Sample records for induced hypertension pih

  1. A molecular variant of angiotensinogen (M235T) in Korean pregnancy-induced hypertension (PIH) patients

    SciTech Connect

    Kim, Y.T.; Lee, C.; Lim, H.K. [Korea Univ. Anam Hospital, Seoul (Korea, Republic of)

    1994-09-01

    Objective: to illustrate an association between Korean PIH patients and a molecular variant (M235T) in the angiotensinogen gene on chromosome 1q42-43. Material: DNA from peripheral blood of 21 Korean normo-tensive pregnant women and 16 Korean PIH patients. Methods: PCR was performed and the PCR product was digested with Tth111I. The amplification yielded a product of 165 bp. Presence of C at position 704 was identified by cleavage with Tth111I, that generated a fragment of 141 bp. Results: In the PIH group, 2 cases showed 141 bp, 5 cases showed 165 bp, and 9 cases showed both 165 and 141 bp. In the normo-tensive group, 4 cases showed 141 bp, 4 cases showed 165 bp, and 13 cases showed both bands. Conclusion: We could not provide any definite conclusion that the molecular variant (M235T) of angiotensinogen had an association with Korean PIH in this preliminary study. More cases are required to confirm the association between Korean PIH and the molecular variant (M235T) of angiotensinogen.

  2. Placental changes in pregnancy induced hypertension and its impacts on fetal outcome.

    PubMed

    Nahar, L; Nahar, K; Hossain, M I; Yasmin, H; Annur, B M

    2015-01-01

    A descriptive cross sectional study was carried out in the Gynae and Obstetrics & Pathology department of Mymensingh Medical College & Hospital (MMCH) to see the placental changes in normal & pregnancy induced hypertension (PIH) and its impacts on fetus for one year period. Total 80 placentas were collected, 40 from normal pregnant mothers having no hypertension and 40 from PIH group (one from gestational hypertension, 17 from pre-eclampsia and 22 from eclampsia. Macroscopic study of the placenta revealed placental weight, surface area and number of cotyledons were less in study group. Mean placental weight in study group was 419.50gm and in control group was 477.50 (p<0.001). Mean surface area in study group & control group were 232.29cm˛ and 304.80cm˛ respectively (p<0.001). Mean number of cotyledons were 15.39 and 17.40 in study & control group respectively (P<0.001) and lower diameter of umbilical cord (p<0.04667). But in the present study placental thickness was not significant (p<0.539). There was a single umbilical artery present in one patient in PIH group .In PIH group syncytial knots (95%), fibrinoid necrosis (80%), VSM (vasculosyncytial membrane) formation, sclerosis, chorangiosis and calcification were more marked. Infarction was present in placenta of PIH 34(85%) and in control group 8(20%). There was a tendency of lowering the weight of neonate 2.47kg in study group and 3.06kg in control group (p<0.001), number of asphyxiated babies and perinatal morbidity and mortality( still birth was 7.5 and neonatal death was 15%) were more marked in PIH group. In PIH group placental changes were related with fetal outcome. Common placental changes were significant in this study. PMID:25725662

  3. Study of structural changes in placenta in pregnancy-induced hypertension

    PubMed Central

    Salmani, Deepalaxmi; Purushothaman, Suja; Somashekara, Saligrama Chikkannasetty; Gnanagurudasan, Ekambaram; Sumangaladevi, Kampli; Harikishan, Recapu; Venkateshwarareddy, Muthinpala

    2014-01-01

    Background: Hypertension is one of the most common complication during pregnancy. It contributes significantly to maternal and perinatal morbidity and mortality. This study was designed to investigate the morphological and histopathological changes in placenta from pregnancies complicated with hypertension. Objectives: To study the morbid changes in placenta in cases of pregnancy-induced hypertension (PIH) and to correlate the findings with birth weight of new born babies in comparison with normotensive mothers. Materials and Methods: The study was done on 100 placentas, out of which 50 were collected from normotensive mothers and the remaining 50 from PIH cases. All the placentas were studied morphologically and histologically. The birth weight of neonates was recorded. Results: In the present study it was observed that weight and dimensions of placenta was less in study group when compared with control group. The mean neonatal birth weight was more in normal pregnancy and feto-placental weight ratio was significantly high in hypertensive group. Histopathological study showed significant number of syncitial knots, areas of fibrinoid necrosis, hyalinization, calcification, and medial coat proliferation of medium sized blood vessels in hypertensive group. Conclusion: PIH significantly affects the placenta by reducing its weight and dimensions. These changes may cause placental insufficiency as a result of compromised utero-placental blood flow. Therefore has an adverse affect on the neonatal birth weight. PIH has definite influence on morphology, histology of placenta, and thus affects the growth of the fetus. PMID:25097413

  4. Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage\\/dysfunction and activation in pregnancy induced hypertension

    Microsoft Academic Search

    Sunil K Nadar; Eman Al Yemeni; Andrew D Blann; Gregory Y. H Lip

    2004-01-01

    Objective: Endothelial disturbance (whether activation, dysfunction or damage) is a likely pathogenic mechanism in pre-eclampsia and pregnancy-induced hypertension (PIH). We set out to determine which of three plasma markers of endothelial disturbance, indicating endothelial activation (E-selectin) or damage\\/dysfunction (von Willebrand factor (vWf), soluble thrombomodulin), would provide the best discriminator of PIH compared to normotensive pregnancy. Study design: Cross-sectional study of

  5. Pregnancy-Induced Hypertension

    MedlinePLUS

    ... best treatment for me? Will I need bed rest? Will it be necessary to induce labor? Will I need a C-section? What are the risks of early delivery for my baby? Source NHBPEP Report on High Blood Pressure in Pregnancy: A Summary for Family Physicians by MA Zamorski, ...

  6. Drug-induced hypertension: an unappreciated cause of secondary hypertension.

    PubMed

    Grossman, Ehud; Messerli, Franz H

    2012-01-01

    A myriad variety of therapeutic agents or chemical substances can induce either a transient or persistent increase in blood pressure, or interfere with the blood pressure-lowering effects of antihypertensive drugs. Some agents cause either sodium retention or extracellular volume expansion, or activate directly or indirectly the sympathetic nervous system. Other substances act directly on arteriolar smooth muscle or do not have a defined mechanism of action. Some medications that usually lower blood pressure may paradoxically increase blood pressure, or an increase in pressure may be encountered after their discontinuation. In general, drug-induced pressure increases are small and transient: however, severe hypertension involving encephalopathy, stroke, and irreversible renal failure have been reported. The deleterious effect of therapeutic agents is more pronounced in patients with preexisting hypertension, in those with renal failure, and in the elderly. Careful evaluation of a patient's drug regimen may identify chemically induced hypertension and obviate unnecessary evaluation and facilitate antihypertensive therapy. Once chemical-induced hypertension has been identified, discontinuation of the causative agent is recommended, although hypertension can often be managed by specific therapy and dose adjustment if continued use of the offending agent is mandatory. The present review summarizes the therapeutic agents or chemical substances that elevate blood pressure and their mechanisms of action. PMID:22195528

  7. Hypertension induced by liquorice tea.

    PubMed

    Allcock, Emily; Cowdery, James

    2015-01-01

    A 45-year-old woman presented to her general practitioner with a 4-month history of hot flushes, sweating and headaches. On examination, she was found to be hypertensive, and blood tests revealed mild hypokalaemia. While awaiting the results of further investigation into the cause of her elevated blood pressure, the patient conducted her own research and identified liquorice tea as the potential cause of her symptoms. The patient had been drinking up to six cups of liquorice tea per day as a substitute for caffeinated tea and fruit-based infusions. The patient immediately stopped consuming the drink and within 2?weeks her symptoms, hypertension and hypokalaemia had entirely resolved. PMID:26077805

  8. Mechanisms of obesity-induced hypertension

    Microsoft Academic Search

    Vasilios Kotsis; Stella Stabouli; Sofia Papakatsika; Zoe Rizos; Gianfranco Parati

    2010-01-01

    The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle

  9. New developments in the pathogenesis of obesity-induced hypertension.

    PubMed

    Kotsis, Vasilios; Nilsson, Peter; Grassi, Guido; Mancia, Giuseppe; Redon, Josep; Luft, Frank; Schmieder, Roland; Engeli, Stefan; Stabouli, Stella; Antza, Christina; Pall, Denes; Schlaich, Markus; Jordan, Jens

    2015-08-01

    Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential genetic and racial differences or environmental factors that may protect obese patients against the development of hypertension and other co-morbidities. Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of ?-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity. Furthermore, gene-environment interactions may have the potential to modify gene expression and epigenetic mechanisms could also contribute to the heritability of obesity-induced hypertension. Finally, differences in nutrition, gut microbiota, exposure to sun light and exercise may play an important role in the presence or absence of hypertension in obesity. PMID:26103132

  10. Radiation induced heart disease in hypertensive rats

    SciTech Connect

    Lauk, S.; Trott, K.R.

    1988-01-01

    Spontaneously hypertensive Wistar rats were given single doses of X rays to their heart. Irradiation decreased the blood pressure before any myocardial radiation damage was apparent. Male rats, which were more hypertensive than female rats, had a shorter survival time after local heart irradiation than female rats. Antihypertensive treatment with hydralazine did not increase the survival time. It is considered that myocardial hypertrophy is the cause of the increased susceptibility of spontaneously hypertensive rats to local heart irradiation.

  11. Single dose regorafenib-induced hypertensive crisis.

    PubMed

    Yilmaz, B; Kemal, Y; Teker, F; Kut, E; Demirag, G; Yucel, I

    2014-06-01

    Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the gastrointestinal (GI) tract. Regorafenib is a new multikinase inhibitor and is approved for the treatment of GISTs in patients who develop resistance to imatinib and sunitinib. The most common drug-related adverse events with regorafenib are hypertension, hand-foot skin reactions, and diarrhea. Grade IV hypertensive side effect has never been reported after a single dose. In this report, we present a case of Grade IV hypertensive side effect (hypertensive crisis and seizure) after a single dose of regorafenib. A 54-year-old male normotensive GIST patient was admitted to the emergency department with seizure and encephalopathy after the first dosage of regorafenib. His blood pressure was 240/140 mmHg upon admission. After intensive treatment with nitrate and nitroprusside, his blood pressure returned to normal levels in five days. Regorafenib was discontinued, and he did not experience hypertension again. This paper reports the first case of Grade IV hypertension after the first dosage of regorafenib. We can suggest that hypertension is an idiosyncratic side effect unrelated to the dosage. PMID:24980770

  12. Drug-Induced Ocular Hypertension and Angle-Closure Glaucoma.

    PubMed

    Badhu, Badri P; Bhattarai, Balkrishna; Sangraula, Himal P

    2013-01-01

    The objective of this study was to review the available literature on the drugs causing ocular hypertension and glaucoma. Electronic literature search was carried out using the Web sites www.pubmed.gov and www.google.com published through the year 2011. The search words were "drug induced ocular hypertension" and "drug induced glaucoma" used in combination. The articles published or translated into English were studied. Quite a significant number of drugs commonly prescribed by various physicians of different specialties can induce ocular hypertension or glaucoma. A brief account of various drugs that can induce ocular hypertension has been given in this article. Those drugs are parasympatholytics; steroids; anticholinergics, adrenergics, and antidepressants; cholinomimetics; antineoplastic agents; antipsychotic and antiparkinsonism agents; H1 and H2 receptor blockers; botulinum toxin, cardiac agents, and anticoagulants; silicone oil; sulfa drugs; and anesthetic agents. Rational use of these drugs and knowledge of their potential adverse effects can help prevent the devastating complications resulting in loss of vision and compromised quality of life. PMID:26108110

  13. Prolonged Activation of the Baroreflex Abolishes Obesity-Induced Hypertension

    Microsoft Academic Search

    Thomas E. Lohmeier; Terry M. Dwyer; Eric D. Irwin; Martin A. Rossing; Robert S. Kieval

    2007-01-01

    Prolonged electrical activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure in normotensive dogs. The main goal of this study was to assess the influence of prolonged baroreflex activation on arterial pressure and neurohormonal responses in 6 dogs with obesity-induced hypertension. After control measurements, the diet was supplemented with cooked beef fat for 6 weeks,

  14. Lead-induced hypertension. III. Increased hydroxyl radical production

    Microsoft Academic Search

    Yaoxian Ding; Harvey C. Gonick; Nosratola D. Vaziri; Kaihui Liang; Lin Wei

    2001-01-01

    Lead-induced hypertension has previously been shown to be closely associated with an increase in reactive oxygen species in low lead (100 ppm)-treated rats. The present study has attempted to define the specific moiety involved by noting the blood pressure (BP), reactive oxygen species (MDA-TBA), hydroxyl radical, and nitrotyrosine responses to infusion of the reactive oxygen species scavenger dimethylthiourea. Dimethylthiourea, a

  15. Vascular endothelial growth factor affects dendritic cell activity in hypertensive disorders of pregnancy.

    PubMed

    Wang, Jing; Tao, Yu-Mei; Cheng, Xiao-Yan; Zhu, Tian-Feng; Chen, Zhi-Fang; Yao, Hui; Su, Liang-Xiang

    2015-09-01

    Vascular endothelial growth factor (VEGF) activity is involved in the growth and stability of the placenta, and its signaling has been implicated in the development of pregnancy?induced hypertension (PIH). The present study sought to evaluate VEGF levels and dendritic cell (DC) profiles in patients with PIH, and to investigate the effects of VEGF expression on DC phenotypes. The present study assessed 162 patients, 112 of whom were diagnosed with PIH. Serum VEGF was measured by ELISA, while myeloid DC (mDC; (Lin1?HLA?DR+CD11c+) and plasmacytoid DC (pDC; Lin1?HLA?DR+CD123+) counts were determined using flow cytometry. In order to determine the effect of VEGF treatment on DC phenotypes, immature DCs (iDCs) were separated from monocytes by culturing in the presence of cytokines (GM?CSF, IL?4), and then pretreated with VEGF or lipopolysaccharide (LPS). The phenotype of dendritic cells (CD14, CD80, CD83, or CD86) was determined by flow cytometry. The levels of VEGF in the serum of patients with PIH were significantly lower than those in control subjects (P<0.05). The percentage of pDCs found in the serum of patients with preeclampsia was significantly lower than that in the other groups. The percentage of mDCs in the serum of patients with preeclampsia and eclampsia was significantly higher than that in the control and hypertensive disorder groups (P<0.05). The percentage of mDCs was significantly negatively correlated with the levels of VEGF in the preeclamptic and eclamptic patients (r=?0.34 and r=?0.42, respectively; P<0.05). Detected levels of CD80, CD83 and CD86 in DCs treated with VEGF were significant lower than those in DCs treated with LPS alone (P<0.05). In conclusion, abnormal expression of VEGF and an altered dendritic cell profile may be involved in the development of PIH. PMID:25975204

  16. Clinical management of drug-induced hypertension: 2013 Practical Recommendations of the Italian Society of Hypertension (SIIA).

    PubMed

    Virdis, Agostino; Ghiadoni, Lorenzo; Taddei, Stefano

    2014-03-01

    Results from recent observational studies conducted in our country and including approximately 160,000 patients with hypertension, reported that only 37 % of patients achieve effective blood pressure control under treatment. These data confirm that blood pressure control amongst the hypertensive population is still largely unsatisfactory in Italy. For this reason, the Italian Society of Hypertension aims to generate a number of interventions to improve blood pressure control in Italy, including integrated actions with General Practitioners, the implementation of hypertension awareness in the general population, a larger use of home blood pressure measurements, and a survey aimed at identifying all clinical and excellence centers for hypertension diagnosis and treatment throughout the whole national territory. Many therapeutic agents or chemical substances can induce a persistent or transient increase in blood pressure or interfere with the effect of antihypertensive drugs, causing sodium retention and expansion of the extra-cellular volume, activating the sympathetic nervous system and inducing vasoconstriction. This aspect represents one of the most common cause of secondary forms of hypertension, which often is under-evaluated by the physicians. In this review article, the potential causes of secondary forms of hypertension caused by use/abuse of drugs or substances are summarized. PMID:24535939

  17. Mild pregnancy-induced hypertension at term.

    PubMed

    Gant, N F

    1994-04-01

    It was elected to induce labor in Mrs AB after excluding any evidence of severe preeclampsia. Both the fetus and Mrs AB were evaluated. The history, physical examination, and laboratory results were all within normal limits for Mrs AB. Her fetus was appropriately grown for gestational age with an estimated fetal weight of 3,200 g. There was ample but not excessive amniotic fluid noted clinically and by sonography. An amniocentesis to document fetal lung maturation was not done. Two hours after commencing parenteral magnesium sulfate therapy, an oxytocin induction of labor was begun. Fetal well-being was assessed using continuous external electronic monitoring of the fetal heart rate and uterine contractions. Three hours after the induction was started, the cervix was completely effaced and 3 cm dilated. The fetal head was at O station. At this time, the fetal membranes were ruptured and clear amniotic fluid was noted. An internal uterine pressure catheter was inserted, and a fetal scalp electrode applied. The patient received 75 mg of meperidine and 25 mg of promethazine intramuscularly at this time. Five hours after commencing the induction of labor, both mother and fetus were tolerating the labor well. The cervix was 7 cm dilated, and the fetal head was at +2/+5 station. The oxytocin induction was discontinued and another 75 mg dose of meperidine was administered. Blood pressure readings between 150/100 mm Hg and 140/98 mm Hg were recorded throughout labor. Urine output exceeded 150 mL/h. The patient delivered a 3,070-g male infant approximately 9 hours after the start of the induction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8066477

  18. Potential therapeutic targets for hypoxia-induced pulmonary artery hypertension

    PubMed Central

    2014-01-01

    Background Hypoxic pulmonary artery hypertension (PAH) as a severe pulmonary disease is characterized by changes of pulmonary vascular reconstruction. Mitochondrial ATP-sensitive potassium channel (mitoKATP) was considered as one of factors responsible for the proliferation of hypoxic pulmonary arterial smooth muscle cells (PASMCs), although the exact mechanisms remain unclear. Methods Pulmonary artery hypertension was induced in rats with or without 5-hydroxydecanoate (5-HD). The mean pulmonary artery pressure, morphologic changes, mRNA and protein expressions of voltage-gated potassium channels (Kv1.5 channel), were measured. The concentrations of monocyte chemo-attractant protein-1 (MCP-1) and transforming growth factor-beta1 (TGF-?1) were detected. Furthermore, pulmonary arterial smooth muscle cells (PASMCs) were isolated and cultured with or without hypoxia pretreated with or without 5-HD or/and Kv1.5 inhibitor 4-aminopyridine (4-AP). Mitochondrial membrane potential (??m) and the proliferation of PASMCs were detected. Results 5-HD significantly prevented the development of PAH by blocking the mitochondrial membrane depolarization, increased the expression of voltage-gated potassium channels, and reduced pulmonary hypertension mediated by TGF-?1 or MCP-1 signaling pathway. Conclusion The MitoKATP plays an important role in the development of PAH and may be therapeutic target for the treatment of disease. PMID:24507703

  19. Hypertension

    PubMed Central

    LePine, Todd

    2012-01-01

    Hypertension is responsible for roughly one-in-six adult deaths annually in the United States and is associated with five of the top nine causes of death.1 Ten trillion dollars is the estimated annual cost worldwide of the direct and indirect effects of hypertension.2,3 In the U.S. alone, costs estimated at almost $74 billion in 2009 placed a huge economic burden on the health care system.4 The prevalence of hypertension increases with advancing age to the point where more than half of people 60 to 69 years of age and at least three-fourths of those 70 years of age and older are affected.5 Most individuals with hypertension do not have it adequately controlled.1,6 Medication noncompliance due to avoidance of side effects is suggested to be a primary factor.6 The epidemic incidence of hypertension and its significant cost to society indicate that a well-tolerated, cost-effective approach to treatment is urgently needed. PMID:24278815

  20. Role of Proinflammatory Cytokines and Redox Homeostasis in Exercise-Induced Delayed Progression of Hypertension in Spontaneously Hypertensive Rats

    PubMed Central

    Agarwal, Deepmala; Haque, Masudul; Sriramula, Srinivas; Mariappan, Nithya; Pariaut, Romain; Francis, Joseph

    2009-01-01

    Hypertension is a well-known risk factor for various cardiovascular diseases. Recently, exercise has been recommended as a part of lifestyle modification for all hypertensive patients. However, the precise mechanisms of exercise training (ExT)-induced effects on the development of hypertension are poorly understood. Therefore, we hypothesized that chronic ExT would delay the progression of hypertension in young spontaneously hypertensive rats (SHR). In addition, we explored whether the beneficial effects of chronic ExT were mediated by reduced pro-inflammatory cytokines (PICs) and improved redox status. We also investigated the involvement of NF-?B in exercise-induced effects. To test our hypotheses, young normotensive (WKY) and spontaneously hypertensive rats (SHR) were given moderate-intensity ExT for 16 weeks. Blood pressure was determined by the tail-cuff method and cardiac function was assessed by echocardiography. Myocardial total reactive oxygen species (ROS) and superoxide (O2•?) production were measured by electron paramagnetic resonance spectroscopy; TNF-?, IL-1?, gp91phox and iNOS by real-time PCR, and NF-?B activity by EMSA. Chronic ExT in hypertensive rats resulted in significantly reduced blood pressure, reduced concentric hypertrophy and improved diastolic function. ExT significantly reduced PICs, iNOS, attenuated total ROS and O2•? production, and increased antioxidants in SHR. ExT also resulted in increased nitric oxide production and decreased NF-?B activity in SHR. In summary, chronic ExT delays the progression of hypertension and improves cardiac function in young SHR; these ExT-induced beneficial effects are mediated by reduced PICs and improved redox homeostasis via downregulation of NF-?B. PMID:19841289

  1. Cardiovascular effects induced by linalool in normotensive and hypertensive rats.

    PubMed

    Anjos, Paulo J C; Lima, Aline O; Cunha, Patrícia S; De Sousa, Damiăo P; Onofre, Alexandre S C; Ribeiro, Thais P; Medeiros, Isac A; Antoniolli, Angelo R; Quintans-Júnior, Lucindo J; Santosa, Márcio R V

