expression and severity of PAH in PAH-SSc patients. Deciphering the role of genes involved in vascular remodeling and PAH development may reveal new treatment targets for this devastating disorder. PMID:18355767

  5. Survival benefits of warfarin in Korean patients with idiopathic pulmonary arterial hypertension

    PubMed Central

    Kang, Byung Ju; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Jae Seung

    2015-01-01

    Background/Aims: Idiopathic pulmonary arterial hypertension (IPAH) is an incurable disease with high mortality. Although most studies recommend anticoagulation treatment for IPAH, the benefits are uncertain, particularly in Korea, where it has not been studied. The purpose of this study was to evaluate survival outcomes of Korean patients with IPAH treated with warfarin. Methods: We performed a retrospective cohort study of patients diagnosed previously with pulmonary arterial hypertension (PAH) at the Asan Medical Center in Korea, between January 1994 and February 2013. We excluded patients with associated PAH, patients who did not undergo right heart catheterization (RHC), and patients with a positive vasoreactivity test. Patients in the study cohort were classified into a “warfarin group” and a “non-warfarin group,” according to the treatment they received during the first year after diagnosis. Results: We identified 31 patients with IPAH and a negative vasoreactivity test on RHC. Median patient age was 36.0 years, and 23 patients (74.2%) were female. The median time from the onset of symptoms to diagnosis was 19.0 months, and the most common presenting symptom was dyspnea. Survival rates of the patients at 1, 3, 5, and 10 years were 90.2%, 79.5%, 62.7%, and 34.8%, respectively. The mean survival period was 12.0 years in the warfarin group and 6.1 years in the non-warfarin group. Warfarin treatment had significant survival benefits in patients with IPAH (p = 0.023). Conclusions: Warfarin treatment substantially improved survival outcomes in Korean cases of IPAH. PMID:26552459

  6. Pulmonary haemorrhage due to an aortopulmonary collateral artery after arterial switch.

    PubMed

    Sugimoto, Ai; Ota, Noritaka; Sakamoto, Kisaburo

    2016-03-01

    A neonate with transposition of the great arteries and intact ventricular septum presented without pulmonary over-circulation, and subsequently developed pulmonary haemorrhage after corrective surgery. Postoperative CT revealed an aortopulmonary collateral artery arising from the descending aorta, and we performed successful embolisation on postoperative day 9. Aggressive imaging modalities such as angiography and/or CT imaging with contrast can detect unexpected extra-pulmonary blood supply and guide further management. PMID:26144860

  7. Reversible pulmonary arterial hypertension associated with interferon-beta treatment for multiple sclerosis

    PubMed Central

    Gibbons, E; Promislow, S; Davies, RA; Chandy, G; Stewart, DJ; Contreras-Dominguez, V; Pugliese, C; Dunne, R; Mielniczuk, LM

    2015-01-01

    Interferon (IFN) therapy has an important role in the treatment of multiple sclerosis and chronic hepatitis C infection. A few case reports have described an association between IFN therapy and the development of irreversible pulmonary arterial hypertension (PAH), and it is currently listed as a possible drug-induced cause of PAH in the most recent classification of pulmonary hypertension. A causal link between IFN use and PAH remains to be elucidated; many reports of PAH resulting from IFN occur in individuals with some other risk factor for PAH. The authors present a case involving a patient with multiple sclerosis with no known risk factors for PAH, who developed severe PAH after exposure to IFN therapy. The patient experienced significant clinical and hemodynamic improvement, with normalization of her pulmonary pressures after the initiation of combination therapy for PAH. At 28 months after diagnosis, she remains asymptomatic with no hemodynamic evidence of PAH and has been off all PAH therapy for 10 months. PMID:26083539

  8. Usefulness of High-Density Lipoprotein Cholesterol to Predict Survival in Pulmonary Arterial Hypertension.

    PubMed

    Larsen, Carolyn M; McCully, Robert B; Murphy, Joseph G; Kushwaha, Sudhir S; Frantz, Robert P; Kane, Garvan C