    2013-01-01

    Linalool is a monoterpene alcohol and constituent of several Brazilian aromatic medicinal plants, popularly used against hypertension. Cardiovascular effects induced by linalool were evaluated. In normotensive rats, (+/-)-linalool [1, 5, 10, and 20 mg/kg body weight (BW); intravenous (i.v.)]-induced hypotension was associated with tachycardia, which was attenuated by atropine (2 mg/kg BW) and N(G)-nitro-L-arginine methyl ester (20 mg/kg BW), but was not modified after indomethacin (5 mg/kg BW) administration. In hypertensive rats, linalool [200 mg/kg BW; oral (v.o.)] reduced blood pressure without changing the heart rate. In intact rings of rat mesenteric artery precontracted with 10 microM phenylephrine, linalool (from 6.4 x 10(-6) to 6.4 x 10(-3) M) induced relaxations in a concentration-dependent manner [E(max) = (115 +/- 13)%] that were not changed after atropine administration [E(max) = (105 +/- 2)%], and were not different from those obtained in endothelium-denuded rings precontracted with phenylephrine [E(max) = (108 +/- 7)%] or 80 mM KCl [E(max) = (113 +/- 7)%] or tetraethylammonium incubation [E(max) = (105 +/- 12)%]. Linalool (1.9 x 10(-3) M) antagonized the contractions induced by CaCl2 (3 x 10(-6)-10(-2) M) (maximal inhibition, 81%). Furthermore, linalool inhibited the contractions induced by 10 microM phenylephrine or 20 mM caffeine. In conclusion, these results demonstrate that linalool reduces blood pressure probably due to a direct effect on the vascular smooth muscle leading to vasodilation. PMID:23923614

  2. Hypertension

    Microsoft Academic Search

    Allyn L. Mark; Francois M. Abboud; Gerald F. DiBona; Donald D. Heistad; Larry S. Tobacman; Victor J. Dzau; Carlos Ferrario; Eduardo Marban; Suzanne Oparil; Henry W. Overbeck; Stephen M. Schwartz; Karen Potvin Klein; Connie J. Nelson; John D. Baxter; Kathleen H. Berecek; Edward H. Blaine; Mordecai P. Blaustein; Barry M. Brenner; Michael J. Brody; Hans R. Brunner; Aram V. Chobanian; Robert J. Cody; Allen W. Cowley Jr.; Michael J. Dunn; Alvan R. Feinstein; D. Fink; S. Floras; Ronald H. Freeman; Edward D. Frohlich; Detlev Ganten; Haralambos P. Gavras; Celso E. Gomez-Sanchez; W. Gross; Oregon Willa Hsueh; Tadashi Inagami; I. Johnston; Stevo Julius; Norman M. Kaplan; Paul I. Korner; Theodore A. Kotchen; Eduardo M. Krieger; Brazil Kai Lau; Ronald M. Lauer; Jean-Francois Liard; Marshall D. Lindheimer; Friedrich C. Luft; Giuseppe Mancia; Harry S. Margolius; David A. McCarron; Oregon John; C. McGiff; Trefor O. Morgan; Michael J. Mulvany; Kazuo Murakami; Gary Nicholls; Michael J. Peach; Marc A. Pfeffer; V. Postnov; Morton P. Printz; John P. Rapp; John L. Reid; Donald J. Reis; J. Carlos Romero; E. Safar; A. Guillermo Scicli; T. Shepherd; Thomas Unger; Paul M. Vanhoutte; Stephen F. Vatner; Ronald G. Victor; B. Gunnar Wallin; Gordon H. Williams; Roger R. Williams; Vermont Margaret Foti; Mary Jane Jesse; Clyde E. Johnson; Ben G. Zimmerman

    1992-01-01

    Hypertension is a forum for the presentation of scientific investigation of the highest quality in the broad field of cardiovascular regulation as it may affect high blood pressure research. The editors are interested in receiving original articles that deal with either basic or clinical research in the fields of biochemistry, cellular and molecular biology, immunology, physiology, pharmacology, and epidemiology. In

  3. Effects of Induced Hypertension on Transcranial Doppler Ultrasound Velocities in Patients After Subarachnoid Hemorrhage

    Microsoft Academic Search

    E. M. Manno; D. R. Gress; L. H. Schwamm; M. N. Diringer; C. S. Ogilvy

    Background and Purpose—Transcranial doppler ultrasound (TCD) is used after subarachnoid hemorrhage to detect cerebral vasospasm and is often treated with induced hypertension. Cerebral autoregulation, however, may be disturbed in this population, raising the possibility that TCD velocities may be elevated by induced hypertension. To study this possibility, we performed continuous TCD monitoring of the middle cerebral artery during the induction

  4. Fructose-induced hypertension in rats is concentration- and duration-dependent

    Microsoft Academic Search

    Soter Dai; John H. McNeill

    1995-01-01

    The present study determined the most suitable concentration and duration of fructose treatment for inducing hypertension in Wistar rats. The correlation between fructose-induced hypertension and hyperinsulinemia was also evaluated. The rats were treated with 5%, 10%, or 20% fructose in drinking water. The greatest changes, including increases in blood pressure, fluid intake, and plasma levels of insulin, glucose, and triglycerides,

  5. Activation of Central PPAR-? Attenuates Angiotensin II-Induced Hypertension.

    PubMed

    Yu, Yang; Xue, Bao-Jian; Wei, Shun-Guang; Zhang, Zhi-Hua; Beltz, Terry G; Guo, Fang; Johnson, Alan Kim; Felder, Robert B

    2015-08-01

    Inflammation and renin-angiotensin system activity in the brain contribute to hypertension through effects on fluid intake, vasopressin release, and sympathetic nerve activity. We recently reported that activation of brain peroxisome proliferator-activated receptor (PPAR)-? in heart failure rats reduced inflammation and renin-angiotensin system activity in the hypothalamic paraventricular nucleus and ameliorated the peripheral manifestations of heart failure. We hypothesized that the activation of brain PPAR-? might have beneficial effects in angiotensin II-induced hypertension. Sprague-Dawley rats received a 2-week subcutaneous infusion of angiotensin II (120 ng/kg per minute) combined with a continuous intracerebroventricular infusion of vehicle, the PPAR-? agonist pioglitazone (3 nmol/h) or the PPAR-? antagonist GW9662 (7 nmol/h). Angiotensin II+vehicle rats had increased mean blood pressure, increased sympathetic drive as indicated by the mean blood pressure response to ganglionic blockade, and increased water consumption. PPAR-? mRNA in subfornical organ and hypothalamic paraventricular nucleus was unchanged, but PPAR-? DNA-binding activity was reduced. mRNA for interleukin-1?, tumor necrosis factor-?, cyclooxygenase-2, and angiotensin II type 1 receptor was augmented in both nuclei, and hypothalamic paraventricular nucleus neuronal activity was increased. The plasma vasopressin response to a 6-hour water restriction also increased. These responses to angiotensin II were exacerbated by GW9662 and ameliorated by pioglitazone, which increased PPAR-? mRNA and PPAR-? DNA-binding activity in subfornical organ and hypothalamic paraventricular nucleus. Pioglitazone and GW9662 had no effects on control rats. The results suggest that activating brain PPAR-? to reduce central inflammation and brain renin-angiotensin system activity may be a useful adjunct in the treatment of angiotensin II-dependent hypertension. PMID:26101342

  6. Complement C1q-induced activation of ?-catenin signalling causes hypertensive arterial remodelling

    PubMed Central

    Sumida, Tomokazu; Naito, Atsuhiko T.; Nomura, Seitaro; Nakagawa, Akito; Higo, Tomoaki; Hashimoto, Akihito; Okada, Katsuki; Sakai, Taku; Ito, Masamichi; Yamaguchi, Toshihiro; Oka, Toru; Akazawa, Hiroshi; Lee, Jong-Kook; Minamino, Tohru; Offermanns, Stefan; Noda, Tetsuo; Botto, Marina; Kobayashi, Yoshio; Morita, Hiroyuki; Manabe, Ichiro; Nagai, Toshio; Shiojima, Ichiro; Komuro, Issei

    2015-01-01

    Hypertension induces structural remodelling of arteries, which leads to arteriosclerosis and end-organ damage. Hyperplasia of vascular smooth muscle cells (VSMCs) and infiltration of immune cells are the hallmark of hypertensive arterial remodelling. However, the precise molecular mechanisms of arterial remodelling remain elusive. We have recently reported that complement C1q activates ?-catenin signalling independent of Wnts. Here, we show a critical role of complement C1-induced activation of ?-catenin signalling in hypertensive arterial remodelling. Activation of ?-catenin and proliferation of VSMCs were observed after blood-pressure elevation, which were prevented by genetic and chemical inhibition of ?-catenin signalling. Macrophage depletion and C1qa gene deletion attenuated the hypertension-induced ?-catenin signalling, proliferation of VSMCs and pathological arterial remodelling. Our findings unveil the link between complement C1 and arterial remodelling and suggest that C1-induced activation of ?-catenin signalling becomes a novel therapeutic target to prevent arteriosclerosis in patients with hypertension. PMID:25716000

  7. Exogenous 25-hydroxycholecalciferol does not attenuate salt-induced hypertension.

    PubMed

    Thierry-Palmer, M; Tewolde, T K; Wang, M; Carlyle, K S; Forté, C; Bayorh, M A; Emmett, N L; Williams, E F

    1998-11-01

    We have reported that an inverse relationship exists between blood pressure and plasma concentration of 25-hydroxyvitamin D, the precursor of the hormonal form of vitamin D, for Dahl salt-sensitive rats fed a high salt diet. Plasma 25-hydroxyvitamin D concentrations decreased with time on the diet, as blood pressure increased. Experiments were conducted to determine whether the blood pressure increase of salt-sensitive rats fed a high salt diet could be attenuated by exogenous 25-hydroxycholecalciferol. Dahl salt-sensitive rats were fed a high salt diet and administered exogenous 25-hydroxycholecalciferol via subcutaneously implanted Alzet pumps. Exogenous 25-hydroxycholecalciferol (various doses from 28 to 80 microg/kg body weight-day) had no significant effect on the blood pressure of vitamin D-replete rats fed a high salt diet for 15 days. When exogenous 25-hydroxycholecalciferol (28 and 60 microg/day-kg body weight) was administered to vitamin D-depleted salt-sensitive rats, plasma 25-hydroxyvitamin D concentrations of the rats fed a low salt diet (26 +/- 2 and 59 +/- 6 nM) were proportional to the 25-hydroxycholecalciferol concentration in the pumps. Plasma 25-hydroxyvitamin D concentrations of the rats fed a high salt diet (18 +/- 1 and 23 +/- 3 nM) were not proportional to the 25-hydroxycholecalciferol concentration in the pumps, but were inversely proportional to the blood pressure of the rats. These data indicate no ameliorating effect of exogenous 25-hydroxycholecalciferol on salt-induced hypertension, but accelerated metabolism and/or clearance of 25-hydroxycholecalciferol in salt-induced hypertension. PMID:9879978

  8. The role of constrictor prostanoids in the development of aortic coarctation-induced hypertension in male and female rats

    E-print Network

    Baltzer, Wendy Irene

    2005-02-17

    function and arterial blood pressure (MAP) during development of aortic coarctation-induced hypertension (HT). M and F rats, (15-18 wks.) in four groups: normotensive (NT), hypertensive (HT), ovariectomized (OVX), and OVX estrogen-replaced (OE), underwent...

  9. IgG Receptor Fc?RIIB Plays a Key Role in Obesity-Induced Hypertension

    PubMed Central

    Sundgren, Nathan C.; Vongpatanasin, Wanpen; Boggan, Brigid-Meghan D.; Tanigaki, Keiji; Yuhanna, Ivan S.; Chambliss, Ken L.; Mineo, Chieko; Shaul, Philip W.

    2015-01-01

    There is a well-recognized association between obesity, inflammation, and hypertension. Why obesity causes hypertension is poorly understood. We previously demonstrated using a C-reactive protein (CRP) transgenic mouse that CRP induces hypertension that is related to NO deficiency. Our prior work in cultured endothelial cells identified the Fc? receptor IIB (Fc?RIIB) as the receptor for CRP whereby it antagonizes endothelial NO synthase. Recognizing known associations between CRP and obesity and hypertension in humans, in the present study we tested the hypothesis that Fc?RIIB plays a role in obesity-induced hypertension in mice. Using radiotelemetry, we first demonstrated that the hypertension observed in transgenic mouse-CRP is mediated by the receptor, indicating that Fc?RIIB is capable of modifying blood pressure. We then discovered in a model of diet-induced obesity yielding equal adiposity in all study groups that whereas Fc?RIIB+/+ mice developed obesity-induced hypertension, Fc?RIIB?/? mice were fully protected. Levels of CRP, the related pentraxin serum amyloid P component which is the CRP-equivalent in mice, and total IgG were unaltered by diet-induced obesity; Fc?RIIB expression in endothelium was also unchanged. However, whereas IgG isolated from chow-fed mice had no effect, IgG from high-fat diet–fed mice inhibited endothelial NO synthase in cultured endothelial cells, and this was an Fc?RIIB-dependent process. Thus, we have identified a novel role for Fc?RIIB in the pathogenesis of obesity-induced hypertension, independent of processes regulating adiposity, and it may entail an IgG-induced attenuation of endothelial NO synthase function. Approaches targeting Fc?RIIB may potentially offer new means to treat hypertension in obese individuals. PMID:25368023

  10. Calcitonin Gene-Related Peptide Protects Against Hypertension-Induced Heart and Kidney Damage

    Microsoft Academic Search

    Scott C. Supowit; Arundhati Rao; Mark C. Bowers; Huawei Zhao; Gregory Fink; Barbara Steficek; Parag Patel; Khurshed A. Katki; Donald J. DiPette

    2010-01-01

    Calcitonin gene-related peptide is a potent vasodilator neuropeptide that is localized in perivascular sensory nerves. To determine whether -calcitonin gene-related peptide possesses protective activity against hypertension- induced end organ damage, hypertension was induced in -calcitonin gene-related\\/calcitonin peptide knockout and wild-type mice by uninephrectomy, deoxycorticosteroid administration, and 0.9% saline drinking water. These mice were instrumented previously for long-term telemetric blood pressure

  11. The Stability of the Small Nucleolar Ribonucleoprotein (snoRNP) Assembly Protein Pih1 in Saccharomyces cerevisiae Is Modulated by Its C Terminus*

    PubMed Central

    Paci, Alexandr; Liu, Xiao Hu; Huang, Hao; Lim, Abelyn; Houry, Walid A.; Zhao, Rongmin

    2012-01-01

    Pih1 is an unstable protein and a subunit of the R2TP complex that, in yeast Saccharomyces cerevisiae, also contains the helicases Rvb1, Rvb2, and the Hsp90 cofactor Tah1. Pih1 and the R2TP complex are required for the box C/D small nucleolar ribonucleoprotein (snoRNP) assembly and ribosomal RNA processing. Purified Pih1 tends to aggregate in vitro. Molecular chaperone Hsp90 and its cochaperone Tah1 are required for the stability of Pih1 in vivo. We had shown earlier that the C terminus of Pih1 destabilizes the protein and that the C terminus of Tah1 binds to the Pih1 C terminus to form a stable complex. Here, we analyzed the secondary structure of the Pih1 C terminus and identified two intrinsically disordered regions and five hydrophobic clusters. Site-directed mutagenesis indicated that one predicted intrinsically disordered region IDR2 is involved in Tah1 binding, and that the C terminus of Pih1 contains multiple destabilization or degron elements. Additionally, the Pih1 N-terminal domain, Pih11–230, was found to be able to complement the physiological role of full-length Pih1 at 37 °C. Pih11–230 as well as a shorter Pih1 N-terminal fragment Pih11–195 is able to bind Rvb1/Rvb2 heterocomplex. However, the sequence between the two disordered regions in Pih1 significantly enhances the Pih1 N-terminal domain binding to Rvb1/Rvb2. Based on these data, a model of protein-protein interactions within the R2TP complex is proposed. PMID:23139418

  12. Aging exacerbates hypertension-induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection.

    PubMed

    Toth, Peter; Tarantini, Stefano; Springo, Zsolt; Tucsek, Zsuzsanna; Gautam, Tripti; Giles, Cory B; Wren, Jonathan D; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-06-01

    Recent studies demonstrate that aging exacerbates hypertension-induced cognitive decline, but the specific age-related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension-induced CMHs young (3 months) and aged (24 months) mice were treated with angiotensin II plus L-NAME. We found that the same level of hypertension leads to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Hypertension-induced cerebrovascular oxidative stress and redox-sensitive activation of matrix metalloproteinases (MMPs) were increased in aging. Treatment of aged mice with resveratrol significantly attenuated hypertension-induced oxidative stress, inhibited vascular MMP activation, significantly delayed the onset, and reduced the incidence of CMHs. Collectively, aging promotes CMHs in mice likely by exacerbating hypertension-induced oxidative stress and MMP activation. Therapeutic strategies that reduce microvascular oxidative stress and MMP activation may be useful for the prevention of CMHs, protecting neurocognitive function in high-risk elderly patients. PMID:25677910

  13. Aging exacerbates hypertension-induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection

    PubMed Central

    Toth, Peter; Tarantini, Stefano; Springo, Zsolt; Tucsek, Zsuzsanna; Gautam, Tripti; Giles, Cory B; Wren, Jonathan D; Koller, Akos; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-01-01

    Recent studies demonstrate that aging exacerbates hypertension-induced cognitive decline, but the specific age-related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension-induced CMHs young (3 months) and aged (24 months) mice were treated with angiotensin II plus L-NAME. We found that the same level of hypertension leads to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Hypertension-induced cerebrovascular oxidative stress and redox-sensitive activation of matrix metalloproteinases (MMPs) were increased in aging. Treatment of aged mice with resveratrol significantly attenuated hypertension-induced oxidative stress, inhibited vascular MMP activation, significantly delayed the onset, and reduced the incidence of CMHs. Collectively, aging promotes CMHs in mice likely by exacerbating hypertension-induced oxidative stress and MMP activation. Therapeutic strategies that reduce microvascular oxidative stress and MMP activation may be useful for the prevention of CMHs, protecting neurocognitive function in high-risk elderly patients. PMID:25677910

  14. Hypertension Induces Oxidative Stress but Not Macrophage Infiltration in the Kidney in the Early Stage of Experimental Diabetes Mellitus

    Microsoft Academic Search

    Subrata K. Biswas; Jose B. Lopes de Faria

    2006-01-01

    Background: The combination of diabetes and hypertension increases the incidence and severity of kidney disease in an additive manner. Inflammatory and oxidative stress mechanisms contribute to renal damage in both diabetes and hypertension. Therefore, we investigated whether renal macrophage infiltration and oxidative stress events are additive from the beginning in diabetic animals with coexisting hypertension. Methods: Diabetes was induced in

  15. Angiotensinogen I converting enzyme and angiotensinogen gene polymorphisms are non-randomly distributed in oral contraceptive induced hypertension

    Microsoft Academic Search

    Paolo Mulatero; Franco Rabbia; Stefania Morra di Cella; Cristina Paglieri; Alberto Milan; Leigh Pascoe; Franco Veglio

    2001-01-01

    Objectives and methods: Oral contraceptives (OC) usage increases serum angiotensinogen levels to 3 to 5 times normal and about 5% of these women develop arterial hypertension. The genetic contribution to this susceptibility to OC-induced hypertension is poorly understood. We have analyzed the genotypes of 149 hypertensive and 101 normotensive women using oral contraceptives, for 3 genetic polymorphisms in genes of

  16. Mechanics of Atherosclerosis, Hypertension Induced Growth, and Arterial Remodeling 

    E-print Network

    Hayenga, Heather Naomi

    2012-07-16

    In order to create informed predictive models that capture artery dependent responses during atherosclerosis progression and the long term response to hypertension, one needs to know the structural, biochemical and mechanical ...

  17. Mechanics of Atherosclerosis, Hypertension Induced Growth, and Arterial Remodeling

    E-print Network

    Hayenga, Heather Naomi

    2012-07-16

    In order to create informed predictive models that capture artery dependent responses during atherosclerosis progression and the long term response to hypertension, one needs to know the structural, biochemical and mechanical properties as a...

  18. A dose response relation for noise induced hypertension.

    PubMed Central

    Zhao, Y M; Zhang, S Z; Selvin, S; Spear, R C

    1991-01-01

    The effect of industrial noise on the prevalence of hypertension was studied in a group of 1101 female workers in a textile mill in Beijing in 1985. Essentially the entire group had worked in specific workshops in this mill for all their working lives and all had worked for at least five years. The noise levels within the plant were assessed and appear to have been constant since 1954 resulting in well defined noise exposures for these workers. A cross sectional design was used in which blood pressures were determined and questionnaires administered to the workers over a two month period. As well as demographic information, data were gathered on personal and family history of hypertension, current use of prescription drugs, alcohol, tobacco, and salt in the diet. Logistic regression indicated that exposure to noise is a significant determinant of prevalence of hypertension, but third in order of importance behind family history of hypertension and use of salt. Each of the predictor variables exerted an independent influence on risk of hypertension. Cumulative exposure to noise was not an important dose related variable suggesting that, for those susceptible to the effect, hypertension was manifested within the first five years of exposure. PMID:2015209

  19. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms.

    PubMed

    Hall, John E; do Carmo, Jussara M; da Silva, Alexandre A; Wang, Zhen; Hall, Michael E

    2015-03-13

    Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include (1) physical compression of the kidneys by fat in and around the kidneys, (2) activation of the renin-angiotensin-aldosterone system, and (3) increased sympathetic nervous system activity. Activation of the renin-angiotensin-aldosterone system is likely due, in part, to renal compression, as well as sympathetic nervous system activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for sympathetic nervous system activation in obesity have not been fully elucidated but may require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation. Unless effective antiobesity drugs are developed, the effect of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase. PMID:25767285

  20. Protective effects of estrogen on gender-specific development of diet-induced hypertension

    Microsoft Academic Search

    CHRISTIAN K. ROBERTS; NOSRATOLA D. VAZIRI; R. JAMES BARNARD

    Roberts, Christian K., Nosratola D. Vaziri, and R. James Barnard. Protective effects of estrogen on gender-specific development of diet-induced hypertension. J Appl Physiol 91: 2005-2009, 2001.—Dietary and humoral factors are thought to be involved in the development of hypertension. This study investigated the interaction between diet and gonadal hor- mone status in the development and reversibility of hyper- tension. Normal

  1. Hemodynamic and neurohumoral profile in patients with different types of hypertension in pregnancy.

    PubMed

    Borghi, Claudio; Cicero, Arrigo Francesco Giuseppe; Degli Esposti, Daniela; Immordino, Vincenzo; Bacchelli, Stefano; Rizzo, Nicola; Santi, Francesca; Ambrosioni, Ettore

    2011-06-01

    Hypertension in pregnancy is a frequent disorder that includes a spectrum of conditions. We aimed at comparatively evaluating the hemodynamic, echocardiographic and biohumoral profile of a sample of pregnant Caucasian women with different form of pregnancy-related hypertension. We enrolled 39 non-hypertensive pregnant women (NP), 26 with Chronic HBP in pregnancy (CH), 24 with gestational hypertension (G-PIH), and 33 with pre-eclampsia. We recorded and compared blood pressure (BP), echocardiographic parameters, resting plasma renin activity (PRA) and plasma aldosterone (PA), Plasma levels of atrial (ANP) and brain natriuretic peptide (BNP). PE patients had a significantly higher BP than either G-PIH or NP patients. PE patients had also significantly lower cardiac output than NP, G-PIH and CH. In comparison to NP patients, the total peripheral vascular resistance was 61% higher in PE women and 38% higher in CH patients. All echographic parameters were significantly more altered in PE patients when compared with NP, in respect to any other form of hypertension. Either ANP (+35%) and BNP (+40%) were significantly higher in PE patients than in controls. The PRA was reduced in PE and CH patients when compared either with NP (-38 and -35%, respectively) or G-PIH (-47 and -43%, respectively). On the basis of our data, we can conclude that PE is the gestation associated hypertension with the largest anatomical, functional and biohumoral involvement, and so it has to be involved in a more intensive monitoring and evaluation. PMID:21116739

  2. Effect of veratric acid on the cardiovascular risk of L-NAME-induced hypertensive rats.

    PubMed

    Saravanakumar, Murugesan; Raja, Boobalan

    2012-06-01

    Hypertension is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. This study was undertaken to investigate the effects of veratric acid (VA) on blood pressure, plasma, and tissue lipid profile in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Hypertension was induced in adult male albino rats of Wistar strain, weighing 180-220 g, by oral administration of L-NAME (40 mg/kg) in drinking water for 4 weeks. Rats were treated with VA (40 mg/kg) for 4 weeks. L-NAME-treated rats showed significant increase in mean arterial pressure and heart rate. A significant increase in the concentrations of plasma, tissue (liver and kidney) lipids, and lipoproteins and a significant decrease in the concentration of high-density lipoprotein cholesterol were noticed in L-NAME-induced hypertensive rats. The activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase increased significantly in the liver and kidney, whereas the activities of lipoprotein lipase and lecithin cholesterol acyl transferase were decreased significantly in the plasma of hypertensive rats. Histopathology of liver and kidney and in vitro study also confirmed the biochemical findings of this study. Thus, oral administration of VA reduced hyperlipidemia related to the risk of hypertension. PMID:22361750

  3. Enhanced Development of Azoxymethane-Induced Colonic Preneoplastic Lesions in Hypertensive Rats

    PubMed Central

    Kochi, Takahiro; Shimizu, Masahito; Ohno, Tomohiko; Baba, Atsushi; Sumi, Takafumi; Kubota, Masaya; Shirakami, Yohei; Tsurumi, Hisashi; Tanaka, Takuji; Moriwaki, Hisataka

    2013-01-01

    Metabolic syndrome is associated with an increased risk of colorectal cancer. This study investigated the impact of hypertension, a component of metabolic syndrome, on azoxymethane (AOM)-induced colorectal carcinogenesis using SHRSP/Izm (SHRSP) non-diabetic/hypertensive rats and SHRSP.Z-Leprfa/IzmDmcr (SHRSP-ZF) diabetic/hypertensive rats. Male 6-week-old SHRSP, SHRSP-ZF, and control non-diabetic/normotensive Wister Kyoto/Izm (WKY) rats were given 2 weekly intraperitoneal injections of AOM (20 mg/kg body weight). Two weeks after the last injection of AOM, the SHRSP and SHRSP-ZF rats became hypertensive compared to the control WKY rats. Serum levels of angiotensin-II, the active product of the renin-angiotensin system, were elevated in both SHRSP and SHRSP-ZF rats, but only the SHRSP-ZF rats developed insulin resistance, dyslipidemia, and hyperleptinemia and exhibited an increase in adipose tissue. The development of AOM-induced colonic preneoplastic lesions and aberrant crypts foci, was significantly accelerated in both SHRSP and SHRSP-ZF hypertensive rats, compared to WKY normotensive rats. Furthermore, induction of oxidative stress and exacerbation of inflammation were observed in the colonic mucosa and systemically in SHRSP and SHRSP-ZF rats. Our findings suggest that hypertension plays a role in the early stage of colorectal carcinogenesis by inducing oxidative stress and chronic inflammation, which might be associated with activation of the renin-angiotensin system. PMID:23860206

  4. TJ0711, a novel vasodilatory ?-blocker, protects SHR rats against hypertension induced renal injury

    PubMed Central

    Yang, Juan; Ning, Yong; Qiu, Jun; He, Jin-Seng; Li, Wei; Ma, Zu-Fu; Shao, Ju-Fang; LI, Yue-Qiang; Zeng, Rui; Zhang, Meng; Cheng, Jia; Chen, Su-Fang; Xu, Gang; Wang, Cong-Yi; Yao, Ying

    2013-01-01

    Previous studies suggested that ?-blockers with adjunctive ?1-blocking activities warrant renoprotective function other than the therapeutic effect on hypertension. The current report is designed to dissect the role of TJ0711, a novel ?-blocker with a 1:1 ratio for the ?1/?1 blocking activities, in renoprotection in SHR rats. It was noted that TJ0711 possesses similar potency for control of blood pressure as that of Carvedilol. However, TJ0711 is much more potent in terms of protecting SHR rats against hypertension induced renal injury. Specifically, SHR rats treated with 20mg/kg/day of TJ0711 manifested significantly lower levels for urine albumin and total protein. In line with these result, TJ0711 treated rats displayed much less severe pathological changes in the kidneys. Mechanistic studies revealed that TJ0711 improves kidney perfusion during the course of hypertensive insult by enhancing eNOS expression through suppressing inflammatory cytokine secretion. TJ0711 also attenuates Vasohibin-1 expression to prevent HIF-1? from signal-induced degradation, and by which it promotes HO-1 expression to protect SHR rats against oxidative stress induced by hypertension in the kidneys. Together, our data suggest that TJ0711 possesses higher potency for renoprotection while manifesting the similar effect on hypertension therapy as Carvedilol. PMID:23634239

  5. Differentiating malignant hypertension-induced thrombotic microangiopathy from thrombotic thrombocytopenic purpura

    PubMed Central

    Khanal, Nabin; Dahal, Sumit; Upadhyay, Smrity; Bierman, Philip J.

    2015-01-01

    Objectives: Malignant hypertension can cause thrombotic microangiopathy (TMA) and the overall presentation may mimic thrombotic thrombocytopenic purpura (TTP). This presents a dilemma of whether or not to initiate plasma exchange. The objective of the study was to determine the clinical and laboratory manifestations of malignant hypertension-induced TMA, and its outcomes. Methods: Using several search terms, we reviewed English language articles on malignant hypertension-induced TMA, indexed in MEDLINE by 31 December 2013. We also report a new case. All these cases were analyzed using descriptive statistics. Results: A total of 19 patients, with 10 males, had a median age of 38 years at diagnosis; 58% had a history of hypertension. Mean arterial pressure at presentation was 159?mmHg (range 123–190?mmHg). All had prominent renal dysfunction (mean creatinine of 5.2?mg/dl, range 1.7–13?mg/dl) but relatively modest thrombocytopenia (mean platelet count of 60?×?103/µl, range 12–131?×?103/µl). Reported cases (n?=?9) mostly had preserved ADAMTS-13 activity (mean 64%, range 18–96%). Following blood pressure control, the majority had improvement in presenting symptoms (100%) and platelet counts (84%); however, only 58% had significant improvement in creatinine. More than half (53%) needed hemodialysis. One patient died of cardiac arrest during pacemaker insertion. Conclusion: Prior history of hypertension, high mean arterial pressure, significant renal impairment but relatively modest thrombocytopenia and lack of severe ADAMTS-13 deficiency (activity <10%) at diagnosis are clues to diagnose malignant hypertension-induced TMA. Patients with malignant hypertension respond well to antihypertensive agents and have favorable nonrenal outcomes.

  6. Major inducing factors of hypertensive complications and the interventions required to reduce their prevalence: an epidemiological study of hypertension in a rural population in China

    Microsoft Academic Search

    Min Zhang; Yong Meng; Yongli Yang; Yancai Liu; Caiqin Dong; Jianming Xiao; Ling Zhao; Fang Li

    2011-01-01

    Background  The complications of hypertension cause severe health problems in rural areas in China. We (i) screened the major factors\\u000a inducing hypertensive complications and provided intervention measures; and (ii) verified the efficacy of the New Rural Cooperative\\u000a Medical Scheme (NRCMS; a medical insurance scheme for rural residents) for hypertension management.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  A survey was conducted in the villages of Yunnan (an underdeveloped

  7. Propylene-Glycol-Induced Pulmonary Hypertension in Sheep

    Microsoft Academic Search

    Ronald G. Pearl; Susan A. Rice

    1989-01-01

    Propylene glycol is commonly used as a vehicle for drug administration. In experiments involving the measurement of pulmonary hemodynamics, pentobarbital anesthesia routinely resulted in pulmonary hypertension in sheep. Since pentobarbital is formulated with 40% propylene glycol, we studied the pulmonary hemodynamic effects of propylene glycol in halothane-anesthetized sheep. Intravenous 40% propylene glycol (0.12 ml\\/kg over 3 min) rapidly increased pulmonary

  8. Posterior reversible encephalopathy syndrome from induced hypertension during endovascular thoracoabdominal aortic aneurysm repair.

    PubMed

    Oderich, Gustavo S; Pereira, Alexandre A; Rabinstein, Alejandro A; Mendes, Bernardo C; Pulido, Juan N

    2015-04-01

    Endovascular repair of thoracoabdominal aortic aneurysm has been increasingly performed using fenestrated and branched endografts. Spinal cord injury is a complication of complex endovascular aortic repair, especially in patients with extensive aortic involvement. Maneuvers commonly used to avoid spinal cord injury include cerebrospinal fluid drainage and induced hypertension. Posterior reversible encephalopathy syndrome is associated with abnormal cerebral autoregulation through endothelial and blood-brain barrier dysfunction; the pathophysiology involves vasogenic edema, and severe hypertension is a recognized trigger. We report on a patient who developed posterior reversible encephalopathy syndrome associated with induced hypertension used to prevent spinal cord injury during endovascular repair of a type II thoracoabdominal aortic aneurysm using fenestrated and branched stent grafts. PMID:24365121

  9. [Observations on the deformability of erythrocytes in pregnancy-induced hypertension].

    PubMed

    Ma, F X

    1989-05-01

    By using a model DXC-300 erythrocyte deformability (ED) test apparatus, we determined the indices of filtration (IF) in 34 cases of pregnancy induced hypertension, 27 normal pregnancies and 36 healthy women as control to reflect the deformability of their erythrocyte. The result showed that the IF of hypertensive pregnant women from 37 to 40 weeks was strikingly higher than that in the control and the ED was much less erythrocyte deformability defects the viscosity of blood, the blood flow, and the microcirculation. Therefore, we think that observations on the erythrocyte deformability may be of value in monitoring hydrokinetic and detecting altered microcirculation. ED may be used as a new index for monitoring pregnancy induced hypertension. PMID:2805937

  10. Antihypertensive Effect of Radix Paeoniae Alba in Spontaneously Hypertensive Rats and Excessive Alcohol Intake and High Fat Diet Induced Hypertensive Rats

    PubMed Central

    Su-Hong, Chen; Qi, Chen; Bo, Li; Jian-Li, Gao; Jie, Su; Gui-Yuan, Lv

    2015-01-01

    Radix Paeoniae Alba (Baishao, RPA) has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD-) induced hypertensive rats and spontaneously hypertensive rats (SHR) was constantly received either RPA extract (25 or 75?mg/kg) or captopril (15?mg/kg) all along the experiments. As a result, RPA extract (75?mg/kg) could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT) and aspartate transaminase (AST) in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO) and endothelin (ET) levels. PMID:25784949

  11. Hepatoprotective Effect of Silymarin (Silybum marianum) on Hepatotoxicity Induced by Acetaminophen in Spontaneously Hypertensive Rats

    PubMed Central

    Cardia, Gabriel Fernando Esteves; da Rocha, Bruno Ambrósio; Aguiar, Rafael Pazzinatto; Spironello, Ricardo Alexandre; Caparroz-Assef, Silvana Martins; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

    2015-01-01

    This study was aimed to investigate the effect of Silymarin (SLM) on the hypertension state and the liver function changes induced by acetaminophen (APAP) in spontaneously hypertensive rat (SHR). Animals normotensive (N) or hypertensive (SHR) were treated or not with APAP (3?g/kg, oral) or previously treated with SLM. Twelve hours after APAP administration, plasmatic levels of liver function markers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), gamma glutamyl transferase (?-GT), and alkaline phosphatase (ALP) of all groups, were determined. Liver injury was assessed using histological studies. Samples of their livers were then used to determine the myeloperoxidase (MPO) activity and nitric oxide (NO) production and were also sectioned for histological analysis. No differences were observed for ALT, ?-GT, and GLU levels between SHR and normotensive rats groups. However, AST and ALP levels were increased in hypertensive animals. APAP treatment promoted an increase in ALT and AST in both SHR and N. However, only for SHR, ?-GT levels were increased. The inflammatory response evaluated by MPO activity and NO production showed that SHR was more susceptible to APAP effect, by increasing leucocyte infiltration. Silymarin treatment (Legalon) restored the hepatocyte functional and histopathological alterations induced by APAP in normotensive and hypertensive animals. PMID:25821491

  12. Work-Related Maternal Risk Factors and the Risk of Pregnancy Induced Hypertension and Preeclampsia during Pregnancy. The Generation R Study

    PubMed Central

    Nugteren, Jaap Jan; Snijder, Claudia A.; Hofman, Albert; Jaddoe, Vincent W. V.; Steegers, Eric A. P.; Burdorf, Alex

    2012-01-01

    Objective To study the associations between physically demanding work and occupational exposure to chemicals and hypertensive disorders during pregnancy within a large birth cohort study, the Generation R Study. Methods Associations between occupational characteristics and hypertensive disorders during pregnancy were studied in 4465 pregnant woman participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002–2006). Mothers who filled out a questionnaire during mid-pregnancy (response 77% of enrolment), were included if they conducted paid employment, had a spontaneously conceived singleton live born pregnancy, and did not suffer from pre-existing hypertension (n?=?4465). Questions on physical demanding work were obtained from the Dutch Musculoskeletal Questionnaire and concerned questions on manually handling loads of 25 kg or more, long periods of standing or walking, night shifts, and working hours. To assess occupational exposure to chemicals, job titles and task descriptions were linked to a job-exposure-matrix (JEM), an expert judgment on exposure to chemicals at the workplace. Information on hypertensive disorders during pregnancy was obtained from medical records. Results We observed no consistent associations between any of the work related risk factors, such as long periods of standing or walking, heavy lifting, night shifts, and working hours, nor exposure to chemicals with hypertensive disorders during pregnancy. Conclusion This prospective birth cohort study suggests that there is no association of hypertensive disorders during pregnancy with physically demanding work or exposure to chemicals. However, the low prevalence of PIH and PE, combined with the low prevalence of occupational risk factors limit the power for inference and larger studies are needed to corroborate or refute these findings. PMID:22720087

  13. Calcitonin gene-related peptide protects against hypertension-induced heart and kidney damage.

    PubMed

    Supowit, Scott C; Rao, Arundhati; Bowers, Mark C; Zhao, Huawei; Fink, Gregory; Steficek, Barbara; Patel, Parag; Katki, Khurshed A; Dipette, Donald J

    2005-01-01

    Calcitonin gene-related peptide is a potent vasodilator neuropeptide that is localized in perivascular sensory nerves. To determine whether alpha-calcitonin gene-related peptide possesses protective activity against hypertension-induced end organ damage, hypertension was induced in alpha-calcitonin gene-related/calcitonin peptide knockout and wild-type mice by uninephrectomy, deoxycorticosteroid administration, and 0.9% saline drinking water. These mice were instrumented previously for long-term telemetric blood pressure recording. Control groups were sham-operated and given tap water. Mean arterial pressures were determined, and 3 weeks after initiation of each protocol, tissues were taken for histopathologic studies. The deoxycorticosteroid-salt protocol produced a significant 35% mean arterial pressure increase in both mouse strains. No pathological changes were observed in sections of aortas and femoral arteries from any of the groups studied. Likewise, heart and kidney sections from the hypertensive wild-type mice showed no pathological changes compared with their normotensive counterparts. In contrast, marked vasculitis was seen in the heart sections from the deoxycorticosteroid-salt-treated alpha-calcitonin gene-related peptide knockout mice with thickening and inflammation of the vessel walls. In addition, myocarditis and focal epicarditis with areas of myocardial necrosis were present. Kidneys of these mice exhibited prominent glomerular changes including congestion of the capillary loops, focal mesangial and crescent proliferation, and focal histocytic infiltration. Urinary microalbumin was significantly higher in the hypertensive alpha-calcitonin gene-related peptide knockout compared with hypertensive wild-type mice. These data suggest that deletion of the alpha-calcitonin gene-related peptide gene makes the heart and kidneys more vulnerable to hypertension-induced end organ damage. PMID:15583078

  14. Heme oxygenase-1 mediates the protective effects of rapamycin in monocrotaline-induced pulmonary hypertension

    Microsoft Academic Search

    Hailan Zhou; Hanzhong Liu; Stacy L Porvasnik; Naohiro Terada; Anupam Agarwal; Yanping Cheng; Gary A Visner

    2006-01-01

    Rapamycin inhibits the development and progression of vascular disease. We previously showed that rapamycin induces the cytoprotective protein, heme oxygenase-1 (HO-1), and more importantly, chemically inhibiting HO-1 blocked the antiproliferative actions of rapamycin. In this study, we evaluated whether HO-1 is required for the vascular protective effects of rapamycin in vivo using a rat monocrotaline-induced pulmonary hypertension model. Rats were

  15. Iron restriction inhibits renal injury in aldosterone/salt-induced hypertensive mice.

    PubMed

    Sawada, Hisashi; Naito, Yoshiro; Oboshi, Makiko; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Morisawa, Daisuke; Eguchi, Akiyo; Hirotani, Shinichi; Masuyama, Tohru

    2015-05-01

    Excess iron is associated with the pathogenesis of several renal diseases. Aldosterone is reported to have deleterious effects on the kidney, but there have been no reports of the role of iron in aldosterone/salt-induced renal injury. Therefore, we investigated the effects of dietary iron restriction on the development of hypertension and renal injury in aldosterone/salt-induced hypertensive mice. Ten-week-old male C57BL/6J mice were uninephrectomized and infused with aldosterone for four weeks. These were divided into two groups: one fed a high-salt diet (Aldo) and the other fed a high-salt with iron-restricted diet (Aldo-IR). Vehicle-infused mice without a uninephrectomy were also divided into two groups: one fed a normal diet (control) and the other fed an iron-restricted diet (IR) for 4 weeks. As compared with control and IR mice, Aldo mice showed an increase in both systolic blood pressure and urinary albumin/creatinine ratio, but these increases were reduced in the Aldo-IR group. In addition, renal histology revealed that Aldo mice exhibited glomerulosclerosis and tubulointerstitial fibrosis, whereas these changes were attenuated in Aldo-IR mice. Expression of intracellular iron transport protein transferrin receptor 1 was increased in the renal tubules of Aldo mice compared with control mice. Dietary iron restriction attenuated the development of hypertension and renal injury in aldosterone/salt-induced hypertensive mice. PMID:25693852

  16. Neutrophil Depletion Attenuates Placental Ischemia-Induced Hypertension in the Rat

    PubMed Central

    Regal, Jean F.; Lillegard, Kathryn E.; Bauer, Ashley J.; Elmquist, Barbara J.; Loeks-Johnson, Alex C.; Gilbert, Jeffrey S.

    2015-01-01

    Preeclampsia is characterized by reduced placental perfusion with placental ischemia and hypertension during pregnancy. Preeclamptic women also exhibit a heightened inflammatory state and greater number of neutrophils in the vasculature compared to normal pregnancy. Since neutrophils are associated with tissue injury and inflammation, we hypothesized that neutrophils are critical to placental ischemia-induced hypertension and fetal demise. Using the reduced uteroplacental perfusion pressure (RUPP) model of placental ischemia-induced hypertension in the rat, we determined the effect of neutrophil depletion on blood pressure and fetal resorptions. Neutrophils were depleted with repeated injections of polyclonal rabbit anti-rat polymorphonuclear leukocyte (PMN) antibody (antiPMN). Rats received either antiPMN or normal rabbit serum (Control) on 13.5, 15.5, 17.5, and 18.5 days post conception (dpc). On 14.5 dpc, rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP). On 18.5 dpc, carotid arterial catheters were placed and mean arterial pressure (MAP) was measured on 19.5 dpc. Neutrophil-depleted rats had reduced circulating neutrophils from 14.5 to 19.5 dpc compared to Control, as well as decreased neutrophils in lung and placenta on 19.5 dpc. MAP increased in RUPP Control vs Sham Control rats, and neutrophil depletion attenuated this increase in MAP in RUPP rats without any effect on Sham rats. The RUPP-induced increase in fetal resorptions and complement activation product C3a were not affected by neutrophil depletion. Thus, these data are the first to indicate that neutrophils play an important role in RUPP hypertension and that cells of the innate immune system may significantly contribute to pregnancy-induced hypertension. PMID:26135305

  17. Red wine polyphenols prevent angiotensin II-induced hypertension and endothelial dysfunction in rats: Role of NADPH oxidase

    Microsoft Academic Search

    Mamadou Sarr; Marta Chataigneau; Sandrine Martins; Christa Schott; Jasser El Bedoui; Min-Ho Oak; Bernard Muller; Thierry Chataigneau; Valérie B. Schini-Kerth

    2006-01-01

    Objective: Chronic administration of moderate amounts of red wine has been associated with a protective effect on the cardiovascular system. This study examined whether red wine polyphenols prevent the angiotensin II (Ang II)-induced hypertension and endothelial dysfunction in rats, and, if so, to elucidate the underlying mechanism. Methods: Hypertensive rats were obtained by a 14-day infusion of Ang II. Red

  18. Altered regulation of renal nitric oxide and atrial natriuretic peptide systems in angiotensin II-induced hypertension.