    2016-07-15

    It has been suggested that lipoprotein abnormalities may contribute to the pulmonary arteriolar dysfunction observed in pulmonary arterial hypertension (PAH). High-density lipoprotein cholesterol (HDL) has vasodilatory, anti-inflammatory, and endothelial protective properties. We hypothesized that a higher serum HDL level may be advantageous for survival in PAH and that the serum HDL level at diagnosis would be an independent predictor of survival in PAH and be additive to previously validated predictors of survival. This study included all patients with PAH seen at the Mayo Clinic Pulmonary Hypertension Clinic from January 1, 1995, to December 31, 2009, who had a baseline HDL measurement. Mortality was analyzed over 5 years using the Kaplan-Meier method. Univariate and multivariable Cox proportional hazards ratios were calculated to evaluate the relation between baseline HDL level and survival. HDL levels were available for 227 patients. Higher HDL levels were associated with significantly lower mortality. Patients with an HDL >54 mg/dl at diagnosis had a 5-year survival of 59%. By comparison those with an HDL <34 mg/dl had a 5-year survival of 30%. On multivariate analysis, higher HDL was associated with an age-adjusted risk ratio for death of 0.78 (CI 0.67 to 0.91; p <0.01) per 10 mg/dl increase. In conclusion, HDL was an independent predictor of survival in PAH. PMID:27291969

  9. Quality of Life on Arterial Hypertension: Validity of Known Groups of MINICHAL

    PubMed Central

    Soutello, Ana Lúcia Soares; Rodrigues, Roberta Cunha Matheus; Jannuzzi, Fernanda Freire; São-João, Thaís Moreira; Martini, Gabriela Giordano; Nadruz Jr., Wilson; Gallani, Maria-Cecília Bueno Jayme

    2015-01-01

    Introductions In the care of hypertension, it is important that health professionals possess available tools that allow evaluating the impairment of the health-related quality of life, according to the severity of hypertension and the risk for cardiovascular events. Among the instruments developed for the assessment of health-related quality of life, there is the Mini-Cuestionario of Calidad de Vida en la Hipertensión Arterial (MINICHAL) recently adapted to the Brazilian culture. Objective To estimate the validity of known groups of the Brazilian version of the MINICHAL regarding the classification of risk for cardiovascular events, symptoms, severity of dyspnea and target-organ damage. Methods Data of 200 hypertensive outpatients concerning sociodemographic and clinical information and health-related quality of life were gathered by consulting the medical charts and the application of the Brazilian version of MINICHAL. The Mann-Whitney test was used to compare health-related quality of life in relation to symptoms and target-organ damage. The Kruskal-Wallis test and ANOVA with ranks transformation were used to compare health-related quality of life in relation to the classification of risk for cardiovascular events and intensity of dyspnea, respectively. Results The MINICHAL was able to discriminate health-related quality of life in relation to symptoms and kidney damage, but did not discriminate health-related quality of life in relation to the classification of risk for cardiovascular events. Conclusion The Brazilian version of the MINICHAL is a questionnaire capable of discriminating differences on the health‑related quality of life regarding dyspnea, chest pain, palpitation, lipothymy, cephalea and renal damage. PMID:25993593

  10. Acute Response to Unilateral Unipolar Electrical Carotid Sinus Stimulation in Patients With Resistant Arterial Hypertension.

    PubMed

    Heusser, Karsten; Tank, Jens; Brinkmann, Julia; Menne, Jan; Kaufeld, Jessica; Linnenweber-Held, Silvia; Beige, Joachim; Wilhelmi, Mathias; Diedrich, André; Haller, Hermann; Jordan, Jens

    2016-03-01

    Bilateral bipolar electric carotid sinus stimulation acutely reduced muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in patients with resistant arterial hypertension but is no longer available. The second-generation device uses a smaller unilateral unipolar disk electrode to reduce invasiveness while saving battery life. We hypothesized that the second-generation device acutely lowers BP and MSNA in treatment-resistant hypertensive patients. Eighteen treatment-resistant hypertensive patients (9 women/9 men; 53±11 years; 33±5 kg/m(2)) on stable medications have been included in the study. We monitored finger and brachial BP, heart rate, and MSNA. Without stimulation, BP was 165±31/91±18 mm Hg, heart rate was 75±17 bpm, and MSNA was 48±14 bursts per minute. Acute stimulation with intensities producing side effects that were tolerable in the short term elicited interindividually variable changes in systolic BP (-16.9±15.0 mm Hg; range, 0.0 to -40.8 mm Hg; P=0.002), heart rate (-3.6±3.6 bpm; P=0.004), and MSNA (-2.0±5.8 bursts per minute; P=0.375). Stimulation intensities had to be lowered in 12 patients to avoid side effects at the expense of efficacy (systolic BP, -6.3±7.0 mm Hg; range, 2.8 to -14.5 mm Hg; P=0.028 and heart rate, -1.5±2.3 bpm; P=0.078; comparison against responses with side effects). Reductions in diastolic BP and MSNA (total activity) were correlated (r(2)=0.329; P=0.025). In our patient cohort, unilateral unipolar electric baroreflex stimulation acutely lowered BP. However, side effects may limit efficacy. The approach should be tested in a controlled comparative study. PMID:26831195