    PubMed

    Bae, Eun Hui; Ma, Seong Kwon; Lee, Jongun; Kim, Soo Wan

    2011-10-10

    The present study was aimed to determine whether there is an altered role of local nitric oxide (NO) and atrial natriuretic peptide (ANP) systems in the kidney in association with the angiotensin (Ang) II-induced hypertension. Male Sprague-Dawley rats were used. Ang II (100 ng·min?ą·kg?ą) was infused through entire time course. Thirteenth day after beginning the regimen, kidneys were taken. The protein expression of NO synthase (NOS) and nitrotyrosine was determined by semiquantitative immunoblotting. The mRNA expression of components of ANP system was determined by real-time polymerase chain reaction. The activities of soluble and particulate guanylyl cyclases were determined by the amount of cGMP generated in responses to sodium nitroprusside and ANP, respectively. There developed hypertension and decreased creatinine clearance in the experimental group. The protein expression of eNOS, nNOS and nitrotyrosine was increased in the cortex, while that of iNOS remained unaltered. The urinary excretion of NO increased in Ang II-induced hypertensive rats. The catalytic activity of soluble guanylyl cyclase was blunted in the glomerulus in Ang II-induced hypertensive rats. The mRNA expression of ANP was increased in Ang II-induced hypertensive rats. Neither the expression of NPR-A nor that of NPR-C was changed. The protein expression of neutral endopeptidase was decreased and the activity of particulate guanylyl cyclase was blunted in the glomerulus and papilla in Ang II-induced hypertensive rats. In conclusion, the synthesis of NO and ANP was increased in the kidney of Ang II-induced hypertension, while stimulated cGMP response was blunted. These results suggest desensitization of guanylyl cyclase in the kidney of Ang II-induced hypertensive rats, which may contribute to the associated renal vasoconstriction and hypertension. PMID:21616096

  19. ?1-Adrenergic blockers exert antioxidant effects, reduce matrix metalloproteinase activity, and improve renovascular hypertension-induced cardiac hypertrophy.

    PubMed

    Rizzi, Elen; Guimaraes, Danielle A; Ceron, Carla S; Prado, Cibele M; Pinheiro, Lucas C; Martins-Oliveira, Alisson; Gerlach, Raquel F; Tanus-Santos, Jose E

    2014-08-01

    Hypertension induces left-ventricular hypertrophy (LVH) by mechanisms involving oxidative stress and unbalanced cardiac matrix metalloproteinase (MMP) activity. We hypothesized that ?1-adrenergic receptor blockers with antioxidant properties (nebivolol) could reverse hypertension-induced LVH more effectively than conventional ?1-blockers (metoprolol) when used at doses that exert similar antihypertensive effects. Two-kidney one-clip (2K1C) hypertension was induced in male Wistar rats. Six weeks after surgery, hypertensive and sham rats were treated with nebivolol (10 mg kg(-1)day(-1)) or metoprolol (20 mg kg(-1)day(-1)) for 4 weeks. Systolic blood pressure was monitored weekly by tail-cuff plethysmography. LV structural changes and fibrosis were studied in hematoxylin/eosin- and picrosirius-stained sections, respectively. Cardiac MMP levels and activity were determined by in situ zymography, gel zymography, and immunofluorescence. Dihydroethidium and lucigenin-derived chemiluminescence assays were used to assess cardiac reactive oxygen species (ROS) production. Nitrotyrosine levels were determined in LV samples by immunohistochemistry and green fluorescence and were evaluated using the ImageJ software. Cardiac protein kinase B/Akt (AKT) phosphorylation state was assessed by Western blot. Both ?-blockers exerted similar antihypertensive effects and attenuated hypertension-induced cardiac remodeling. Both drugs reduced myocyte hypertrophy and collagen deposition in 2K1C rats. These effects were associated with lower cardiac ROS and nitrotyrosine levels and attenuation of hypertension-induced increases in cardiac MMP-2 levels and in situ gelatinolytic activity after treatment with both ?-blockers. Whereas hypertension increased AKT phosphorylation, no effects were found with ?-blockers. In conclusion, we found evidence that two ?1-blockers with different properties attenuate hypertension-induced LV hypertrophy and cardiac collagen deposition in association with significant cardiac antioxidant effects and MMP-2 downregulation, thus suggesting a critical role for ?1-adrenergic receptors in mediating those effects. Nebivolol is not superior to metoprolol, at least with respect to their capacity to reverse hypertension-induced LVH. PMID:24933619

  20. Oxymatrine prevents hypoxia- and monocrotaline-induced pulmonary hypertension in rats.

    PubMed

    Zhang, Bo; Niu, Wen; Xu, Dunquan; Li, Yanyan; Liu, Manling; Wang, Yanxia; Luo, Ying; Zhao, Pengtao; Liu, Yi; Dong, Mingqing; Sun, Rihe; Dong, Haiying; Li, Zhichao

    2014-04-01

    Pulmonary hypertension is a progressive disease characterized by marked pulmonary arterial remodeling and increased vascular resistance. Inflammation and oxidative stress promote the development of pulmonary hypertension. Oxymatrine, one of the main active components of the Chinese herb Sophora flavescens Ait. (Kushen), plays anti-inflammatory and antioxidant protective roles, which effects on pulmonary arteries remain unclear. This study aimed to investigate the effects of oxymatrine on pulmonary hypertension development. Sprague-Dawley rats were exposed to hypoxia for 28 days or injected with monocrotaline, to develop pulmonary hypertension, along with administration of oxymatrine (50mg/kg/day). Hemodynamics and pulmonary arterial remodeling data from the rats were then obtained. The antiproliferative effect of oxymatrine was verified by in vitro assays. The inflammatory cytokine mRNA levels and leukocyte and T cell accumulation in lung tissue were detected. The antioxidative effects of oxymatrine were explored in vitro. Our study shows that oxymatrine treatment attenuated right-ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia or monocrotaline and inhibited proliferation of pulmonary arterial smooth muscle cells (PASMCs). Increased expression of inflammatory cytokine mRNA and accumulation of leukocytes and T cells around the pulmonary arteries were suppressed with oxymatrine administration. Under hypoxic conditions, oxymatrine significantly upregulated Nrf2 and antioxidant protein SOD1 and HO-1 expression, but downregulated hydroperoxide levels in PASMCs. In summary, this study indicates that oxymatrine may prevent pulmonary hypertension through its antiproliferative, anti-inflammatory, and antioxidant effects, thus providing a promising pharmacological avenue for treating pulmonary hypertension. PMID:24440469

  1. The role of estrogen receptors in the contribution of constrictor prostanoids to aortic coarctation-induced hypertension 

    E-print Network

    Sellers, Minga Miown

    2009-05-15

    This study investigated the effects of selective estrogen receptor (ER) agonists on constrictor prostanoid (CP) function and on the development of mean arterial pressure (MAP) in aortic coarctation-induced hypertension (ACIH). Female Sprague...

  2. Etoricoxib attenuates effect of antihypertensives in a rodent model of DOCA-salt induced hypertension.

    PubMed

    Chugh, Preeta Kaur; Gupta, Monica; Agarwal, Monika; Tekur, Uma

    2013-01-01

    While it is known that non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 (COX-2) inhibitors influence BP, the exact relationship and underlying mechanisms are still unclear. We investigated the effect of etoricoxib, a selective COX-2 inhibitor on the antihypertensive efficacy of atenolol; beta-blocker, ramipril; angiotensin converting enzyme inhibitor and telmisartan; angiotensin receptor blocker in deoxycorticosterone acetate (DOCA)-salt hypertensive rats, a mineralocorticoid volume expansion model. Etoricoxib attenuated the antihypertensive-induced reduction of systolic (atenolol; P < .001, ramipril; P = .011, telmisartan; P = .003) and mean arterial pressure (atenolol; P < .001, ramipril; P = .032, telmisartan; P = .023). These results demonstrate that COX-2 dependent mechanisms play a significant role in blood pressure regulation, and etoricoxib-induced COX-2 inhibition blunts the therapeutic effect of different classes of antihypertensives in this mineralocorticoid volume expansion model of hypertension. PMID:23489008

  3. Veratric acid, a phenolic acid attenuates blood pressure and oxidative stress in l-NAME induced hypertensive rats

    Microsoft Academic Search

    Murugesan Saravanakumar; Boobalan Raja

    2011-01-01

    The present study was undertaken to assess the antihypertensive and antioxidant effects of veratric acid on N?-nitro-L arginine methyl ester (l-NAME) induced hypertensive rats. Hypertension was induced in adult male albino rats of the Wistar strain, weighing 180–220g, by oral administration of the l-NAME (40mg\\/kg body weight\\/day) in drinking water for 4weeks. Rats were treated with various doses of veratric

  4. Brain-mediated dysregulation of the bone marrow activity in angiotensin II-induced hypertension.

    PubMed

    Jun, Joo Yun; Zubcevic, Jasenka; Qi, Yanfei; Afzal, Aqeela; Carvajal, Jessica Marulanda; Thinschmidt, Jeffrey S; Grant, Maria B; Mocco, J; Raizada, Mohan K

    2012-11-01

    Oxidative stress in the brain is implicated in increased sympathetic drive, inflammatory status, and vascular dysfunctions, associated with development and establishment of hypertension. However, little is known about the mechanism of this impaired brain-vascular communication. Here, we tested the hypothesis that increased oxidative stress in the brain cardioregulatory areas, such as the paraventricular nucleus of the hypothalamus, is driven by mitochondrial reactive oxygen species and leads to increased inflammatory cells (ICs) and decreased/dysfunctional endothelial progenitor cells (EPCs), thereby compromising vasculature repair and accelerating hypertension. Chronic angiotensin II infusion resulted in elevated blood pressure and sympathetic vasomotor drive, decreased spontaneous baroreflex gain, and increased microglia activation in the paraventricular nucleus. This was associated with 46% decrease in bone marrow (BM)-derived EPCs and 250% increase in BM ICs, resulting in 5-fold decrease of EPC/IC ratio in the BM. Treatment with mitochondrial-targeted antioxidant, a scavenger of mitochondrial O(2)(-·), intracerebroventricularly but not subcutaneously attenuated angiotensin II-induced hypertension, decreased activation of microglia in the paraventricular nucleus, and normalized EPCs/ICs. This functional communication between the brain and BM was confirmed by retrograde neuronal labeling from the BM with green fluorescent protein-tagged pseudorabies virus. Administration of green fluorescent protein-tagged pseudorabies virus into the BM resulted in predominant labeling of paraventricular nucleus neurons within 3 days, with some fluorescence in the nucleus tractus solitarius, the rostral ventrolateral medulla, and subfornical organ. Taken together, these data demonstrate that inhibition of mitochondrial reactive oxygen species attenuates angiotensin II-induced hypertension and corrects the imbalance in EPCs/ICs in the BM. They suggest that an imbalance in vascular reparative and ICs may perpetuate vascular pathophysiology in this model of hypertension. PMID:23045460

  5. Angiotensin II-Induced Hypertension Accelerates the Development of Atherosclerosis in ApoE-Deficient Mice

    Microsoft Academic Search

    Daiana Weiss; John J. Kools; W. Robert Taylor

    2010-01-01

    Background—Angiotensin II may contribute to the development and progression of atherosclerotic lesions because of its growth and proinflammatory effects. We sought to determine whether angiotensin II-induced hypertension would augment and accelerate the development of atherosclerotic lesions in apoE-deficient mice. Methods and Results—Angiotensin II (0.7 mg z kg21 z d21 SC) was administered to apoE-deficient mice via osmotic minipumps. The animals

  6. A high cholesterol\\/cholate diet induced fatty liver in spontaneously hypertensive rats

    Microsoft Academic Search

    Kohji Ueno; Harumi Okuyama

    1986-01-01

    A high cholesterol diet was found to induce fatty liver in spontaneously hypertensive rats. Although cholesterol ester and\\u000a triacylglycerol accumulated in large amounts in liver, the increases of these lipids in plasma were relatively small and no\\u000a increase in cholesterol and cholesterol ester was observed in aorta. In rats fed normal diet, plasma cholesterol ester mainly\\u000a consisted of arachidonate species;

  7. Aortic Connexin43 Is Decreased During Hypertension Induced by Inhibition of Nitric Oxide Synthase

    Microsoft Academic Search

    Jacques-Antoine Haefliger; Paolo Meda; Andrea Formenton; Philippe Wiesel; Anne Zanchi; Hans R. Brunner; Pascal Nicod; Daniel Hayoz

    Connexin43 (Cx43), the predominant gap junction protein in vessels and heart, is involved in the control of cell-to-cell communication and is thought to modulate the contractility of the vascular wall and the electrical coupling of cardiac myocytes. We have investigated the effects of arterial hypertension induced by inhibition of nitric oxide synthase on the expression of Cx43 in aorta and

  8. Treatment of hypertension and renal injury induced by the angiogenesis inhibitor sunitinib: preclinical study.

    PubMed

    Lankhorst, Stephanie; Kappers, Mariëtte H W; van Esch, Joep H M; Smedts, Frank M M; Sleijfer, Stefan; Mathijssen, Ron H J; Baelde, Hans J; Danser, A H Jan; van den Meiracker, Anton H

    2014-12-01

    Common adverse effects of angiogenesis inhibition are hypertension and renal injury. To determine the most optimal way to prevent these adverse effects and to explore their interdependency, the following drugs were investigated in unrestrained Wistar Kyoto rats exposed to the angiogenesis inhibitor sunitinib: the dual endothelin receptor antagonist macitentan; the calcium channel blocker amlodipine; the angiotensin-converting enzyme inhibitor captopril; and the phosphodiesterase type 5 inhibitor sildenafil. Mean arterial pressure was monitored telemetrically. After 8 days, rats were euthanized and blood samples and kidneys were collected. In addition, 24-hour urine samples were collected. After sunitinib start, mean arterial pressure increased rapidly by ?30 mm Hg. Coadministration of macitentan or amlodipine largely prevented this rise, whereas captopril or sildenafil did not. Macitentan, captopril, and sildenafil diminished the sunitinib-induced proteinuria and endothelinuria and glomerular intraepithelial protein deposition, whereas amlodipine did not. Changes in proteinuria and endothelinuria were unrelated. We conclude that in our experimental model, dual endothelin receptor antagonism and calcium channel blockade are suitable to prevent angiogenesis inhibition-induced hypertension, whereas dual endothelin receptor antagonism, angiotensin-converting enzyme inhibitor, and phosphodiesterase type 5 inhibition can prevent angiogenesis inhibition-induced proteinuria. Moreover, the variable response of hypertension and renal injury to different antihypertensive agents suggests that these side effects are, at least in part, unrelated. PMID:25185126

  9. Adrenomedullin alleviates pulmonary artery collagen accumulation in rats with pulmonary hypertension induced by high blood flow.

    PubMed

    Pang, Lulu; Qi, Jianguang; Gao, Yang; Jin, Hongfang; Du, Junbao

    2014-04-01

    Collagen accumulation is one of the important pathologic changes in the development of pulmonary hypertension. Previous research showed that adrenomedullin (ADM) mitigates the development of pulmonary hypertension. The present study explored the role of ADM in the development of pulmonary artery collagen accumulation induced by high pulmonary blood flow, by investigating the effect of ADM [1.5 ?g/(kg h)] subcutaneously administered by mini-osmotic pump on pulmonary hemodynamics, pulmonary vascular structure and pulmonary artery collagen accumulation and synthesis in rats with high pulmonary blood flow induced by aortocaval shunting. The results showed that ADM significantly decreased mean pulmonary artery pressure (mPAP) and the ratio of right ventricular mass to left ventricular plus septal mass [RV/(LV+SP)], attenuated the muscularization of small pulmonary vessels and relative medial thickness (RMT) of pulmonary arteries in rats with high pulmonary blood flow. Meanwhile, ADM ameliorated pulmonary artery collagen deposition represented by a decrease in lung tissue hydroxyproline, collagens I and III content and pulmonary artery collagens I and III expression, reduced collagen synthesis represented by a decrease in lung tissue procollagens I and III mRNA expression. The results suggest that ADM plays a protective role in the development of pulmonary hypertension induced by high blood flow, by inhibiting pulmonary procollagen synthesis and alleviating pulmonary artery collagen accumulation. PMID:24480725

  10. Curcumin Protects against Cadmium-Induced Vascular Dysfunction, Hypertension and Tissue Cadmium Accumulation in Mice

    PubMed Central

    Kukongviriyapan, Upa; Pannangpetch, Patchareewan; Kukongviriyapan, Veerapol; Donpunha, Wanida; Sompamit, Kwanjit; Surawattanawan, Praphassorn

    2014-01-01

    Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd)—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L) in drinking water for eight weeks. Curcumin (50 or 100 mg/kg) was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd. PMID:24662163

  11. Src Family Kinases (SFK) Mediate Angiotensin II-Induced Myosin Light Chain Phosphorylation and Hypertension

    PubMed Central

    Qin, Bo; Zhou, Junlan

    2015-01-01

    Angiotensin (Ang) II is the major bioactive peptide of the renin–angiotensin system (RAS); it contributes to the pathogenesis of hypertension by inducing vascular contraction and adverse remodeling, thus elevated peripheral resistance. Ang II also activates Src family kinases (SFK) in the vascular system, which has been implicated in cell proliferation and migration. However, the role of SFK in Ang II-induced hypertension is largely unknown. In this study, we found that administration of a SFK inhibitor SU6656 markedly lowered the level of systemic BP in Ang II-treated mice, which was associated with an attenuated phosphorylation of the smooth-muscle myosin-light-chain (MLC) in the mesenteric resistant arteries. In the cultured human coronary artery smooth muscle cells (SMCs), pretreatment with SU6656 blocked Ang II-induced MLC phosphorylation and contraction. These results for the first time demonstrate that SFK directly regulate vascular contractile machinery to influence BP. Thus our study provides an additional mechanistic link between Ang II and vasoconstriction via SFK-enhanced MLC phosphorylation in SMCs, and suggests that targeted inhibition of Src may provide a new therapeutic opportunity in the treatment of hypertension. PMID:26011449

  12. Renal angiotensin-converting enzyme is essential for the hypertension induced by nitric oxide synthesis inhibition.

    PubMed

    Giani, Jorge F; Janjulia, Tea; Kamat, Nikhil; Seth, Dale M; Blackwell, Wendell-Lamar B; Shah, Kandarp H; Shen, Xiao Z; Fuchs, Sebastien; Delpire, Eric; Toblli, Jorge E; Bernstein, Kenneth E; McDonough, Alicia A; Gonzalez-Villalobos, Romer A

    2014-12-01

    The kidney is an important source of angiotensin-converting enzyme (ACE) in many species, including humans. However, the specific effects of local ACE on renal function and, by extension, BP control are not completely understood. We previously showed that mice lacking renal ACE, are resistant to the hypertension induced by angiotensin II infusion. Here, we examined the responses of these mice to the low-systemic angiotensin II hypertensive model of nitric oxide synthesis inhibition with L-NAME. In contrast to wild-type mice, mice without renal ACE did not develop hypertension, had lower renal angiotensin II levels, and enhanced natriuresis in response to L-NAME. During L-NAME treatment, the absence of renal ACE was associated with blunted GFR responses; greater reductions in abundance of proximal tubule Na(+)/H(+) exchanger 3, Na(+)/Pi co-transporter 2, phosphorylated Na(+)/K(+)/Cl(-) cotransporter, and phosphorylated Na(+)/Cl(-) cotransporter; and greater reductions in abundance and processing of the ? isoform of the epithelial Na(+) channel. In summary, the presence of ACE in renal tissue facilitates angiotensin II accumulation, GFR reductions, and changes in the expression levels and post-translational modification of sodium transporters that are obligatory for sodium retention and hypertension in response to nitric oxide synthesis inhibition. PMID:25012170

  13. Treatment for hepatitis C virus-induced portal hypertension in leukemic children.

    PubMed

    El-Ashry, Rasha; Malek, Hala Abdel; Ghayaty, Essam A Desoky; El-Gendy, Ahmed A; Darwish, Ahmad; Al-Tonbary, Youssef

    2013-01-01

    Children with acute leukemia are at high risk of hepatitis C infection, either by immunosuppression secondary to chemotherapy or by multiple transfusions of blood products during the course of the disease. Hepatitis C virus (HCV) infection constitutes a major problem during management of acute leukemia due to resultant portal hypertension or bleeding esophageal varices. Chronic HCV infection is a major cause of liver cirrhosis and hepatocellular carcinoma in leukemic survivors. The effect of amlodipine treatment on children with acute lymphoblastic leukemia (ALL) having portal hypertension secondary to HCV infection during maintenance chemotherapy has been studied. Sixty male children (mean age 11.83 ± 1.1 years) with ALL in remission and have HCV infection were included. Diagnosis of HCV infection was confirmed by real-time PCR. Thirty patients received 5 mg amlodipine orally per day for 4 weeks and compared to another 30 patients received placebo therapy and 30 age- and sex-matched children as a control group. Amlodipine significantly reduced the elevated portal blood pressure to normal level in doses which did not interfere with mechanism of action of chemotherapy (p ? 0.001). Treatment with amlodipine can be used to control portal hypertension in leukemic children having HCV-induced portal hypertension. HCV in leukemics could be virtually eliminated by proper testing of the blood transfusion pool. PMID:23553276

  14. Laser-Induced Mouse Model of Chronic Ocular Hypertension

    E-print Network

    Sakaguchi, Donald S.

    an inducible mouse model of glaucoma. METHODS. An obstruction of aqueous humor outflow in adult C57BL6/J mice of all retinal layers. Electron microscopy of optic nerve cross sections re- vealed swelling. 2003;44:4337­4346) DOI: 10.1167/iovs.03-0015 Glaucoma is a progressive optic neuropathy with charac

  15. Intrarenal ghrelin receptor antagonism prevents high-fat diet-induced hypertension in male rats.

    PubMed

    Kemp, Brandon A; Howell, Nancy L; Gildea, John J; Padia, Shetal H

    2014-07-01

    Excess weight gain contributes up to 65% of the risk of primary hypertension, and the increase in blood pressure in response to high-fat diet (HFD) is preceded by significant increases in renal tubular sodium (Na(+)) reabsorption. In normal rats, intrarenal ghrelin infusion increases distal nephron-dependent Na(+) reabsorption via activation of the intrarenal ghrelin receptor (GHSR). This study focusses on the role of intrarenal GHSR-mediated Na(+) reabsorption in HFD-induced hypertension. Dahl salt-sensitive rats received standard diet or HFD for 6 weeks. Rats underwent uninephrectomy and osmotic minipump implantation for chronic intrarenal delivery of vehicle (0.25 ?L/h × 28 d), selective GHSR antagonist [D-Lys-3]-growth hormone releasing peptide-6 (0.2?M/d), or GHSR inverse agonist [D-Arg(1), D-Phe(5), D-Trp(7,9), Leu(11)]-substance P (SUB-P) (3.6?M/d). HFD rats with vehicle pumps had significantly increased renal GHSR expression compared with standard diet (0.092 ± 0.005 vs 0.065 ± 0.004 arbitrary units; P < .05), whereas acyl ghrelin levels were similar (16.3±6.2 vs 15.7±8.7 pg/g tissue). HFD rats with vehicle pumps became hypertensive after 2 weeks (P < .05) and showed a significant reduction in 24-hour urine Na(+) before hypertension. At this time, these rats showed an increase in collecting duct ?-epithelial Na(+) channel, thereby providing a potential mechanism for the excess Na(+) reabsorption. In contrast, HFD rats with [D-Lys-3]-growth hormone releasing peptide-6 or SUB-P pumps never became hypertensive and did not show the reduction in urine Na(+). Because SUB-P blocks the constitutive, but not ghrelin-dependent, activity of the GHSR, and HFD-induced ?-epithelial Na(+) channel up-regulation was abolished during GHSR antagonism, these data suggest that HFD increases the constitutive activity of renal GHSR to increase Na(+) reabsorption and induce hypertension in rats. PMID:24797629

  16. Carbonyl stress induces hypertension and cardio–renal vascular injury in Dahl salt-sensitive rats

    PubMed Central

    Chen, Xianguang; Mori, Takefumi; Guo, Qi; Hu, Chunyan; Ohsaki, Yusuke; Yoneki, Yoshimi; Zhu, Wanjun; Jiang, Yue; Endo, Satoshi; Nakayama, Keisuke; Ogawa, Susumu; Nakayama, Masaaki; Miyata, Toshio; Ito, Sadayoshi

    2013-01-01

    One major precursor of carbonyl stress, methylglyoxal (MG), is elevated in the plasma of chronic kidney disease (CKD) patients, and this precursor contributes to the progression of vascular injury, hypertension and renal injury in diabetic nephropathy patients. This molecule induces salt-sensitive hypertension via a reactive oxygen species-mediated pathway. We examined the role of MG in the pathogenesis of hypertension and cardio–renal injury in Dahl salt-sensitive (Dahl S) rats, which is a rat model of CKD. Nine-week-old Dahl S rats were fed a 1% NaCl diet, and 1% MG was added to their drinking water for up to 12 weeks. Blood pressure and cardio–renal injuries were compared with rats treated with tap water alone. The angiotensin II receptor blocker (ARB), candesartan (10?mg?kg?1?day?1), was administered to MG Dahl S rats to determine the impact of this drug on the pathogenesis of MG-induced CKD. A progressive increase in systolic blood pressure was observed (123±1–148±5?mm?Hg) after 12 weeks of MG administration. MG administration significantly increased urinary albumin excretion, glomerular sclerosis, tubular injury, myocardial collagen content and cardiac perivascular fibrosis. MG also enhanced the renal expression of N?-carboxyethyl-lysine (an advanced glycation end product), 8-hydroxydeoxyguanosine (a marker of oxidative stress), macrophage (ED-1) positive cells (a marker of inflammation) and nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase activity. Candesartan treatment for 4 weeks significantly reduced these parameters. These results suggest that MG-induced hypertension and cardio–renal injury and increased inflammation and carbonyl and oxidative stress, which were partially preventable by an ARB. PMID:23364337

  17. Heme biosynthesis modulation via ?-aminolevulinic acid administration attenuates chronic hypoxia-induced pulmonary hypertension.

    PubMed

    Alhawaj, Raed; Patel, Dhara; Kelly, Melissa R; Sun, Dong; Wolin, Michael S

    2015-04-01

    This study examines how heme biosynthesis modulation with ?-aminolevulinic acid (ALA) potentially functions to prevent 21-day hypoxia (10% oxygen)-induced pulmonary hypertension in mice and the effects of 24-h organoid culture with bovine pulmonary arteries (BPA) with the hypoxia and pulmonary hypertension mediator endothelin-1 (ET-1), with a focus on changes in superoxide and regulation of micro-RNA 204 (miR204) expression by src kinase phosphorylation of signal transducer and activator of transcription-3 (STAT3). The treatment of mice with ALA attenuated pulmonary hypertension (assessed through echo Doppler flow of the pulmonary valve, and direct measurements of right ventricular systolic pressure and right ventricular hypertrophy), increases in pulmonary arterial superoxide (detected by lucigenin), and decreases in lung miR204 and mitochondrial superoxide dismutase (SOD2) expression. ALA treatment of BPA attenuated ET-1-induced increases in mitochondrial superoxide (detected by MitoSox), STAT3 phosphorylation, and decreases in miR204 and SOD2 expression. Because ALA increases BPA protoporphyrin IX (a stimulator of guanylate cyclase) and cGMP-mediated protein kinase G (PKG) activity, the effects of the PKG activator 8-bromo-cGMP were examined and found to also attenuate the ET-1-induced increase in superoxide. ET-1 increased superoxide production and the detection of protoporphyrin IX fluorescence, suggesting oxidant conditions might impair heme biosynthesis by ferrochelatase. However, chronic hypoxia actually increased ferrochelatase activity in mouse pulmonary arteries. Thus, a reversal of factors increasing mitochondrial superoxide and oxidant effects that potentially influence remodeling signaling related to miR204 expression and perhaps iron availability needed for the biosynthesis of heme by the ferrochelatase reaction could be factors in the beneficial actions of ALA in pulmonary hypertension. PMID:25659899

  18. Elevated Endothelial Hypoxia-Inducible Factor-1? Contributes to Glomerular Injury and Promotes Hypertensive Chronic Kidney Disease.

    PubMed

    Luo, Renna; Zhang, Weiru; Zhao, Cheng; Zhang, Yujin; Wu, Hongyu; Jin, Jianping; Zhang, Wenzheng; Grenz, Almut; Eltzschig, Holger K; Tao, Lijian; Kellems, Rodney E; Xia, Yang

    2015-07-01

    Hypertensive chronic kidney disease is one of the most prevalent medical conditions with high morbidity and mortality in the United States and worldwide. However, early events initiating the progression to hypertensive chronic kidney disease are poorly understood. We hypothesized that elevated endothelial hypoxia-inducible factor-1? (HIF-1?) is a common early insult triggering initial glomerular injury leading to hypertensive chronic kidney disease. To test our hypothesis, we used an angiotensin II infusion model of hypertensive chronic kidney disease to determine the specific cell type and mechanisms responsible for elevation of HIF-1? and its role in the progression of hypertensive chronic kidney disease. Genetic studies coupled with reverse transcription polymerase chain reaction profiling revealed that elevated endothelial HIF-1? is essential to initiate glomerular injury and progression to renal fibrosis by the transcriptional activation of genes encoding multiple vasoactive proteins. Mechanistically, we found that endothelial HIF-1? gene expression was induced by angiotensin II in a nuclear factor-?B-dependent manner. Finally, we discovered reciprocal positive transcriptional regulation of endothelial Hif-1? and Nf-?b genes is a key driving force for their persistent activation and disease progression. Overall, our findings revealed that the stimulation of HIF-1? gene expression in endothelial cells is detrimental to induce kidney injury, hypertension, and disease progression. Our findings highlight early diagnostic opportunities and therapeutic approaches for hypertensive chronic kidney disease. PMID:25987665

  19. Effects of tetrahydrobiopterin oral treatment in hypoxia-induced pulmonary hypertension in rat

    PubMed Central

    Francis, Bahaa N.; Hale, Ashley; Channon, Keith M.; Wilkins, Martin R.

    2014-01-01

    Abstract Endothelial nitric oxide synthase (eNOS) plays a major role in maintaining pulmonary vascular homeostasis. Tetrahydrobiopterin (BH4), an essential cofactor that stabilizes the dimerization of eNOS and balances nitric oxide (NO) and superoxide production, may have therapeutic potential in pulmonary hypertension. In the isolated perfused lung, we demonstrated a direct effect of exogenous administration of BH4 on pulmonary NO production, leading to acute vasorelaxation during the plateau phase of hypoxia-induced pulmonary vasoconstriction. In the chronic hypoxia-induced pulmonary hypertension rat model, chronic BH4 oral administration attenuated the pressor response to hypoxia (mean pulmonary artery pressure ± standard error of the mean, 31.8 ± 0.5 mmHg at 100 mg/kg/day; placebo group, 36.3 ± 0.6 mmHg; P < 0.05). During telemetric monitoring, right ventricular systolic pressure was reduced by approximately 50% after 1 week of BH4 treatment at 100 mg/kg/day. BH4 at 100 mg/kg/day reduced right ventricular hypertrophy (from 0.55 ± 0.01 to 0.50 ± 0.01; P < 0.05) and pulmonary vascular muscularization (from 79.2% ± 2% to 65.2% ± 3%; P < 0.01). BH4 treatment enhanced lung eNOS activity and reduced superoxide production, with a net increase in cyclic guanosine monophosphate levels. BH4 is effective in attenuating pulmonary hypertension in the hypoxic rat model when given as a rescue therapy. PMID:25621160

  20. Cardiac arrhythmia mechanisms in rats with heart failure induced by pulmonary hypertension

    PubMed Central

    Benoist, David; Stones, Rachel; Drinkhill, Mark J.; Benson, Alan P.; Yang, Zhaokang; Cassan, Cecile; Gilbert, Stephen H.; Saint, David A.; Cazorla, Olivier; Steele, Derek S.; Bernus, Olivier

    2012-01-01

    Pulmonary hypertension provokes right heart failure and arrhythmias. Better understanding of the mechanisms underlying these arrhythmias is needed to facilitate new therapeutic approaches for the hypertensive, failing right ventricle (RV). The aim of our study was to identify the mechanisms generating arrhythmias in a model of RV failure induced by pulmonary hypertension. Rats were injected with monocrotaline to induce either RV hypertrophy or failure or with saline (control). ECGs were measured in conscious, unrestrained animals by telemetry. In isolated hearts, electrical activity was measured by optical mapping and myofiber orientation by diffusion tensor-MRI. Sarcoplasmic reticular Ca2+ handling was studied in single myocytes. Compared with control animals, the T-wave of the ECG was prolonged and in three of seven heart failure animals, prominent T-wave alternans occurred. Discordant action potential (AP) alternans occurred in isolated failing hearts and Ca2+ transient alternans in failing myocytes. In failing hearts, AP duration and dispersion were increased; conduction velocity and AP restitution were steeper. The latter was intrinsic to failing single myocytes. Failing hearts had greater fiber angle disarray; this correlated with AP duration. Failing myocytes had reduced sarco(endo)plasmic reticular Ca2+-ATPase activity, increased sarcoplasmic reticular Ca2+-release fraction, and increased Ca2+ spark leak. In hypertrophied hearts and myocytes, dysfunctional adaptation had begun, but alternans did not develop. We conclude that increased electrical and structural heterogeneity and dysfunctional sarcoplasmic reticular Ca2+ handling increased the probability of alternans, a proarrhythmic predictor of sudden cardiac death. These mechanisms are potential therapeutic targets for the correction of arrhythmias in hypertensive, failing RVs. PMID:22427523

  1. HNF4alpha Dysfunction as a Molecular Rational for Cyclosporine Induced Hypertension

    PubMed Central

    Niehof, Monika; Borlak, Jürgen

    2011-01-01

    Induction of tolerance against grafted organs is achieved by the immunosuppressive agent cyclosporine, a prominent member of the calcineurin inhibitors. Unfortunately, its lifetime use is associated with hypertension and nephrotoxicity. Several mechanism for cyclosporine induced hypertension have been proposed, i.e. activation of the sympathetic nervous system, endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in prostaglandin and nitric oxide, altered cytosolic calcium translocation, and activation of the renin-angiotensin system (RAS). In this regard the molecular basis for undue RAS activation and an increased signaling of the vasoactive oligopeptide angiotensin II (AngII) remain elusive. Notably, angiotensinogen (AGT) is the precursor of AngII and transcriptional regulation of AGT is controlled by the hepatic nuclear factor HNF4alpha. To better understand the molecular events associated with cyclosporine induced hypertension, we investigated the effect of cyclosporine on HNF4alpha expression and activity and searched for novel HNF4alpha target genes among members of the RAS cascade. Using bioinformatic algorithm and EMSA bandshift assays we identified angiotensin II receptor type 1 (AGTR1), angiotensin I converting enzyme (ACE), and angiotensin I converting enzyme 2 (ACE2) as genes targeted by HNF4alpha. Notably, cyclosporine represses HNF4alpha gene and protein expression and its DNA-binding activity at consensus sequences to AGT, AGTR1, ACE, and ACE2. Consequently, the gene expression of AGT, AGTR1, and ACE2 was significantly reduced as evidenced by quantitative real-time RT-PCR. While RAS is composed of a sophisticated interplay between multiple factors we propose a decrease of ACE2 to enforce AngII signaling via AGTR1 to ultimately result in vasoconstriction and hypertension. Taken collectively we demonstrate cyclosporine to repress HNF4alpha activity through calcineurin inhibitor mediated inhibition of nuclear factor of activation of T-cells (NFAT) which in turn represses HNF4alpha that leads to a disturbed balance of RAS. PMID:21298017

  2. The effects of acute intermittent hypoxia on cardiovascular parameters in normotensive and chronic hypobaric hypoxia-induced hypertensive rabbits.

    PubMed

    Yaman, Muhittin O; Guner, Ibrahim; Uzun, Hafize; Sahin, Gulderen; Yelmen, Nermin

    2014-01-01

    The effects of both chronic hypoxia and acute intermittent hypoxia (AIH) on cardiovascular system are unclear. We designed this study to develop a rabbit model of hypertension by exposure to chronic hypobaric hypoxia (CHH) and to investigate the effects of AIH on hypertensive rabbits. Present study was performed in 13 albino rabbits that divided into CHH and control groups. To develop hypertension, the rabbits were placed in a hypobaric chamber (390 mmHg; 22 hours/day, 30 days). Afterwards, AIH protocol was applied (8% FIO2 (Fraction of Inspired Oxygen) 1 min + 5 min normoxia, 20 cycles, 2 hours) to rabbits anesthetized with urethane and alpha-chloralose. Mean arterial pressure (MAP), heart rate (HR) and hematocrit values have been determined. Also asymmetric dimethylarginine (ADMA), endothelial nitric oxide synthase (eNOS), endothelin-1 and norepinephrine values have been analyzed in blood. We developed a model of hypertension in rabbits via exposure to severe CHH and we believe that ADMA is an important parameter in the development and permanence of CHH-induced hypertension. The main finding of this sudy was the depressor effect of AIH on blood pressure and heart rate in CHH- induced hypertension model. Finally, we believe that AIH protocol may be applicable for prevention and treatment of hypertension if properly developed. PMID:24448370

  3. Pyk2 aggravates hypoxia-induced pulmonary hypertension by activating HIF-1?.

    PubMed

    Fukai, Kuniyoshi; Nakamura, Akihiro; Hoshino, Atsushi; Nakanishi, Naohiko; Okawa, Yoshifumi; Ariyoshi, Makoto; Kaimoto, Satoshi; Uchihashi, Motoki; Ono, Kazunori; Tateishi, Shuhei; Ikeda, Koji; Ogata, Takehiro; Ueyama, Tomomi; Matoba, Satoaki

    2015-04-15

    Pulmonary arterial hypertension (PAH) is a refractory disease characterized by uncontrolled vascular remodeling and elevated pulmonary arterial pressure. Although synthetic inhibitors of some tyrosine kinases have been used to treat PAH, their therapeutic efficacies and safeties remain controversial. Thus, the establishment of novel therapeutic targets based on the molecular pathogenesis underlying PAH is a clinically urgent issue. In the present study, we demonstrated that proline-rich tyrosine kinase 2 (Pyk2), a nonreceptor type protein tyrosine kinase, plays a crucial role in the pathogenesis of pulmonary hypertension (PH) using an animal model of hypoxia-induced PH. Resistance to hypoxia-induced PH was markedly higher in Pyk2-deficient mice than in wild-type mice. Pathological investigations revealed that medial thickening of the pulmonary arterioles, which is a characteristic of hypoxia-induced PH, was absent in Pyk2-deficient mice, suggesting that Pyk2 is involved in the hypoxia-induced aberrant proliferation of vascular smooth muscle cells in hypoxia-induced PH. In vitro experiments using human pulmonary smooth muscle cells showed that hypoxic stress increased the proliferation and migration of cells in a Pyk2-dependent manner. We also demonstrated that Pyk2 plays a crucial role in ROS generation during hypoxic stress and that this Pyk2-dependent generation of ROS is necessary for the activation of hypoxia-inducible factor-1?, a key molecule in the pathogenesis of hypoxia-induced PH. In summary, the results of the present study reveal that Pyk2 plays an important role in the pathogenesis of hypoxia-induced PH. Therefore, Pyk2 may represent a promising therapeutic target for PAH in a clinical setting. PMID:25659487

  4. Hypertension-induced renal fibrosis and spironolactone response vary by rat strain and mineralocorticoid receptor gene expression

    Microsoft Academic Search

    Larisa H. Cavallari; Lucy A. Fashingbauer; Joseph R. Camp; Stephen T. King; David L. Geenen

    IInnttrroodduuccttiioonn.. Aldosterone promotes renal fibrosis via the mineralocorticoid receptor (MR), thus contributing to hypertension-induced nephropathy. We investigated whether MR gene expression influences renal fibrosis and MR antagonist response in a two-kidney, one-clip hypertensive rat model. M Maatteerriiaallss aanndd m meetthhooddss.. Brown Norway (BN), Lewis, and ACI rats were randomised to spironolactone 20 mg\\/kg\\/day or water by gavage, starting four weeks

  5. Does copper enhance the antihypertensive effect of Elaeocarpus ganitrus in experimentally induced hypertensive rats?

    PubMed

    Barve, Kalyani H; Chodankar, Rahul

    2014-04-01

    Ayurveda, one of the traditional systems of medicine of India, reports that the seeds of Elaeocarpus ganitrus Linn. (Tilaceae) can be used for the treatment of hypertension. The main aim is to evaluate the antihypertensive effect of Elaeocarpus ganitrus (Rudraksha) seeds. Powdered seeds were extracted by maceration, overnight, using water, in copper (E1) and glass vessel (E2) and analyzed for antihypertensive activity in cadmium chloride (1 mg/kg intraperitoneally, for a period of 15 days) induced hypertensive male Wistar rats at three dose levels. E1 was administered at the dose of 5, 10, and 15 mg/kg and E2 at dose of 10, 20, and 30 mg/kg. All the data were analyzed using one way analysis of variance (ANOVA) followed by Dunnett's multiple comparison test. E1 and E2 did not show any toxicity at the dose of 5 g/kg in rats. It was found that 15 mg/kg of E1 and 30 mg/kg of E2 decreases the blood pressure by 30.20 mmHg and 28.96 mmHg, respectively, in hypertensive rats. Thus, it can be said that 15 mg/kg of E1 produced similar decrease in blood pressure as was observed with 30 mg/kg of E2. Copper ions in E1 might be additively affecting the reduction in blood pressure with the usage of Elaeocarpus ganitrus extracts. PMID:24948856

  6. Cytosolic phospholipase A2? is critical for angiotensin II-induced hypertension and associated cardiovascular pathophysiology.

    PubMed

    Khan, Nayaab S; Song, Chi Young; Jennings, Brett L; Estes, Anne M; Fang, Xiao R; Bonventre, Joseph V; Malik, Kafait U

    2015-04-01

    Angiotensin II activates cytosolic phospholipase A(2)? (cPLA2?) and releases arachidonic acid from tissue phospholipids, which mediate or modulate ?1 cardiovascular effects of angiotensin II and has been implicated in hypertension. Because arachidonic acid release is the rate limiting step in eicosanoid production, cPLA2? might play a central role in the development of angiotensin II-induced hypertension. To test this hypothesis, we investigated the effect of angiotensin II infusion for 13 days by micro-osmotic pumps on systolic blood pressure and associated pathogenesis in wild type (cPLA2?(+/+)) and cPLA2?(-/-) mice. Angiotensin II-induced increase in systolic blood pressure in cPLA2?(+/+) mice was abolished in cPLA2?(-/-) mice; increased systolic blood pressure was also abolished by the arachidonic acid metabolism inhibitor, 5,8,11,14-eicosatetraynoic acid in cPLA2?(+/+) mice. Angiotensin II in cPLA2?(+/+) mice increased cardiac cPLA2 activity and urinary eicosanoid excretion, decreased cardiac output, caused cardiovascular remodeling with endothelial dysfunction, and increased vascular reactivity in cPLA2?(+/+) mice; these changes were diminished in cPLA2?(-/-) mice. Angiotensin II also increased cardiac infiltration of F4/80(+) macrophages and CD3(+) T lymphocytes, cardiovascular oxidative stress, expression of endoplasmic reticulum stress markers p58(IPK), and CHOP in cPLA2?(+/+) but not cPLA2?(-/-) mice. Angiotensin II increased cardiac activity of ERK1/2 and cSrc in cPLA2?(+/+) but not cPLA2?(-/-) mice. These data suggest that angiotensin II-induced hypertension and associated cardiovascular pathophysiological changes are mediated by cPLA2? activation, most likely through the release of arachidonic acid and generation of eicosanoids with predominant prohypertensive effects and activation of ?1 signaling molecules, including ERK1/2 and cSrc. PMID:25667212

  7. Manganese Porphyrin Reduces Retinal Injury Induced by Ocular Hypertension in Rats

    PubMed Central

    Dogan, Serdar; Unal, Mustafa; Ozturk, Nihal; Yargicoglu, Piraye; Cort, Aysegul; Spasojevic, Ivan; Batinic-Haberle, Ines; Aslan, Mutay

    2011-01-01

    This study aimed to clarify the possible therapeutic benefit of preferential nitric oxide synthase (NOS) inhibition and catalytic antioxidant Mn (III) meso-tetrakis (N-n-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP5+) treatment in a rat model of elevated intraocular pressure (EIOP). Rats were randomly divided into different experimental groups which received either intraperitoneal MnTnHex-2-PyP5+ (0.1 mg/kg/day), intragastric NOS inhibitor (S-methylthiourea: SMT; 5 mg/kg/day) or both agents for a period of 6 weeks. Ocular hypertension was induced by unilaterally cauterizing three episcleral vessels and the unoperated eye served as control. Neuroprotective effects of given treatments were determined via electrophysiological measurements of visual evoked potentials (VEP) while retina and vitreous levels of MnTnHex-2-PyP5+ were measured via LC-MS/MS. Latencies of all VEP components (P1, N1, P2, N2, P3) were significantly prolonged (p<0.05) in EIOP and returned to control levels following all three treatment protocols. Ocular hypertension significantly increased retinal protein nitration (p<0.001) which returned to baseline levels in all treated groups. NOS-2 expression and nitrate/nitrite levels were significantly greater in non-treated rats with EIOP. Retinal TUNEL staining showed apoptosis in all ocular hypertensive rats. The presented data confirm the role of oxidative injury in EIOP and highlight the protective effect of MnTnHex-2-PyP5+ treatment and NOS inhibition in ocular hypertension. PMID:21669199

  8. Cardiovascular disease risk factors after early-onset preeclampsia, late-onset preeclampsia, and pregnancy-induced hypertension.