  11. Acute Carotid Artery Stent Thrombosis Due to Dual Antiplatelet Resistance

    SciTech Connect

    Köklü, Erkan Arslan, Şakir; Yüksel, İsa Öner; Bayar, Nermin; Koç, Pınar

    2015-08-15

    Carotid artery stenting (CAS) is a revascularization modality that is an alternative to carotid endarterectomy. The efficacy of CAS in primary and secondary prevention from ischemic stroke has been demonstrated in various trials. Acute thrombosis of CAS is a rare complication that can lead to dramatic and catastrophic consequences. We discuss a case of acute CAS thrombosis in a patient who had previously undergone successful CAS. CAS was performed in a 73-year-old man who had had dysarthria lasting 2 weeks with 95 % stenosis in his left internal carotid artery. An acute cerebrovascular event resulting in right-sided hemiplegia developed 24 h after the procedure. Computed tomographic carotid angiography revealed complete occlusion of the stent with thrombus. The cause of stent thrombosis was thought to be antiaggregant resistance to both acetylsalicylic acid and clopidogrel. The most important cause of acute CAS thrombosis is inadequate or ineffective antiaggregant therapy. Evaluating patients who are candidates for CAS for acetylsalicylic acid and clopidogrel resistance may preclude this complication.

  12. Laparoscopic Renal Denervation for Uncontrolled Hypertension Due to Medication Intolerance: A Case Report.

    PubMed

    Gerber, Rebecca C; Bahler, Clint D; Kraus, Michael A; Sundaram, Chandru P

    2016-07-01

    Resistant hypertension is challenging to treat, and most patients with the condition fail to achieve blood pressure control, putting them at increased risk for adverse long-term outcomes. We present the case of a 59-year-old woman with resistant hypertension due to intolerance to nearly all antihypertensive medications. After failure to achieve blood pressure control over a 5-year period, with blood pressures as high as 220/110mmHg, the patient underwent surgical treatment with bilateral laparoscopic renal denervation. Immediately after the procedure, as well as at the 1-, 3-, 9-, and 12-month follow-ups, the patient's blood pressure was reduced to the range of 120-140/80-90mmHg. PMID:26994687

  13. Pseudoaneurysm of the Common Carotid Artery in an Infant due to Swallowed Fish Bone

    PubMed Central

    Jean Roger, Moulion Tapouh; Marcus, Fokou; Emmanuel, Fongang; Boniface, Moifo; Alain Georges, Juimo

    2015-01-01

    Carotid artery pseudoaneurysm is a rare condition, particularly in the paediatric population. Only about 30 cases of carotid artery aneurysms in infants have been published until now. This paper reports the case of a giant pseudoaneurysm of the left common carotid artery due to swallowed fish bone by an 8-year-old boy. This pseudoaneurysm was 5.5 cm transverse-diameter and resulted in severe respiratory distress. It was treated by resection and end-to-end anastomosis with satisfactory outcome after one-year follow-up. To the best of our knowledge, this is the largest carotid artery pseudoaneurysm ever described in children. PMID:26783485