    PubMed

    Veerbeek, Jan H W; Hermes, Wietske; Breimer, Anath Y; van Rijn, Bas B; Koenen, Steven V; Mol, Ben W; Franx, Arie; de Groot, Christianne J M; Koster, Maria P H

    2015-03-01

    Observational studies have shown an increased lifetime risk of cardiovascular disease (CVD) in women who experienced a hypertensive disorder in pregnancy. This risk is related to the severity of the pregnancy-related hypertensive disease and gestational age at onset. However, it has not been investigated whether these differences in CVD risk factors are already present at postpartum cardiovascular screening. We evaluated postpartum differences in CVD risk factors in 3 subgroups of patients with a history of hypertensive pregnancy. We compared the prevalence of common CVD risk factors postpartum among 448 women with previous early-onset preeclampsia, 76 women with previous late-onset preeclampsia, and 224 women with previous pregnancy-induced hypertension. Women with previous early-onset preeclampsia were compared with women with late-onset preeclampsia and pregnancy-induced hypertension and had significantly higher fasting blood glucose (5.29 versus 4.80 and 4.83 mmol/L), insulin (9.12 versus 6.31 and 6.7 uIU/L), triglycerides (1.32 versus 1.02 and 0.97 mmol/L), and total cholesterol (5.14 versus 4.73 and 4.73 mmol/L). Almost half of the early-onset preeclampsia women had developed hypertension, as opposed to 39% and 25% of women in the pregnancy-induced hypertension and late-onset preeclampsia groups, respectively. Our data show differences in the prevalence of common modifiable CVD risk factors postpartum and suggest that prevention strategies should be stratified according to severity and gestational age of onset for the hypertensive disorders of pregnancy. PMID:25561694

  9. Unaltered caffeine-induced relaxation in the aorta of stroke-prone spontaneously hypertensive rats (SHRSP).

    PubMed

    Sekiguchi, Fumiko; Miyake, Yoshimasa; Kashimoto, Takafumi; Sunano, Satoru

    2002-04-01

    Caffeine-induced relaxation was studied in aortic segments from Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Although acetylcholine-induced endothelium-dependent relaxation was impaired in preparations from SHRSP, the relaxation induced by caffeine was identical in both groups. In addition, caffeine-induced relaxation was not affected by removal of the endothelium in either group. The relaxation induced by N6,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (db-cAMP), a membrane-permeable analog of adenosine 3':5'-cyclic monophosphate (cAMP), was identical in both groups. No significant difference was observed in the increase in cAMP content induced by caffeine in the aortic smooth muscle between the groups, although the basal content was significantly higher in preparations from SHRSP. These results suggest that the relaxation induced by caffeine in these preparations is brought about by its direct effect on smooth muscle and that the response of the smooth muscle to caffeine, including cAMP production, is not altered in preparations from SHRSP compared with those from WKY. PMID:12199529

  10. Aldosterone acting through the central nervous system sensitizes angiotensin II-induced hypertension.

    PubMed

    Xue, Baojian; Zhang, Zhongming; Roncari, Camila F; Guo, Fang; Johnson, Alan Kim

    2012-10-01

    Previous studies have shown that preconditioning rats with a nonpressor dose of angiotensin II (Ang II) sensitizes the pressor response produced by later treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can modulate each other's pressor effects through actions involving the central nervous system. The current studies tested whether Aldo can cross-sensitize the pressor actions of Ang II to enhance hypertension by employing an induction-delay-expression experimental design. Male rats were implanted for telemetered blood pressure recording. During induction, subpressor doses of either subcutaneous or intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for 1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang II was given subcutaneously for 2 weeks (expression). During induction and delay, Aldo had no sustained effect on blood pressure. However, during expression, Ang II-induced hypertension was greater in the groups receiving subcutaneous or intracerebroventricular Aldo during induction in comparison with those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of delay and expression showed increased mRNA expression of several renin-angiotensin-aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca2+]i after Ang II treatment, and there was a greater Fra-like immunoreactivity present at the end of expression in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of Ang II-induced hypertension probably by mechanisms that involve the central nervous system. PMID:22949534

  11. Sodium Nitrite Therapy Rescues Ischemia-Induced Neovascularization and Blood Flow Recovery in Hypertension

    PubMed Central

    Amin, Ali; Choi, Sookyoung; Osman-Elazeik, Yehia; El-Din, Nariman Badr; Kevil, Christopher G.; Navar, Louis G.; Kadowitz, Philip; Trebak, Mohamed; Matrougui, Khalid

    2012-01-01

    Background Arterial hypertension is a major risk factor that can lead to complication of peripheral vascular disease due, in part, to endothelial dysfunction. Because sodium nitrite (SN) can be converted to nitric oxide (NO), which counteracts endothelial dysfunction, we explored the effect of nitrite on neovascularization following hind-limb ischemia in different models of hypertension (HT). Methods and results Chronic delivery of angiotensin-II (Ang-II, 400ng/Kg/min) or N(omega)-nitro-L-arginine-methyl-ester (L-NAME, 0.1g/L) were used for a two week period to induce hypertension. Mice were subjected to femoral artery ligation induced-ischemia in the hind-limb followed by treatment with SN (50mg/L) for 2-weeks. SN significantly reduced systolic arterial blood pressure in mice receiving Ang-II and L-NAME, but had no effect in sham animals. After 2 weeks, blood flow and microangiography showed 60%±1.0 recovery in sham compared to 40%±1.3 in HT mice. Importantly, sham and HT mice treated with SN showed a 100% blood flow recovery associated with normalization in capillary density. The inhibition of xanthine-oxido-reductase (allopurinol) or VEGFR (SU-5416) prevented the neovascularization in HT mice treated with SN. Cyclic GMP (cGMP) content in the hind-limb was significantly increased in mice treated with SN compared to non-treated mice. Nitrite/nitrate content was only increased in the sham group treated with SN. Immunoprecipitation and Western blot analysis revealed an increase in eNOS/Akt/VEGFR phosphorylation in skeletal muscle from mice treated with SN compared to non-treated mice. Conclusion Our findings indicate that SN therapy rescues the neovascularization and blood flow recovery in ischemic hind-limb of sham and HT mice likely through the Akt/NO/cGMP and VEGFR pathways. PMID:23053479

  12. Androgen-induced hypertension in angiotensinogen deficient mice: role of 20-HETE and EETS.

    PubMed

    Garcia, Victor; Cheng, Jennifer; Weidenhammer, Adam; Ding, Yan; Wu, Cheng-Chia; Zhang, Fan; Gotlinger, Katherine; Falck, John R; Schwartzman, Michal L

    2015-01-01

    20-HETE is a potent inducer of endothelial ACE in vitro and administration of lisinopril or losartan attenuates blood pressure in models of 20-HETE-dependent hypertension. The present study was undertaken to further define the relationship between 20-HETE and the renin-angiotensin system in hypertension using an angiotensinogen-deficient mouse (Agt+/-). Treatment of male AGT+/- with 5?-dihydrotestosterone (DHT) increased systolic BP from 102±2 to 125±3mmHg; in comparison, the same treatment raised BP in wild type (WT) from 110±2 to 138±2mmHg. DHT increased vascular 20-HETE levels in AGT+/- and WT from 1.5±0.7 and 2.1±0.6 to 13.0±2.0 and 15.8±4.0ng/mg, respectively. Concurrent treatment with the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented the increases in BP in both AGT+/- and WT mice. Administration of 20-HEDE at the peak of the DHT-induced BP increase (12 days) reduced BP to basal levels after 48h. Interestingly, basal levels of renal microvascular EETs were higher in AGT+/- compared to WT (55.2±9.7 vs 20.0±4.1ng/mg) and treatment of AGT+/- with DHT decreased the levels of EETs (28.4±5.1ng/mg). DHT-mediated changes in vascular EET level were not observed in WT mice. Vascular Cyp4a12 and ACE protein levels were increased in both AGT+/- and WT by 30-40% and decreased with concomitant administration of 20-HEDE. Lisinopril was as effective as 20-HEDE in preventing DHT-mediated increases in BP in both AGT+/- and WT mice. This study substantiates our previous findings that the RAS plays an important role in 20-HETE-mediated hypertension. It also proposes a novel interaction between 20-HETE and EETs. PMID:25526688

  13. Sodium nitrite therapy rescues ischemia-induced neovascularization and blood flow recovery in hypertension.

    PubMed

    Amin, Ali; Choi, Soo-Kyoung; Osman-Elazeik, Yehia; Badr El-Din, Nariman K; Kevil, Christopher G; Navar, Louis G; Kadowitz, Philip; Trebak, Mohamed; Matrougui, Khalid

    2012-12-01

    Arterial hypertension is a major risk factor that can lead to complication of peripheral vascular disease due, in part, to endothelial dysfunction. Because sodium nitrite (SN) can be converted to nitric oxide (NO), which counteracts endothelial dysfunction, we explored the effect of nitrite on neovascularization following hind limb ischemia in different models of hypertension (HT). Chronic delivery of angiotensin II (Ang II, 400 ng/kg/min) or N(omega)-nitro-L-arginine-methyl-ester (L-NAME, 0.1 g/L) was used for a 2-week period to induce hypertension. Mice were subjected to femoral artery ligation-induced ischemia in the hind limb followed by treatment with SN (50 mg/L) for 2 weeks. SN significantly reduced systolic arterial blood pressure in mice receiving Ang II and L-NAME but had no effect in sham animals. After 2 weeks, blood flow and microangiography showed 60 %?±?1.0 recovery in sham compared with 40 %?±?1.3 in HT mice. Importantly, sham and HT mice treated with SN showed a 100 % blood flow recovery associated with normalization in capillary density. The inhibition of xanthine-oxido-reductase (allopurinol) or VEGFR (SU-5416) prevented the neovascularization in HT mice treated with SN. Cyclic GMP (cGMP) content in the hind limb was significantly increased in mice treated with SN compared with non-treated mice. Nitrite/nitrate content was only increased in the sham group treated with SN. Immunoprecipitation and Western blot analysis revealed an increase in eNOS/Akt/VEGFR phosphorylation in skeletal muscle from mice treated with SN compared with non-treated mice. Our findings indicate that SN therapy rescues the neovascularization and blood flow recovery in the ischemic hind limb of sham and HT mice likely through the Akt/NO/cGMP and VEGFR pathways. PMID:23053479

  14. Metalloproteinase Inhibition Protects against Reductions in Circulating Adrenomedullin during Lead-induced Acute Hypertension.

    PubMed

    Nascimento, Regina A; Mendes, Gabryella; Possomato-Vieira, Jose S; Gonçalves-Rizzi, Victor Hugo; Kushima, Hélio; Delella, Flavia K; Dias-Junior, Carlos A

    2015-06-01

    Intoxication with lead (Pb) results in increased blood pressure by mechanisms involving matrix metalloproteinases (MMPs). Recent findings have revealed that MMP type two (MMP-2) seems to cleave vasoactive peptides. This study examined whether MMP-2 and MMP-9 levels/activities increase after acute intoxication with low lead concentrations and whether these changes were associated with increases in blood pressure and circulating endothelin-1 or with reductions in circulating adrenomedullin and calcitonin gene-related peptide (CGRP). Here, we expand previous findings and examine whether doxycycline (a MMPs inhibitor) affects these alterations. Wistar rats received intraperitoneally (i.p.) 1st dose 8 ?g/100 g of lead (or sodium) acetate, a subsequent dose of 0.1 ?g/100 g to cover daily loss and treatment with doxycycline (30 mg/kg/day) or water by gavage for 7 days. Similar whole-blood lead levels (9 ?g/dL) were found in lead-exposed rats treated with either doxycycline or water. Lead-induced increases in systolic blood pressure (from 143 ± 2 to 167 ± 3 mmHg) and gelatin zymography of plasma samples showed that lead increased MMP-9 (but not MMP-2) levels. Both lead-induced increased MMP-9 activity and hypertension were blunted by doxycycline. Doxycycline also prevented lead-induced reductions in circulating adrenomedullin. No significant changes in plasma levels of endothelin-1 or CGRP were found. Lead-induced decreases in nitric oxide markers and antioxidant status were not prevented by doxycycline. In conclusion, acute lead exposure increases blood pressure and MMP-9 activity, which were blunted by doxycycline. These findings suggest that MMP-9 may contribute with lead-induced hypertension by cleaving the vasodilatory peptide adrenomedullin, thereby inhibiting adrenomedullin-dependent lowering of blood pressure. PMID:25308714

  15. Endogenous biosynthesis of arachidonic acid epoxides in humans: Increased formation in pregnancy-induced hypertension

    SciTech Connect

    Catella, F.; Lawson, J.A.; Fitzgerald, D.J.; FitzGerald, G.A. (Vanderbilt Univ., Nashville, TN (USA))

    1990-08-01

    Arachidonic acid is metabolized by means of P450 isoenzyme(s) to form epoxyeicosatrienoic acids (EETs) and their corresponding dihydroxy derivatives (DHETs). In the present study, we established the presence in human urine of 8,9-, 11,12-, and 14,15-EETs and their corresponding DHETs by developing quantitative assays and using negative ion, chemical ionization GC/MS and octadeuterated internal standards. Urinary excretion of 8,9- and 11,12-DHET increased in healthy pregnant women compared with nonpregnant female volunteers. By contrast, excretion of 11,12-DHET and 14,15-DHET, but not the 8,9-DHET regioisomer, increased even further in patients with pregnancy-induced hypertension. Intravenous administration of (3H)14,15-EET to three dogs markedly increased its DHET in plasma. The terminal half-life ranged from 7.9-12.3 min and the volume of distribution (3.5-5.3 liters) suggested limited distribution outside the plasma compartment. Negligible radioactivity was detected in urine; this fact infers that under physiological circumstances, urinary DHETs largely derive from the kidney. That P450 metabolites of arachidonic acid are formed in humans supports the hypothesis that these metabolites contribute to the physiological response to normal pregnancy and the pathophysiology of pregnancy-induced hypertension.

  16. [Role of renal sympathetic nerve and oxidative stress in foot shock-induced hypertension in rats].

    PubMed

    Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Dong, Tao; Zhang, Guo-Xing

    2015-06-25

    The present study was aimed to investigate the roles of renal sympathetic nerve and oxidative stress in the development of foot shock-induced hypertension. Ninety rats were divided into 6 groups (the number of each group was 15): control group, foot shock group, denervation of renal sympathetic nerve group, denervation of renal sympathetic nerve + foot shock group, Tempol treatment + foot shock group, denervation of renal sympathetic nerve + Tempol treatment + foot shock group. Rats were received electrical foot shock for 14 days (2-4 mA, 75 V, shocks of 50-100 ms every 30 s, for 4 h each session through an electrified grid floor every day). Renal sympathetic ablation was used to remove bilateral renal sympathetic nerve in rats (rats were allowed to recover for one week before the beginning of the foot shock procedure). The antioxidant Tempol was injected intraperitoneally at 1 h before foot shock. Systolic blood pressure was measured at 1 h after foot shock on day 0, 3, 7, 10 and 14. Contents of thiobarbituric acid reactive substance (TBARS), renin, angiotensin II (AngII) and glutathione peroxidase (GSH-Px) in plasma were measured by ELISA after 14-day foot shock. The results showed that systolic blood pressure of foot shock group was significantly increased (P < 0.05) compared with that of control group from day 7 to day 14 of foot shock. Denervation of renal sympathetic nerve and/or Tempol treatment significantly reduced the increase of systolic blood pressure induced by foot shock. Levels of TBARS, renin and AngII in plasma were increased significantly in foot shock group compared with that of control group (P < 0.05). Plasma GSH-Px concentration was decreased in foot shock group rats compared with that of control group (P < 0.05). Denervation of renal sympathetic nerve and/or tempol treatment significantly reduced the increase in TBARS, renin, AngII levels induced by foot shock in comparison with that of foot shock group (P < 0.05), but had no effects on the reduction of GSH-Px concentration. The results suggest that renal sympathetic nerve may play an important role in the development of foot shock-induced hypertension, and renal sympathetic nerve may influence oxidative stress and directly or indirectly activate renin-angiotensin-aldosterone system, so the foot shock-induced high blood pressure may be maintained and hypertension may therefore be produced. PMID:26109307

  17. Caffeine intake improves fructose-induced hypertension and insulin resistance by enhancing central insulin signaling.

    PubMed

    Yeh, Tung-Chen; Liu, Chun-Peng; Cheng, Wen-Han; Chen, Bo-Rong; Lu, Pei-Jung; Cheng, Pei-Wen; Ho, Wen-Yu; Sun, Gwo-Ching; Liou, Jau-Cheng; Tseng, Ching-Jiunn

    2014-03-01

    Recent clinical studies found that fructose intake leads to insulin resistance and hypertension. Fructose consumption promotes protein fructosylation and formation of superoxide. In a previous study, we revealed that inhibition of superoxide production in the nucleus tractus solitarii (NTS) reduces blood pressure. Caffeine displays significant antioxidant ability in protecting membranes against oxidative damage and can lower the risk of insulin resistance. However, the mechanism through which caffeine improves fructose-induced insulin resistance is unclear. The aim of this study was to investigate whether caffeine consumption can abolish superoxide generation to enhance insulin signaling in the NTS, thereby reducing blood pressure in rats with fructose-induced hypertension. Treatment with caffeine for 4 weeks decreased blood pressure, serum fasting glucose, insulin, homeostatic model assessment-insulin resistance, and triglyceride levels and increased the serum direct high-density lipoprotein level in fructose-fed rats but not in control rats. Caffeine treatment resulted in the recovery of fructose-induced decrease in nitric oxide production in the NTS. Immunoblotting and immunofluorescence analyses further showed that caffeine reduced the fructose-induced phosphorylation of insulin receptor substrate 1 (IRS1(S307)) and reversed Akt(S473) and neuronal nitric oxide synthase phosphorylation. Similarly, caffeine was able to improve insulin sensitivity and decrease insulin levels in the NTS evoked by fructose. Caffeine intake also reduced the production of superoxide and expression of receptor of advanced glycation end product in the NTS. These results suggest that caffeine may enhance insulin receptor substrate 1-phosphatidylinositol 3-kinase-Akt-neuronal nitric oxide synthase signaling to decrease blood pressure by abolishing superoxide production in the NTS. PMID:24366086

  18. The Protective Effect of Apocynin on Cyclosporine A-Induced Hypertension and Nephrotoxicity in Rats.

    PubMed

    Ciarcia, Roberto; Damiano, Sara; Florio, Alessia; Spagnuolo, Manuela; Zacchia, Enza; Squillacioti, Caterina; Mirabella, Nicola; Florio, Salvatore; Pagnini, Ugo; Garofano, Tiziana; Polito, Maria Sole; Capasso, Giovambattista; Giordano, Antonio

    2015-09-01

    Cyclosporine A (CsA) is the prototype of immunosuppressant drugs that has provided new perspectives in human and veterinary medicine to prevent organ transplant rejection and to treat certain autoimmune diseases and dermatologic diseases. Unfortunately, the treatment with CSA is often limited by severe adverse effects such as hypertension and nephrotoxicity. Some data suggest that reactive oxygen species (ROS) and the oxidative stress play an important role in its pathogenesis, in particular the superoxide (O2 (-) ) that is the most powerful free radical generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase present mainly in the kidney. The present study has been designed to investigate the role of Apocynin a selective inhibitor of NADPH oxidase activity on cyclosporine-induced adverse effect. In this study, we have evaluated the effect of CsA, used alone or in association with Apocynin on blood pressure (BP), on glomerular filtration rate (GFR), on absoluted fluid reabsorption (Jv) in proximal tubule (PT), on O2 (-) concentration, and on nitric oxide (NO) production. We have demonstrated that CsA administration increases superoxide concentration in the aorta, decreases the NO concentration, reduces GFR and the Jv in PT, and induces a significant increase in BP. Moreover, we have shown that Apocynin treatment restores these hemodynamic alterations, as well as NO and superoxide productions. In conclusion, the reported data indicate that CsA induced nephrotoxicity and hypertension are related to NADPH oxidase activity, in fact Apocynin protects the kidney function and BP from toxic effects induced by CsA through the inhibition of NADPH oxidase activity. J. Cell. Biochem. 116: 1848-1856, 2015. © 2015 Wiley Periodicals, Inc. PMID:25704923

  19. Partners In Health and Brigham & Women's Hospitalist Program Background: Partners In Health (PIH) is a health and social justice organization with a

    E-print Network

    Derisi, Joseph

    Partners In Health and Brigham & Women's Hospitalist Program Background: Partners In Health (PIH) is a health and social justice organization with a mission to build high quality, comprehensive public health systems

  20. Angiotensin-II-induced reactive oxygen species along the SFO-PVN-RVLM pathway: implications in neurogenic hypertension.