  14. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

    PubMed Central

    Vimaleswaran, Karani S; Cavadino, Alana; Berry, Diane J; Jorde, Rolf; Dieffenbach, Aida Karina; Lu, Chen; Alves, Alexessander Couto; Heerspink, Hiddo J Lambers; Tikkanen, Emmi; Eriksson, Joel; Wong, Andrew; Mangino, Massimo; Jablonski, Kathleen A; Nolte, Ilja M; Houston, Denise K; Ahluwalia, Tarunveer Singh; van der Most, Peter J; Pasko, Dorota; Zgaga, Lina; Thiering, Elisabeth; Vitart, Veronique; Fraser, Ross M; Huffman, Jennifer E; de Boer, Rudolf A; Schöttker, Ben; Saum, Kai-Uwe; McCarthy, Mark I; Dupuis, Josée; Herzig, Karl-Heinz; Sebert, Sylvain; Pouta, Anneli; Laitinen, Jaana; Kleber, Marcus E; Navis, Gerjan; Lorentzon, Mattias; Jameson, Karen; Arden, Nigel; Cooper, Jackie A; Acharya, Jayshree; Hardy, Rebecca; Raitakari, Olli; Ripatti, Samuli; Billings, Liana K; Lahti, Jari; Osmond, Clive; Penninx, Brenda W; Rejnmark, Lars; Lohman, Kurt K; Paternoster, Lavinia; Stolk, Ronald P; Hernandez, Dena G; Byberg, Liisa; Hagström, Emil; Melhus, Håkan; Ingelsson, Erik; Mellström, Dan; Ljunggren, Östen; Tzoulaki, Ioanna; McLachlan, Stela; Theodoratou, Evropi; Tiesler, Carla M T; Jula, Antti; Navarro, Pau; Wright, Alan F; Polasek, Ozren; Hayward, Caroline; Wilson, James F; Rudan, Igor; Salomaa, Veikko; Heinrich, Joachim; Campbell, Harry; Price, Jacqueline F; Karlsson, Magnus; Lind, Lars; Michaëlsson, Karl; Bandinelli, Stefania; Frayling, Timothy M; Hartman, Catharina A; Sørensen, Thorkild I A; Kritchevsky, Stephen B; Langdahl, Bente Lomholt; Eriksson, Johan G; Florez, Jose C; Spector, Tim D; Lehtimäki, Terho; Kuh, Diana; Humphries, Steve E; Cooper, Cyrus; Ohlsson, Claes; März, Winfried; de Borst, Martin H; Kumari, Meena; Kivimaki, Mika; Wang, Thomas J; Power, Chris; Brenner, Hermann; Grimnes, Guri; van der Harst, Pim; Snieder, Harold; Hingorani, Aroon D; Pilz, Stefan; Whittaker, John C; Järvelin, Marjo-Riitta; Hyppönen, Elina

    2015-01-01

    Summary Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97−0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated

  15. Budd-chiari syndrome and renal arterial neurysms due to behcet disease: a rare association

    PubMed Central

    Batur, Abdussamet; Dorum, Meltem; Yüksekkaya, Hasan Ali; Koc, Osman

    2015-01-01

    Behcet's disease is a multisystemic vasculitis of unknown etiology with a chronic relapsing course. Vasculitis in Behcet's disease with predominant vascular involvement is the only vasculitis that affects both arteries and veins of any size. Involvement of the renal artery and inferior vena cava is rare among the arteries and veins, respectively. When disease affect the veins, it is in the form of thrombosis. Arterial complications include aneurysms, stenosis and occlusions. Both rupture of arterial aneurysm and occlusion of suprahepatic veins, causing Budd-Chiari syndrome, are associated with a high mortality rate. Vascular involvement is more common in male patients than in female patients. Men and patients with a younger age of onset present with a more severe prognosis. In this case report, we describe a very rare cause of intrarenal arterial aneurysm's rupture with previous Budd-Chiari syndrome due to Behcet's disease and successful angiographic embolization of actively bleeding aneurysm. PMID:26491527

  16. Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives.

    PubMed

    Chelladurai, Prakash; Seeger, Werner; Pullamsetti, Soni Savai

    2016-06-01

    Pulmonary arterial hypertension (PAH) is a severe and progressive disease, characterised by high pulmonary artery pressure that usually culminates in right heart failure. Recent findings of alterations in the DNA methylation state of superoxide dismutase 2 and granulysin gene loci; histone H1 levels; aberrant expression levels of histone deacetylases and bromodomain-containing protein 4; and dysregulated microRNA networks together suggest the involvement of epigenetics in PAH pathogenesis. Thus, PAH pathogenesis evidently involves the interplay of a predisposed genetic background, epigenetic state and injurious events. Profiling the genome-wide alterations in the epigenetic mechanisms, such as DNA methylation or histone modification pattern in PAH vascular cells, may explain the great variability in susceptibility and disease severity that is frequently associated with pronounced remodelling and worse clinical outcome. Moreover, the influence of genetic predisposition and the acquisition of epigenetic alterations in response to environmental cues in PAH progression and establishment has largely been unexplored on a genome-wide scale. In order to gain insights into the molecular mechanisms leading to the development of PAH and to design novel therapeutic strategies, high-throughput approaches have to be adopted to facilitate systematic identification of the disease-specific networks using next-generation sequencing technologies, the application of these technologies in PAH has been relatively trivial to date. PMID:27246590

  17. Clinical utility of tadalafil in the treatment of pulmonary arterial hypertension: an evidence-based review

    PubMed Central

    Henrie, Adam M; Nawarskas, James J; Anderson, Joe R

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a chronic and disabling condition characterized by an elevated pulmonary vascular resistance and an elevated mean pulmonary arterial pressure. Despite recent improvements in treatment availability, PAH remains challenging to treat, burdensome for patients, and ultimately incurable. Tadalafil is a phos-phodiesterase-5 inhibitor that is administered once daily by mouth for the treatment of PAH. Current treatment guidelines recommend tadalafil as an option for patients with World Health Organization functional class II or III PAH. In a placebo-controlled clinical trial, patients taking tadalafil demonstrated significantly improved exercise capacity as measured by the 6-minute walk distance. Patients also experienced decreased incidence of clinical worsening, increased quality of life, and improved cardiopulmonary hemodynamics. Uncontrolled studies and smaller trials have indicated a possible role for tadalafil as a suitable alternative to sildenafil and as a beneficial add-on option when used in combination with other treatments for PAH. Tadalafil is generally safe and well tolerated. Adverse events are typically mild-to-moderate in intensity, and discontinuation rates are usually low. The purpose of this review is to provide an evidence-based evaluation of the clinical utility of tadalafil in the treatment of PAH. PMID:26587013

  18. Arterial metabolism as studied in vitro by NMR: preliminary results in normotensive and hypertensive aortas.

    PubMed

    Carlier, P G; Grandjean, J; Michel, P; D'Orio, V; Rorive, G L

    1985-12-01

    Arterial tissue has been analysed by 31P-, 13C-, 23Na- and 1H-NMR spectroscopy. Rabbit thoracic aortas were mounted on a system with perfusate circulation and studied in basal conditions. Phosphorus spectra remained stable for hours and showed low levels of phosphocreatine (PCr) compared to skeletal, cardiac or even to nonvascular smooth muscle. Significant levels of sugar-phosphates (SP), phosphodiesters (PDE) were detected, as well as occasionnally a peak in the diphosphodiester region. Experiments with phosphate-free perfusate demonstrated a very low level of intracellular inorganic phosphate. As expected from previous data, free ADP levels in tonic arterial tissue were found much higher than in any other muscle. Addition of norepinephrine into the perfusate induced transient decrease in ATP and PCr levels, associated with an increased production of phosphorylated intermediates. At the early stage of renovascular hypertension, aortic energetic pattern was characterized by an increased ADP/ATP ratio. Natural abundant 13C spectra were recorded from dog aortic fragments and showed mainly resonances attributed to fatty components. After addition of a shift-reagent, dysprosium tripolyphosphate, 23Na-NMR allowed separation of intra- and extracellular Na of perfused rabbits aortas. Proton NMR of lyophilized aortic fragments revealed several peaks originating from biologically relevant molecules, lactate, creatine, taurine... These preliminary data demonstrate the feasability of multinuclear NMR spectroscopy of vascular tissue and are suggestive of the potential of the method when it will be combined with monitoring of functional parameters. PMID:2424380

  19. Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis

    PubMed Central

    Adams, Gregory N.; LaRusch, Gretchen A.; Stavrou, Evi; Zhou, Yihua; Nieman, Marvin T.; Jacobs, Gretta H.; Cui, Yingjie; Lu, Yuan; Jain, Mukesh K.; Mahdi, Fakhri; Shariat-Madar, Zia; Okada, Yoshio; D'Alecy, Louis G.