    PubMed

    Braga, V A; Medeiros, I A; Ribeiro, T P; França-Silva, M S; Botelho-Ono, M S; Guimarăes, D D

    2011-09-01

    Neurogenic hypertension has been the subject of extensive research worldwide. This review is based on the premise that some forms of neurogenic hypertension are caused in part by the formation of angiotensin-II (Ang-II)-induced reactive oxygen species along the subfornical organ-paraventricular nucleus of the hypothalamus-rostral ventrolateral medulla pathway (SFO-PVN-RVLM pathway). We will discuss the recent contribution of our laboratory and others regarding the mechanisms by which neurons in the SFO (an important circumventricular organ) are activated by Ang-II, how the SFO communicates with two other important areas involved in sympathetic activity regulation (PVN and RVLM) and how Ang-II-induced reactive oxygen species participate along the SFO-PVN-RVLM pathway in the pathogenesis of neurogenic hypertension. PMID:21755262

  1. Hydrogen sulfide treatment reduces blood pressure and oxidative stress in angiotensin II-induced hypertensive mice.

    PubMed

    Al-Magableh, Mohammad R; Kemp-Harper, Barbara K; Hart, Joanne L

    2015-01-01

    Hydrogen sulfide (H2S) is increasingly recognized as a gasotransmitter with protective effects in the cardiovascular system. The aim of the study was to examine the effects of chronic NaHS treatment on blood pressure, vascular function and oxidative stress in an in vivo model of hypertension and oxidative stress. Male C57Bl6/J mice were rendered hypertensive with 0.7 mg kg(-1) per day angiotensin II (AngII) for 14 days administered via implanted mini-pumps. The mice were treated with NaHS (10 ?mol kg(-1) per day) to deliver H2S or an inhibitor of cystathionine-?-lyase, DL-propargylglycine (PPG 30 mg kg(-1) per day) via intraperitoneal (i.p.) injection. Systolic blood pressure was measured and vascular function examined by myography. Vascular superoxide production was measured by lucigenin-enhanced chemiluminescence. AngII infusion significantly increased systolic blood pressure (P < 0.001). This increase was significantly attenuated by treatment with NaHS (P < 0.001). Both aortic endothelial function and NO bioavailability were significantly attenuated in the AngII group (P < 0.01) but this attenuation was reversed by NaHS treatment. Similarly, aortic superoxide anion production was significantly enhanced by AngII (P < 0.01), and this was reversed by NaHS treatment, and also exacerbated by PPG treatment (P < 0.001). These data show that in a mouse model of hypertension and oxidative stress induced by AngII, exogenous H2S treatment in vivo reduces blood pressure, endothelial dysfunction and vascular oxidative stress, while inhibiting endogenous H2S production in vivo is deleterious. This furthers the evidence that H2S is a vasoprotective molecule that may be a useful treatment target in cardiovascular disease. PMID:25099489

  2. Agmatine induced NO dependent rat mesenteric artery relaxation and its impairment in salt-sensitive hypertension.

    PubMed

    Gadkari, Tushar V; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M; Joshi, Mahesh S

    2013-11-30

    l-Arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. l-Arginine initiated relaxations (EC50, 5.8±0.7mM; n=9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3±1.3mM; n=5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7±12.1?M; n=22), which was compromised by l-NAME (l-N(G)-nitroarginine methyl ester, an eNOS inhibitor), RX821002 (?-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9±23.4?M; n=5). The ?-2A AR, ?-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of ?-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension. PMID:23994446

  3. Agmatine Induced NO Dependent Rat Mesenteric Artery Relaxation and its Impairment in Salt-Sensitive Hypertension

    PubMed Central

    Gadkari, Tushar V.; Cortes, Natalie; Madrasi, Kumpal; Tsoukias, Nikolaos M.; Joshi, Mahesh S.

    2013-01-01

    L-arginine and its decarboxylated product, agmatine are important mediators of NO production and vascular relaxation. However, the underlying mechanisms of their action are not understood. We have investigated the role of arginine and agmatine in resistance vessel relaxation of Sprague-Dawley (SD) and Dahl salt-sensitive hypertensive rats. Second or 3rd-order mesenteric arterioles were cannulated in an organ chamber, pressurized and equilibrated before perfusing intraluminally with agonists. The vessel diameters were measured after mounting on the stage of a microscope fitted with a video camera. The gene expression in Dahl rat vessel homogenates was ascertained by real-time PCR. L-arginine initiated relaxations (EC50, 5.8 ± 0.7 mM; n = 9) were inhibited by arginine decarboxylase (ADC) inhibitor, difluoromethylarginine (DFMA) (EC50, 18.3 ± 1.3 mM; n = 5) suggesting that arginine-induced vessel relaxation was mediated by agmatine formation. Agmatine relaxed the SD rat vessels at significantly lower concentrations (EC50, 138.7 ± 12.1 ?M; n = 22), which was compromised by L-NAME (L-NG-Nitroarginine methyl ester, an eNOS inhibitor), RX821002 (?-2 AR antagonist) and pertussis toxin (G-protein inhibitor). The agmatine-mediated vessel relaxation from high salt Dahl rats was abolished as compared to that from normal salt rats (EC50, 143.9 ± 23.4 ?M; n = 5). The ?-2A AR, ?-2B AR and eNOS mRNA expression was downregulated in mesenteric arterioles of high-salt treated Dahl hypertensive rats. These findings demonstrate that agmatine facilitated the relaxation via activation of ?-2 adrenergic G-protein coupled receptor and NO synthesis, and this pathway is compromised in salt-sensitive hypertension. PMID:23994446

  4. CYP450 4A Inhibition Attenuates O2 Induced Arteriolar Constriction in Chronic but not Acute Goldblatt Hypertension

    PubMed Central

    Kunert, Mary Pat; Friesma, Jill; Falck, John R.; Lombard, Julian H.

    2009-01-01

    We explored the role of 20-hydroxy-5Z, 8Z, 11Z, 14Z-eicosatetraenoic acid (20-HETE) in oxygen-induced vasoconstriction in a normal renin form of hypertension [the 1 kidney-1 clip Goldblatt hypertensive rat (1K1C)] and a high renin form of hypertension [the 2 kidney-1 clip Goldblatt hypertensive rat (2K1C)]. A silver clip was placed around the left renal artery of adult Sprague-Dawley males. The right kidney was removed in the 1K1C group and left intact in the 2K1C group. Arteriolar responses to elevation of O2 concentration in the superfusion solution from 0% O2 to 21% O2 were determined in the in situ cremaster muscle before and after inhibition of cytochrome P450 4A ?-hydroxylase (CYP450 4A) with N-methyl-sulfonyl-12, 12-dibromododec-11-enamide (DDMS). Arteriolar constriction to elevated PO2 was enhanced in the chronic 1K1C but not the acute 1K1C or 2K1C. DDMS eliminated O2-induced arteriolar constriction in the 9 week 1K1C, but had no effect in the 2 wk 1K1C, and only partially inhibited O2-induced constriction of arterioles in the 4 wk 2K1C rat. These findings indicate that although the CYP4A/20-HETE system contributes to arteriolar constriction in response to elevated PO2 in the established stage of 1K1C renovascular hypertension, physiological alterations in other mechanisms are the primary determinants of O2-induced constriction of arterioles in the early and developing stages of 1K1C and 2K1C hypertension. PMID:19761780

  5. Inactivation of p53 Is Sufficient to Induce Development of Pulmonary Hypertension in Rats

    PubMed Central

    Jacquin, S.; Rincheval, V.; Mignotte, B.; Richard, S.; Humbert, M.; Mercier, O.; Londońo-Vallejo, A.; Fadel, E.; Eddahibi, S.

    2015-01-01

    Objective Pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterial hypertension (PAH) show similarities to cancer cells. Due to the growth-suppressive and pro-apoptotic effects of p53 and its inactivation in cancer, we hypothesized that the p53 pathway could be altered in PAH. We therefore explored the involvement of p53 in the monocrotaline (MCT) rat model of pulmonary hypertension (PH) and the pathophysiological consequences of p53 inactivation in response to animal treatment with pifithrin-? (PFT, an inhibitor of p53 activity). Methods and Results PH development was assessed by pulmonary arterial pressure, right ventricular hypertrophy and arterial wall thickness. The effect of MCT and PFT on lung p53 pathway expression was evaluated by western blot. Fourteen days of daily PFT treatment (2.2 mg/kg/day), similar to a single injection of MCT (60 mg/kg), induced PH and aggravated MCT-induced PH. In the first week after MCT administration and prior to PH development, p53, p21 and MDM2 protein levels were significantly reduced; whereas PFT administration effectively altered the protein level of p53 targets. Anti-apoptotic and pro-proliferative effects of PFT were revealed by TUNEL and MTT assays on cultured human PA-SMCs treated with 50 ?M PFT. Conclusions Pharmacological inactivation of p53 is sufficient to induce PH with a chronic treatment by PFT, an effect related to its anti-apoptotic and pro-proliferative properties. The p53 pathway was down-regulated during the first week in the rat MCT model. These in vivo experiments implicate the p53 pathway at the initiation stages of PH pathogenesis. PMID:26121334

  6. Vasopressin V1a receptor antagonism does not reverse adrenocorticotrophin-induced hypertension in the rat.

    PubMed

    Fraser, T B; Turner, S W; Wen, C; Li, M; Burrell, L M; Whitworth, J A

    2000-11-01

    1. The role of arginine vasopressin (AVP) was examined in adrenocorticotrophin (ACTH)-induced hypertension in Sprague-Dawley rats using the non-peptide AVP V1a receptor antagonist OPC 21268. 2. In an acute study, six rats were pretreated with ACTH for 11 days and direct arterial blood pressure (4 h), plasma osmolality and electrolyte concentrations were measured after OPC 21268 gavage. In a chronic study, 40 rats were randomly divided into four groups: (i) sham injection + sham gavage; (ii) ACTH + sham gavage; (iii) sham injection + OPC 21268; or (iv) ACTH + OPC-21268 for 16 days. Systolic blood pressure (SBP), water intake, urine volume (UV), urine osmolality and electrolytes, food intake, bodyweight and plasma osmolality and electrolyte concentrations were measured. 3. In the acute study, direct mean arterial blood pressure did not change with OPC 21268 (122+/-2 and 120+/-3 mmHg at 0 and 240 min, respectively). 4. In the chronic study, OPC 21268 did not affect ACTH-induced rises in blood pressure (from 125+/-2 (control) to 145+/-5 mmHg (group 4) compared with 122+/-3 (control) to 149+/-5 mmHg (group2)). Water intake and UV increased (from 29+/-2 to 83+/-6 mL/day; and from 5+/-1 to 36+/-5 mL/day, respectively) and the change in bodyweight decreased from 0+/-2 to -107+/-7 g. 5. These results suggest that AVP (at the V1a receptor) does not play a significant role in the maintenance of ACTH-induced hypertension. PMID:11071300

  7. Hydrogen sulfide is involved in dexamethasone-induced hypertension in rat.

    PubMed

    d'Emmanuele di Villa Bianca, Roberta; Mitidieri, Emma; Donnarumma, Erminia; Tramontano, Teresa; Brancaleone, Vincenzo; Cirino, Giuseppe; Bucci, Mariarosaria; Sorrentino, Raffaella

    2015-04-30

    Glucocorticoid (GC)-induced hypertension is a common clinical problem still poorly understood. The presence of GC receptor (GR) in vascular smooth muscle and endothelial cells suggests a direct role for GC in vasculature. In response to hemodynamic shear stress, endothelium tonically releases nitric oxide (NO), endothelial-derived hyperpolarizing factor (EDHF) and prostacyclin contributing to vascular homeostasis. Recently, hydrogen sulfide (H2S) has been proposed as a candidate for EDHF. H2S is endogenously mainly formed from L-cysteine by the action of cystathionine-?-synthase (CBS) and cystathionine-?-lyase (CSE). It plays many physiological roles and contributes to cardiovascular function. Here we have evaluated the role played by H2S in mesenteric arterial bed and in carotid artery harvested from rats treated with vehicle or dexamethasone (DEX; 1.5 mg/kg/day) for 8 days. During treatments systolic blood pressure was significantly increased in conscious rats. EDHF contribution was evaluated in ex-vivo by performing a concentration-response curve induced by acetylcholine (Ach) in presence of a combination of indomethacin and L-NG-Nitroarginine methyl ester in both vascular districts. EDHF-mediated relaxation was significantly reduced in DEX-treated group in both mesenteric bed and carotid artery. EDHF-mediated relaxation was abolished by pre-treatment with both apamin and charybdotoxin, inhibitors of small and big calcium-dependent potassium channels respectively, or with propargylglycine, inhibitor of CSE. Western blot analysis revealed a marked reduction in CBS and CSE expression as well as H2S production in homogenates of mesenteric arterial bed and carotid artery from DEX-treated rats. In parallel, H2S plasma levels were significantly reduced in DEX group compared with vehicle. In conclusion, an impairment in EDHF/H2S signaling occurs in earlier state of GC-induced hypertension in rats suggesting that counteracting this dysfunction may be beneficial to manage DEX-associated increase in blood pressure. PMID:25461303

  8. Selective endothelin-A receptor blockade attenuates endotoxin-induced pulmonary hypertension and pulmonary vascular dysfunction.

    PubMed

    Toney, Brent M; Fisher, Amanda J; Albrecht, Marjorie; Lockett, Angelia D; Presson, Robert G; Petrache, Irina; Lahm, Tim

    2014-06-01

    Endothelin-1 is a potent mediator of sepsis-induced pulmonary hypertension (PH). The pulmonary vascular effects of selective blockade of endothelin receptor subtype A (ETAR) during endotoxemia remain unknown. We hypothesized that selective ETAR antagonism attenuates endotoxin-induced PH and improves pulmonary artery (PA) vasoreactivity. Adult male Sprague-Dawley rats (250-450 g) received lipopolysaccharide (LPS; Salmonella typhimurium; 20 mg/kg intraperitoneally) or vehicle 6 hours before hemodynamic assessment and tissue harvest. The selective ETAR antagonist sitaxsentan (10 or 20 mg/kg) or vehicle was injected intravenously 3 hours after receipt of LPS. Right ventricular systolic pressure, mean arterial pressure (MAP), cardiac output (CO), oxygenation (P/F ratio), and serum bicarbonate were measured. Bronchoalveolar lavage (BAL) cell differential and lung wet-to-dry ratios were obtained. Endothelium-dependent and endothelium-independent vasorelaxations were determined in isolated PA rings. PA interleukin (IL)-1?, IL-6, tumor necrosis factor ? (TNF-?), and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) were measured. LPS caused PH, decreased MAP, CO, and serum bicarbonate, and increased PA IL-1?, IL-6, TNF-?, and iNOS mRNA. Sitaxsentan attenuated sepsis-induced PH and increased MAP. The P/F ratio, CO, serum bicarbonate, and BAL neutrophilia were not affected by sitaxsentan. In isolated PA rings, while not affecting phenylephrine-induced vasocontraction or endothelium-dependent relaxation, sitaxsentan dose-dependently attenuated LPS-induced alterations in endothelium-independent relaxation. PA cytokine mRNA levels were not significantly attenuated by ETAR blockade. We conclude that ETAR blockade attenuates endotoxin-induced alterations in systemic and PA pressures without negatively affecting oxygenation. This protective effect appears to be mediated not by attenuation of sepsis-induced cardiac dysfunction, acidosis, or alveolar inflammation but rather by improved endothelium-independent vasorelaxation. PMID:25006449

  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. Rats with Hypertension Induced by in utero Exposure to Maternal Low-Protein Diets Fail to Increase Blood Pressure in Response to a High Salt Intake

    Microsoft Academic Search

    Simon C. Langley-Evans; Alan A. Jackson

    1996-01-01

    Hypertension in the rat has been demonstrated to be determined in utero by exposure to maternal low-protein diets. Assessment was made of the response of rats with maternal diet-induced hypertension to a chronic high intake of sodium chloride. Normotensive and hypertensive animals were provided with either drinking water (control) or 1.5% sodium chloride over a 7-day period. Normotensive rats significantly

  11. Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

    NASA Technical Reports Server (NTRS)

    Pamnani, M. B.; Chen, S.; Haddy, F. J.; Yuan, C.; Mo, Z.

    1998-01-01

    We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

  12. The Complex Regulation of Tanshinone IIA in Rats with Hypertension-Induced Left Ventricular Hypertrophy

    PubMed Central

    Pang, Hui; Han, Bing; Yu, Tao; Peng, Zhen

    2014-01-01

    Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH), the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hypertensive rats (n?=?32) were randomized to receive tanshinone IIA (5, 10, 15 mg/kg per day) or 5% glucose injection (GS). Sham-operated rats (n?=?8) received 5%GS as control. Cardiac function and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson’s trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2) and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2) protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS) group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM) deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-?/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM deposition, and limiting apoptosis of cardiomyocytes and oxidative damage. PMID:24647357

  13. Attenuation of salt-induced hypertension by aqueous calyx extract of Hibiscus sabdariffa.

    PubMed

    Mojiminiyi, F B O; Audu, Z; Etuk, E U; Ajagbonna, O P

    2012-01-01

    The aqueous calyx extract of Hibiscus sabdariffa (HS) has a folk reputation as an antihypertensive agent. On account of its antioxidant properties and probably high K+ concentration, we hypothesized that HS may attenuate the development of salt-induced hypertension. Sprague-Dawley rats (n=8 each) were treated for 12 weeks as follows: control (normal diet + water), salt-loaded (8% salt diet + water), HS (normal diet + 6 mg/ml HS), salt+HS (8% salt diet + 6 mg/ml HS) and furosemide (normal diet+ 0.25mg/Kg furosemide). Their blood pressure and heart rates were measured and responses to noradrenalin and acetylcholine (0.01 mg/kg respectively) were estimated. The cationic concentration of 6 mg/ml HS was determined. The Na+ and K+ concentrations of 6 mg/ml HS were 3.6 and 840 mmol/l respectively. The mean arterial pressure (MAP±SEM; mmHg) of salt loaded rats (184.6±29.8) was significantly higher than control (113.2±3.0; P<0.05), HS (90.0±7.4; P<0.001) salt+HS (119.4±8.9; P<0.05) and furosemide (94.9±11.5; P<0.01). The MAP of salt+HS and control rats did not differ significantly and the effect of HS was comparable to furosemide. The pressor response to noradrenalin or vasodilator response to acetylcholine remained similar in all groups. These results suggest that HS attenuated the development of salt-induced hypertension and this attenuation may be associated with its high K+ content or high potassium: sodium ratio and not with altered pressor/depressor response to noradrenalin or acetylcholine. Also the effects of HS and furosemide on blood pressure are comparable. PMID:23652235

  14. Ghrelin counteracts salt-induced hypertension via promoting diuresis and renal nitric oxide production in Dahl rats.

    PubMed

    Aoki, Hirotaka; Nakata, Masanori; Dezaki, Katsuya; Lu, Ming; Gantulga, Darambazar; Yamamoto, Keiji; Shimada, Kazuyuki; Kario, Kazuomi; Yada, Toshihiko

    2013-01-01

    Ghrelin is the endogenous ligand for the growth hormone-secretagogue receptor expressed in various tissues including the heart, blood vessels and kidney. This study sought to determine the effects of long-term treatment with ghrelin (10 nmol/kg, twice a day, intraperitoneally) on the hypertension induced by high salt (8.0% NaCl) diet in Dahl salt-sensitive hypertensive (DS) rats. Systolic blood pressure (SBP) was measured by a tail cuff method. During the treatment period for 3 weeks, high salt diet increased blood pressure compared to normal salt (0.3% NaCl) diet, and this hypertension was partly but significantly (P<0.01) attenuated by simultaneous treatment with ghrelin. Ghrelin significantly increased urine volume and tended to increase urine Na? excretion. Furthermore, ghrelin increased urine nitric oxide (NO) excretion and tended to increase renal neuronal nitric oxide synthase (nNOS) mRNA expression. Ghrelin did not alter the plasma angiotensin II level and renin activity, nor urine catecholamine levels. Furthermore, ghrelin prevented the high salt-induced increases in heart thickness and plasma ANP mRNA expression. These results demonstrate that long-term ghrelin treatment counteracts salt-induced hypertension in DS rats primarily through diuretic action associated with increased renal NO production, thereby exerting cardio-protective effects. PMID:23328675

  15. Time-dependent phenotypic and contractile changes of pulmonary artery in chronic hypoxia-induced pulmonary hypertension.

    PubMed

    Aoshima, Daigo; Murata, Takahisa; Hori, Masatoshi; Ozaki, Hiroshi

    2009-06-01

    Phenotypic and contractile changes in pulmonary arterial smooth muscle cells (PASMCs) were examined in rats with pulmonary hypertension induced by hypoxia. Exposure to hypoxia induced pulmonary hypertension within 1-4 weeks. Staining with BrdU revealed that proliferative activities of PASMCs peaked at 1 week of hypoxic exposure, and then moderate proliferative activity was maintained for the next 2-4 weeks. The beta-actin/alpha-actin ratio also increased at 1-2 weeks of exposure to hypoxia. Absolute contractility of the pulmonary arterial ring continuously decreased during hypoxia, whereas the basal active tonus of the pulmonary artery increased at 1-3 weeks. Nicardipine, the ETA-receptor antagonis, CI-1034 and the rho-kinase inhibitor Y27632 partially inhibited the elevated active tonus. Endothelin-1 content in the pulmonary hypertensive lung was continuously increased during exposure to hypoxia. In conclusion, the hypoxia-induced proliferative activity of PASMCs comprised a transient phase followed by a sustained phase. The change in PASMCs from a contractile to a synthetic phenotype also correlated with proliferative activity, which subsequently decreased PASMC contractility. The continuous production of endothelin-1 upon hypoxic exposure might contribute to the increased basal tonus of the pulmonary arterial wall, which might subsequently increase pulmonic arterial pressure, resulting in accelerated pulmonary hypertension. PMID:19498269

  16. Inhibition of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension

    PubMed Central

    Hameed, Abdul G.; Arnold, Nadine D.; Chamberlain, Janet; Pickworth, Josephine A.; Paiva, Claudia; Dawson, Sarah; Cross, Simon; Long, Lu; Zhao, Lan; Morrell, Nicholas W.; Crossman, David C.; Newman, Christopher M.H.; Kiely, David G.; Francis, Sheila E.