    2011-01-01

    Prolylcarboxypeptidase (PRCP) activates prekallikrein to plasma kallikrein, leading to bradykinin liberation, and degrades angiotensin II. We now identify PRCP as a regulator of blood vessel homeostasis. β-Galactosidase staining in PRCPgt/gt mice reveals expression in kidney and vasculature. Invasive telemetric monitorings show that PRCPgt/gt mice have significantly elevated blood pressure. PRCPgt/gt mice demonstrate shorter carotid artery occlusion times in 2 models, and their plasmas have increased thrombin generation times. Pharmacologic inhibition of PRCP with Z-Pro-Prolinal or plasma kallikrein with soybean trypsin inhibitor, Pro-Phe-Arg-chloromethylketone or PKSI 527 also shortens carotid artery occlusion times. Aortic and renal tissues have uncoupled eNOS and increased reactive oxygen species (ROS) in PRCPgt/gt mice as detected by dihydroethidium or Amplex Red fluorescence or lucigenin luminescence. The importance of ROS is evidenced by the fact that treatment of PRCPgt/gt mice with antioxidants (mitoTEMPO, apocynin, Tempol) abrogates the hypertensive, prothrombotic phenotype. Mechanistically, our studies reveal that PRCPgt/gt aortas express reduced levels of Kruppel-like factors 2 and 4, thrombomodulin, and eNOS mRNA, suggesting endothelial cell dysfunction. Further, PRCP siRNA treatment of endothelial cells shows increased ROS and uncoupled eNOS and decreased protein C activation because of thrombomodulin inactivation. Collectively, our studies identify PRCP as a novel regulator of vascular ROS and homeostasis. PMID:21297000

  20. Regulation and function of miR-214 in pulmonary arterial hypertension

    PubMed Central

    Deng, Lin; Grant, Jennifer S.; Pinel, Karine; Thomas, Matthew; Morrell, Nicholas W.; MacLean, Margaret R.; Baker, Andrew H.; Denby, Laura

    2016-01-01

    Abstract Dysregulation of microRNAs (miRNAs) can contribute to the etiology of diseases, including pulmonary arterial hypertension (PAH). Here we investigated a potential role for the miR-214 stem loop miRNA and the closely linked miR-199a miRNAs in PAH. All 4 miRNAs were upregulated in the lung and right ventricle (RV) in mice and rats exposed to the Sugen (SU) 5416 hypoxia model of PAH. Further, expression of the miRNAs was increased in pulmonary artery smooth muscle cells exposed to transforming growth factor β1 but not BMP4. We then examined miR-214−/− mice exposed to the SU 5416 hypoxia model of PAH or normoxic conditions and littermate controls. There were no changes in RV systolic pressure or remodeling observed between the miR-214−/− and wild-type hypoxic groups. However, we observed a significant increase in RV hypertrophy (RVH) in hypoxic miR-214−/− male mice compared with controls. Further, we identified that the validated miR-214 target phosphatase and tensin homolog was upregulated in miR-214−/− mice. Thus, miR-214 stem loop loss leads to elevated RVH and may contribute to the heart failure associated with PAH. PMID:27162619

  1. Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension

    PubMed Central

    Long, Lu; Ormiston, Mark L.; Yang, Xudong; Southwood, Mark; Gräf, Stefan; Machado, Rajiv D.; Mueller, Matthias; Kinzel, Bernd; Yung, Lai Ming; Wilkinson, Janine M.; Moore, Stephen D.; Drake, Kylie M.; Aldred, Micheala A.; Yu, Paul; Upton, Paul D.; Morrell, Nicholas W.

    2015-01-01

    Genetic evidence implicates the loss of bone morphogenetic protein type II receptor (BMPR-II) signaling in the endothelium as an initiating factor in pulmonary arterial hypertension (PAH). However, selective targeting of this signaling pathway using BMP ligands has not yet been explored as a therapeutic strategy. We identified BMP9 as the preferred ligand for preventing apoptosis and enhancing monolayer integrity in both pulmonary arterial endothelial cells and blood outgrowth endothelial cells from subjects with PAH bearing mutations in BMPR-II. In vivo, we report the spontaneous generation of PAH in a mouse model bearing a heterozygous knock-in of a human BMPR-II mutation, R899X. Administration of BMP9 reversed established PAH in Bmpr2+/R899X mice, as well as in models of disease developed in response to either monocrotaline or VEGF receptor inhibition combined with chronic hypoxia. These results demonstrate the promise of direct enhancement of endothelial BMP signaling as a novel therapeutic strategy for PAH. PMID:26076038

  2. Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities.

    PubMed

    Farha, Samar; Asosingh, Kewal; Xu, Weiling; Sharp, Jacqueline; George, Deepa; Comhair, Suzy; Park, Margaret; Tang, W H Wilson; Loyd, James E; Theil, Karl; Tubbs, Raymond; Hsi, Eric; Lichtin, Alan; Erzurum, Serpil C

    2011-03-31

    Pulmonary arterial hypertension (PAH) is a proliferative vasculopathy characterized by high circulating CD34(+)CD133(+) proangiogenic progenitors, and endothelial cells that have pathologic expression of hypoxia-inducible factor 1 α (HIF-1α). Here, CD34(+)CD133(+) progenitor cell numbers are shown to be higher in PAH bone marrow, blood, and pulmonary arteries than in healthy controls. The HIF-inducible myeloid-activating factors erythropoietin, stem cell factor (SCF), and hepatocyte growth factor (HGF) are also present at higher than normal levels in PAH blood, and related to disease severity. Primary endothelial cells harvested from human PAH lungs produce greater HGF and progenitor recruitment factor stromal-derived factor 1 α (SDF-1α) than control lung endothelial cells, and thus may contribute to bone marrow activation. Even though PAH patients had normal numbers of circulating blood elements, hematopoietic alterations in myeloid and erythroid lineages and reticulin fibrosis identified a subclinical myeloproliferative process. Unexpectedly, evaluation of bone marrow progenitors and reticulin in nonaffected family members of patients with familial PAH revealed similar myeloid abnormalities. Altogether, the results show that PAH is linked to myeloid abnormalities, some of which may be related to increased production of HIF-inducible factors by diseased pulmonary vasculature, but findings in nonaffected family suggest myeloid abnormalities may be intrinsic to the disease process. PMID:21258008

  3. Hypoxia-inducible factors in human pulmonary arterial hypertension: a link to the intrinsic myeloid abnormalities

    PubMed Central

    Asosingh, Kewal; Xu, Weiling; Sharp, Jacqueline; George, Deepa; Comhair, Suzy; Park, Margaret; Tang, W. H. Wilson; Loyd, James E.; Theil, Karl; Tubbs, Raymond; Hsi, Eric; Lichtin, Alan

    2011-01-01

    Pulmonary arterial hypertension (PAH) is a proliferative vasculopathy characterized by high circulating CD34+CD133+ proangiogenic progenitors, and endothelial cells that have pathologic expression of hypoxia-inducible factor 1 α (HIF-1α). Here, CD34+CD133+ progenitor cell numbers are shown to be higher in PAH bone marrow, blood, and pulmonary arteries than in healthy controls. The HIF-inducible myeloid-activating factors erythropoietin, stem cell factor (SCF), and hepatocyte growth factor (HGF) are also present at higher than normal levels in PAH blood, and related to disease severity. Primary endothelial cells harvested from human PAH lungs produce greater HGF and progenitor recruitment factor stromal-derived factor 1 α (SDF-1α) than control lung endothelial cells, and thus may contribute to bone marrow activation. Even though PAH patients had normal numbers of circulating blood elements, hematopoietic alterations in myeloid and erythroid lineages and reticulin fibrosis identified a subclinical myeloproliferative process. Unexpectedly, evaluation of bone marrow progenitors and reticulin in nonaffected family members of patients with familial PAH revealed similar myeloid abnormalities. Altogether, the results show that PAH is linked to myeloid abnormalities, some of which may be related to increased production of HIF-inducible factors by diseased pulmonary vasculature, but findings in nonaffected family suggest myeloid abnormalities may be intrinsic to the disease process. PMID:21258008

  4. Accuracy of Doppler-Echocardiographic Mean Pulmonary Artery Pressure for Diagnosis of Pulmonary Hypertension

    PubMed Central

    Er, Fikret; Ederer, Stefan; Nia, Amir M.; Caglayan, Evren; Dahlem, Kristina M.; Semmo, Nasser; Gassanov, Natig

    2010-01-01

    Background The validity of Doppler echocardiographic (DE) measurement of systolic pulmonary artery pressure (sPAP) has been questioned. Recent studies suggest that mean pulmonary artery pressure (mPAP) might reflect more accurately the invasive pressures. Methodology/Principal Findings 241 patients were prospectively studied to evaluate the diagnostic accuracy of mPAP for the diagnosis of PH. Right heart catheterization (RHC) and DE were performed in 164 patients mainly for preoperative evaluation of heart valve dysfunction. The correlation between DE and RHC was better when mPAP (r = 0.93) and not sPAP (r = 0.81) was assessed. Bland-Altman analysis revealed a smaller variation of mPAP than sPAP. The following ROC analysis identified that a mPAP≥25.5 mmHg is useful for the diagnosis of PH. This value was validated in an independent cohort of patients (n = 50) with the suspicion of chronic-thromboembolic pulmonary hypertension. The calculated diagnostic accuracy was 98%, based on excellent sensitivity of 98% and specificity of 100%. The corresponding positive and negative predictive values were 100%, respectively 88%. Conclusion mPAP has been found to be highly accurate for the initial diagnosis of PH. A cut-off value of 25.5 mmHg might be helpful to avoid unnecessary RHC and select patients in whom RHC might be beneficial. PMID:21179417

  5. Mechanical characteristics of the pulmonary artery in beagle dogs with hepatopulmonary syndrome and portopulmonary hypertension

    PubMed Central

    YAN, GUOZHEN; HE, JUNFENG; YU, YUELI; LIU, YANG; YUAN, YANFEN; GUO, ZHIYONG

    2016-01-01

    The continuous changes in pulmonary hemodynamic properties in hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) have not been fully characterized in large animal models of HPS and PoPH. Beagle dog models of HPS and PoPH were induced by chronic common bile duct ligation and Sephadex microspheres, respectively. The model was validated by catheter examination and pathological analyses, and the hemodynamic characteristics of the models were observed. The results revealed that the cross-sectional area of the blood vessel was significantly increased in HPS models, but it was significantly decreased in the PoPH models. Furthermore, the resistance of pulmonary circulation was elevated in models of HPS, but it was decreased in models of PoPH. The present findings renew the traditional view that pulmonary hypertension is due to the enhanced peripheral resistance. PMID:26870333

  6. Obesity-related pulmonary arterial hypertension in rats correlates with increased circulating inflammatory cytokines and lipids and with oxidant damage in the arterial wall but not with hypoxia

    PubMed Central

    Irwin, David C.; Garat, Chrystelle V.; Crossno, Joseph T.; MacLean, Paul S.; Sullivan, Timothy M.; Erickson, Paul F.; Jackman, Matthew R.; Harral, Julie W.; Reusch, Jane E. B.

    2014-01-01

    Abstract Obesity is causally linked to a number of comorbidities, including cardiovascular disease, diabetes, renal dysfunction, and cancer. Obesity has also been linked to pulmonary disorders, including pulmonary arterial hypertension (PAH). It was long believed that obesity-related PAH was the result of hypoventilation and hypoxia due to the increased mechanical load of excess body fat. However, in recent years it has been proposed that the metabolic and inflammatory disturbances of obesity may also play a role in the development of PAH. To determine whether PAH develops in obese rats in the absence of hypoxia, we assessed pulmonary hemodynamics and pulmonary artery (PA) structure in the diet-resistant/diet-induced obesity (DR/DIO) and Zucker lean/fatty rat models. We found that high-fat feeding (DR/DIO) or overfeeding (Zucker) elicited PA remodeling, neomuscularization of distal arterioles, and elevated PA pressure, accompanied by right ventricular (RV) hypertrophy. PA thickening and distal neomuscularization were also observed in DIO rats on a low-fat diet. No evidence of hypoventilation or chronic hypoxia was detected in either model, nor was there a correlation between blood glucose or insulin levels and PAH. However, circulating inflammatory cytokine levels were increased with high-fat feeding or calorie overload, and hyperlipidemia and oxidant damage in the PA wall correlated with PAH in the DR/DIO model. We conclude that hyperlipidemia and peripheral inflammation correlate with the development of PAH in obese subjects. Obesity-related inflammation may predispose to PAH even in the absence of hypoxia. PMID:25610600

  7. Anatomical considerations for the development of a new transcatheter aortopulmonary shunt device in patients with severe pulmonary arterial hypertension

    PubMed Central

    2013-01-01

    Abstract Morbidity from pulmonary arterial hypertension (PAH) ensues when the pulmonary pressure reaches suprasystemic levels. A transcatheter alternative to the Potts shunt would allow decompression of the right heart without the surgical risks. To aid development of a transcatheter aortopulmonary shunt (TAPS) device, we described the anatomic relationship between the left