    2012-01-01

    Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by the progressive narrowing and occlusion of small pulmonary arteries. Current therapies fail to fully reverse this vascular remodeling. Identifying key pathways in disease pathogenesis is therefore required for the development of new-targeted therapeutics. We have previously reported tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) immunoreactivity within pulmonary vascular lesions from patients with idiopathic PAH and animal models. Because TRAIL can induce both endothelial cell apoptosis and smooth muscle cell proliferation in the systemic circulation, we hypothesized that TRAIL is an important mediator in the pathogenesis of PAH. We demonstrate for the first time that TRAIL is a potent stimulus for pulmonary vascular remodeling in human cells and rodent models. Furthermore, antibody blockade or genetic deletion of TRAIL prevents the development of PAH in three independent rodent models. Finally, anti-TRAIL antibody treatment of rodents with established PAH reverses pulmonary vascular remodeling by reducing proliferation and inducing apoptosis, improves hemodynamic indices, and significantly increases survival. These preclinical investigations are the first to demonstrate the importance of TRAIL in PAH pathogenesis and highlight its potential as a novel therapeutic target to direct future translational therapies. PMID:23071256

  17. Inhibition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension.

    PubMed

    Hameed, Abdul G; Arnold, Nadine D; Chamberlain, Janet; Pickworth, Josephine A; Paiva, Claudia; Dawson, Sarah; Cross, Simon; Long, Lu; Zhao, Lan; Morrell, Nicholas W; Crossman, David C; Newman, Christopher M H; Kiely, David G; Francis, Sheila E; Lawrie, Allan

    2012-10-22

    Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by the progressive narrowing and occlusion of small pulmonary arteries. Current therapies fail to fully reverse this vascular remodeling. Identifying key pathways in disease pathogenesis is therefore required for the development of new-targeted therapeutics. We have previously reported tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) immunoreactivity within pulmonary vascular lesions from patients with idiopathic PAH and animal models. Because TRAIL can induce both endothelial cell apoptosis and smooth muscle cell proliferation in the systemic circulation, we hypothesized that TRAIL is an important mediator in the pathogenesis of PAH. We demonstrate for the first time that TRAIL is a potent stimulus for pulmonary vascular remodeling in human cells and rodent models. Furthermore, antibody blockade or genetic deletion of TRAIL prevents the development of PAH in three independent rodent models. Finally, anti-TRAIL antibody treatment of rodents with established PAH reverses pulmonary vascular remodeling by reducing proliferation and inducing apoptosis, improves hemodynamic indices, and significantly increases survival. These preclinical investigations are the first to demonstrate the importance of TRAIL in PAH pathogenesis and highlight its potential as a novel therapeutic target to direct future translational therapies. PMID:23071256

  18. Structural and functional prevention of hypoxia-induced pulmonary hypertension by individualized exercise training in mice.

    PubMed

    Weissmann, Norbert; Peters, Dorothea M; Klöpping, Christina; Krüger, Karsten; Pilat, Christian; Katta, Susmitha; Seimetz, Michael; Ghofrani, Hossein A; Schermuly, Ralph T; Witzenrath, Martin; Seeger, Werner; Grimminger, Friedrich; Mooren, Frank C

    2014-06-01

    Pulmonary hypertension (PH) is a disease with a poor prognosis characterized by a vascular remodeling process and an increase in pulmonary vascular resistance. While a variety of reports demonstrated that exercise training exerts beneficial effects on exercise performance and quality of life in PH patients, it is not known how physical exercise affects vascular remodeling processes occurring in hypoxia-induced PH. Therefore, we investigated the effect of individualized exercise training on the development of hypoxia-induced PH in mice. Training effects were compared with pharmacological treatment with the phosphodiesterase 5 inhibitor Sildenafil or a combination of training plus Sildenafil. Trained mice who received Sildenafil showed a significantly improved walking distance (from 88.9 ± 8.1 to 146.4 ± 13.1 m) and maximum oxygen consumption (from 93.3 ± 2.9 to 105.5 ± 2.2% in combination with Sildenafil, to 102.2 ± 3.0% with placebo) compared with sedentary controls. Right ventricular systolic pressure, measured by telemetry, was at the level of healthy normoxic animals, whereas right heart hypertrophy did not benefit from training. Most interestingly, the increase in small pulmonary vessel muscularization was prevented by training. Respective counterregulatory processes were detected for the nitric oxide-soluble guanylate cyclase-phosphodiesterase system. We conclude that individualized daily exercise can prevent vascular remodeling in hypoxia-induced PH. PMID:24705723

  19. Thymosin Beta 4 Protects Mice from Monocrotaline-Induced Pulmonary Hypertension and Right Ventricular Hypertrophy

    PubMed Central

    Wu, Liling; Gupta, Sudhiranjan

    2014-01-01

    Pulmonary hypertension (PH) is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH) and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC) proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (T?4) is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether T?4 has any protective role in PH. The purpose of this study is to evaluate the whether T?4 can be used as a vascular-protective agent. In monocrotaline (MCT)-induced PH mouse model, we showed that mice treated with T?4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that T?4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for T?4 and may consider as vasculo-protective agent for the treatment of PH induced RVH. PMID:25412097

  20. Cerium oxide nanoparticles attenuate monocrotaline induced right ventricular hypertrophy following pulmonary arterial hypertension.

    PubMed

    Kolli, Madhukar B; Manne, Nandini D P K; Para, Radhakrishna; Nalabotu, Siva K; Nandyala, Geeta; Shokuhfar, Tolou; He, Kun; Hamlekhan, Azhang; Ma, Jane Y; Wehner, Paulette S; Dornon, Lucy; Arvapalli, Ravikumar; Rice, Kevin M; Blough, Eric R

    2014-12-01

    Cerium oxide (CeO2) nanoparticles have been posited to exhibit potent anti-oxidant activity which may allow for the use of these materials in biomedical applications. Herein, we investigate whether CeO2 nanoparticle administration can diminish right ventricular (RV) hypertrophy following four weeks of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were randomly divided into three groups: control, MCT only (60 mg/kg), or MCT + CeO2 nanoparticle treatment (60 mg/kg; 0.1 mg/kg). Compared to the control group, the RV weight to body weight ratio was 45% and 22% higher in the MCT and MCT + CeO2 groups, respectively (p < 0.05). Doppler echocardiography demonstrated that CeO2 nanoparticle treatment attenuated monocrotaline-induced changes in pulmonary flow and RV wall thickness. Paralleling these changes in cardiac function, CeO2 nanoparticle treatment also diminished MCT-induced increases in right ventricular (RV) cardiomyocyte cross sectional area, ?-myosin heavy chain, fibronectin expression, protein nitrosylation, protein carbonylation and cardiac superoxide levels. These changes with treatment were accompanied by a decrease in the ratio of Bax/Bcl2, diminished caspase-3 activation and reduction in serum inflammatory markers. Taken together, these data suggest that CeO2 nanoparticle administration may attenuate the hypertrophic response of the heart following PAH. PMID:25224369

  1. Thymosin Beta 4 protects mice from monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy.

    PubMed

    Wei, Chuanyu; Kim, Il-Kwon; Li, Li; Wu, Liling; Gupta, Sudhiranjan

    2014-01-01

    Pulmonary hypertension (PH) is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH) and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC) proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (T?4) is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether T?4 has any protective role in PH. The purpose of this study is to evaluate the whether T?4 can be used as a vascular-protective agent. In monocrotaline (MCT)-induced PH mouse model, we showed that mice treated with T?4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that T?4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for T?4 and may consider as vasculo-protective agent for the treatment of PH induced RVH. PMID:25412097

  2. 2-Methoxyestradiol Attenuates Bleomycin-Induced Pulmonary Hypertension and Fibrosis in Estrogen-Deficient Rats

    PubMed Central

    Tofovic, Stevan P.; Zhang, Xinchen; Jackson, Edwin K.; Zhu, Hong; Petrusevska, Gordana

    2009-01-01

    Pulmonary hypertension (PH) is a common and life-threatening complication of pulmonary fibrosis. Estradiol (E2) is protective in experimental PH, and its non-estrogenic metabolite 2-methoxyestradiol (2ME) prevents the development and retards the progression of monocrotaline-induced PH in male and female rats. However, the effects of E2 and 2ME on pulmonary fibrosis and associated PH have not been examined. Therefore, we compared the growth-inhibitory effects of E2 and 2ME in human lung fibroblasts (hLFs) and pulmonary vascular smooth muscle cells (hPASMCs), and we investigated the effects of estrogen deficiency and 2ME on bleomycin-induced pulmonary fibrosis and PH. Intact and ovariectomized (OVX) female Sprague Dawley rats were administered intratracheally either saline or bleomycin (15 IU/kg), and a subset of OVX bleomycin-treated rats received 2ME (10 ?g/kg/h) for 21 days. Estradiol had only limited inhibitory effects on growth in hPASMCs and no effect in hLFs, whereas 2ME exhibited strong and concentration-dependent (1?10 ?M) antimitogenic effects in both cell types. Bleomycin caused lung injury/PH (significantly increased lung and right ventricle (RV) weights, RV peak systolic pressure (RVPSP), and RV/left ventricle+septum ratio (RV/LV+S); caused medial hypertrophy and adventitial widening of pulmonary arteries; induced marked focal/diffuse fibrosis with diffuse infiltration of inflammatory (ED1+) cells; and resulted in 30% mortality). OVX exacerbated the disease and increased mortality (to 75%); whereas 2ME tended to reduce mortality (55.5%) and in surviving animals reduced RVPSP and RV/LV+S ratio, and attenuated vascular remodeling, pulmonary inflammation and fibrosis. This study suggests that 2ME may have protective effects in bleomycin-induced PH and fibrosis. Further investigation of 2ME in pulmonary fibrosis and PH is warranted. PMID:19540933

  3. Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection.

    PubMed

    Zhu, Rong; Bi, Li-Qing; Wu, Su-Ling; Li, Lan; Kong, Hui; Xie, Wei-Ping; Wang, Hong; Meng, Zi-Li

    2015-08-01

    The present study aimed to investigate the protective effects of iptakalim, an adenosine triphosphate (ATP)-sensitive potassium channel opener, on the inflammation of the pulmonary artery and endothelial cell injury in a hypoxia?induced pulmonary arterial hypertension (PAH) rat model. Ninety?six Sprague?Dawley rats were placed into normobaric hypoxia chambers for four weeks and were treated with iptakalim (1.5 mg/kg/day) or saline for 28 days. The right ventricle systolic pressures (RVSP) were measured and small pulmonary arterial morphological alterations were analyzed with hematoxylin and eosin staining. Enzyme?linked immunosorbent assay (ELISA) was performed to analyze the content of interleukin (IL)?1? and IL?10. Immunohistochemical analysis for ED1+ monocytes was performed to detect the inflammatory cells surrounding the pulmonary arterioles. Western blot analysis was performed to analyze the expression levels of platelet endothelial cell adhesion molecule?1 (PECAM?1) and endothelial nitric oxide synthase (eNOS) in the lung tissue. Alterations in small pulmonary arteriole morphology and the ultrastructure of pulmonary arterial endothelial cells were observed via light and transmission electron microscopy, respectively. Iptakalim significantly attenuated the increase in mean pulmonary artery pressure, RVSP, right ventricle to left ventricle plus septum ratio and small pulmonary artery wall remodeling in hypoxia?induced PAH rats. Iptakalim also prevented an increase in IL?1? and a decrease in IL?10 in the peripheral blood and lung tissue, and alleviated inflammatory cell infiltration in hypoxia?induced PAH rats. Furthermore, iptakalim enhanced PECAM?1 and eNOS expression and prevented the endothelial cell injury induced by hypoxic stimuli. Iptakalim suppressed the pulmonary arteriole and systemic inflammatory responses and protected against the endothelial damage associated with the upregulation of PECAM?1 and eNOS, suggesting that iptakalim may represent a potential therapeutic agent for PAH. PMID:25936382

  4. Attenuation of the extract from Moringa oleifera on monocrotaline-induced pulmonary hypertension in rats.

    PubMed

    Chen, Kang-Hu; Chen, Yi-Jui; Yang, Chao-Hsun; Liu, Kuo-Wei; Chang, Junn-Liang; Pan, Shwu-Fen; Lin, Tzer-Bin; Chen, Mei-Jung

    2012-02-29

    The purpose of this study was to determine the effects of an extract from Moringa oleifera (MO) on the development of monocrotaline (MCT)-induced pulmonary hypertension (PH) in Wistar rats. An ethanol extraction was performed on dried MO leaves, and HPLC analysis identified niaziridin and niazirin in the extract. PH was induced with a single subcutaneous injection of MCT (60 mg/kg) which resulted in increases in pulmonary arterial blood pressure (Ppa) and in thickening of the pulmonary arterial medial layer in the rats. Three weeks after induction, acute administration of the MO extract to the rats decreased Ppa in a dose-dependent manner that reached statistical significance at a dose of 4.5 mg of freeze-dried extract per kg body weight. The reduction in Ppa suggested that the extract directly relaxed the pulmonary arteries. To assay the effects of chronic administration of the MO extract on PH, control, MCT and MCT+MO groups were designated. Rats in the control group received a saline injection; the MCT and MCT+MO groups received MCT to induce PH. During the third week after MCT treatment, the MCT+MO group received daily i.p. injections of the MO extract (4.5 mg of freeze-dried extract/kg of body weight). Compared to the control group, the MCT group had higher Ppa and thicker medial layers in the pulmonary arteries. Chronic treatments with the MO extract reversed the MCT-induced changes. Additionally, the MCT group had a significant elevation in superoxide dismutase activity when normalized by the MO extract treatments. In conclusion, the MO extract successfully attenuated the development of PH via direct vasodilatation and a potential increase in antioxidant activity. PMID:22242951

  5. The anti-hypertensive drug reserpine induces neuronal cell death through inhibition of autophagic flux.

    PubMed

    Lee, Kang Il; Kim, Min Ju; Koh, Hyongjong; Lee, Jin I; Namkoong, Sim; Oh, Won Keun; Park, Junsoo

    2015-07-10

    Reserpine is a well-known medicine for the treatment of hypertension and schizophrenia, but its administration can induce Parkinson's disease (PD)-like symptoms in humans and animals. Reserpine inhibits the vesicular transporter of monoamines and depletes the brain of monoamines such as dopamine. However, the cellular function of reserpine is not fully understood. In this report, we present one possible mechanism by which reserpine may contribute to PD-like symptoms. Reserpine treatment induced the formation of enlarged autophagosomes by inhibiting the autophagic flux and led to accumulation of p62, an autophagy adapter molecule. In particular, reserpine treatment increased the level of ?-synuclein protein and led to accumulation of ?-synuclein in autophagosomes. Treatment with rapamycin enhanced the effect of reserpine by further increasing the level of ?-synuclein and neuronal cell death. Drosophila raised on media containing reserpine showed loss of dopaminergic neurons. Furthermore, cotreatment with reserpine and rapamycin aggravated the loss of dopaminergic neurons. Our results suggest that reserpine contributes to the loss of dopaminergic neurons by interfering with autophagic flux. PMID:25976674

  6. Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension.

    PubMed

    Spranger, Marty D; Kaur, Jasdeep; Sala-Mercado, Javier A; Machado, Tiago M; Krishnan, Abhinav C; Alvarez, Alberto; O'Leary, Donal S

    2015-04-01

    During dynamic exercise, muscle metaboreflex activation (MMA; induced via partial hindlimb ischemia) markedly increases mean arterial pressure (MAP), and MAP is sustained when the ischemia is maintained following the cessation of exercise (postexercise muscle ischemia, PEMI). We previously reported that the sustained pressor response during PEMI in normal individuals is driven by a sustained increase in cardiac output (CO) with no peripheral vasoconstriction. However, we have recently shown that the rise in CO with MMA is significantly blunted in hypertension (HTN). The mechanisms sustaining the pressor response during PEMI in HTN are unknown. In six chronically instrumented canines, hemodynamic responses were observed during rest, mild exercise (3.2 km/h), MMA, and PEMI in the same animals before and after the induction of HTN [Goldblatt two kidney, one clip (2K1C)]. In controls, MAP, CO and HR increased with MMA (+52 ± 6 mmHg, +2.1 ± 0.3 l/min, and +37 ± 7 beats per minute). After induction of HTN, MAP at rest increased from 97 ± 3 to 130 ± 4 mmHg, and the metaboreflex responses were markedly attenuated (+32 ± 5 mmHg, +0.6 ± 0.2 l/min, and +11 ± 3 bpm). During PEMI in HTN, HR and CO were not sustained, and MAP fell to normal recovery levels. We conclude that the attenuated metaboreflex-induced HR, CO, and MAP responses are not sustained during PEMI in HTN. PMID:25632024

  7. Hypoxia-induced mitogenic factor (FIZZ1/RELM?) induces endothelial cell apoptosis and subsequent interleukin-4-dependent pulmonary hypertension

    PubMed Central

    Takimoto, Eiki; Zhang, Ailan; Weiner, Noah C.; Meuchel, Lucas W.; Berger, Alan E.; Cheadle, Chris; Johns, Roger A.

    2014-01-01

    Pulmonary hypertension (PH) is characterized by elevated pulmonary artery pressure that leads to progressive right heart failure and ultimately death. Injury to endothelium and consequent wound repair cascades have been suggested to trigger pulmonary vascular remodeling, such as that observed during PH. The relationship between injury to endothelium and disease pathogenesis in this disorder remains poorly understood. We and others have shown that, in mice, hypoxia-induced mitogenic factor (HIMF, also known as FIZZ1 or RELM?) plays a critical role in the pathogenesis of lung inflammation and the development of PH. In this study, we dissected the mechanism by which HIMF and its human homolog resistin (hRETN) induce pulmonary endothelial cell (EC) apoptosis and subsequent lung inflammation-mediated PH, which exhibits many of the hallmarks of the human disease. Systemic administration of HIMF caused increases in EC apoptosis and interleukin (IL)-4-dependent vascular inflammatory marker expression in mouse lung during the early inflammation phase. In vitro, HIMF, hRETN, and IL-4 activated pulmonary microvascular ECs (PMVECs) by increasing angiopoietin-2 expression and induced PMVEC apoptosis. In addition, the conditioned medium from hRETN-treated ECs had elevated levels of endothelin-1 and caused significant increases in pulmonary vascular smooth muscle cell proliferation. Last, HIMF treatment caused development of PH that was characterized by pulmonary vascular remodeling and right heart failure in wild-type mice but not in IL-4 knockout mice. These data suggest that HIMF contributes to activation of vascular inflammation at least in part by inducing EC apoptosis in the lung. These events lead to subsequent PH. PMID:24793164

  8. Role of VPAC2 receptor in monocrotaline-induced pulmonary hypertension in rats.

    PubMed

    Koga, Motokazu; Mizuno, Yusuke; Watanabe, Itaru; Kawakami, Hiromasa; Goto, Takahisa

    2014-08-15

    Pulmonary hypertension (PH) is associated with significant morbidity and mortality. Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP) have pulmonary vasodilatory and positive inotropic effects via receptors VPAC1 and VPAC2, which possess a similar affinity for both peptides, and PAC1, a PACAP-preferring receptor. VIP is a promising option for PH treatment; however, various physiological effects of VIP have limited its clinical use. We investigated the effects of VPAC1 and VPAC2 selective agonists VIP and PACAP to explore more appropriate means of treatment for PH. We examined hemodynamic changes in right ventricular systolic pressure (RVSP), systemic blood pressure (SBP), total pulmonary resistance index (TPRI), total systemic resistance index, and cardiac index (CI) in response to their agonists with monocrotaline (MCT)-induced PH and explored involvement of VIP/PACAP expression and receptors in PH. Sprague-Dawley rats were divided into the MCT group (administered MCT 60 mg/kg) and control group. In MCT-induced PH, decreased VIP and PACAP were associated with upregulation of VPAC1, VPAC2, and PAC1 in lung tissues. Intravenous injection of VPAC2-selective agonist BAY 55-9837 and VIP, but not [Ala(11,22,28)]VIP, improved the CI. The decrease in SBP with VPAC2 agonist was significantly less than that in the control. Although they decreased SBP, these agonists hardly affected RVSP in the control. Activation of VPAC2 receptor with BAY 55-9837 effectively improved RVSP, TPRI, and CI in MCT-induced PH, suggesting a VPAC2 agonist as a possible promising treatment for PH. PMID:24947028

  9. Right ventricular cyclic nucleotide signaling is decreased in hyperoxia-induced pulmonary hypertension in neonatal mice.

    PubMed

    Heilman, Rachel P; Lagoski, Megan B; Lee, Keng Jin; Taylor, Joann M; Kim, Gina A; Berkelhamer, Sara K; Steinhorn, Robin H; Farrow, Kathryn N

    2015-06-15

    Pulmonary hypertension (PH) and right ventricular hypertrophy (RVH) affect 25-35% of premature infants with significant bronchopulmonary dysplasia (BPD), increasing morbidity and mortality. We sought to determine the role of phosphodiesterase 5 (PDE5) in the right ventricle (RV) and left ventricle (LV) in a hyperoxia-induced neonatal mouse model of PH and RVH. After birth, C57BL/6 mice were placed in room air (RA) or 75% O2 (CH) for 14 days to induce PH and RVH. Mice were euthanized at 14 days or recovered in RA for 14 days or 42 days prior to euthanasia at 28 or 56 days of age. Some pups received sildenafil or vehicle (3 mg·kg(-1)·dose(-1) sc) every other day from P0. RVH was assessed by Fulton's index [RV wt/(LV + septum) wt]. PDE5 protein expression was analyzed via Western blot, PDE5 activity was measured by commercially available assay, and cGMP was measured by enzyme-linked immunoassay. Hyperoxia induced RVH in mice after 14 days, and RVH did not resolve until 56 days of age. Hyperoxia increased PDE5 expression and activity in RV, but not LV + S, after 14 days. PDE5 expression normalized by 28 days of age, but PDE5 activity did not normalize until 56 days of age. Sildenafil given during hyperoxia prevented RVH, decreased RV PDE5 activity, and increased RV cGMP levels. Mice with cardiac-specific overexpression of PDE5 had increased RVH in RA. These findings suggest normal RV PDE5 function is disrupted by hyperoxia, and elevated PDE5 contributes to RVH and remodeling. Therefore, in addition to impacting the pulmonary vasculature, sildenafil also targets PDE5 in the neonatal mouse RV and decreases RVH. PMID:25862831

  10. Glycyrrhizin could reduce ocular hypertension induced by triamcinolone acetonide in rabbits

    PubMed Central

    Song, Zhengyu; Gong, Yuanyuan; Liu, Haiyun; Ren, Qiushi

    2011-01-01

    Purpose To evaluate the hypotensive effects of glycyrrhizin (GL) on a rabbit model of ocular hypertension (OH) induced by triamcinolone acetonide (TA). Methods Forty New Zealand White Rabbits were divided as follows: control (intravitreal injection of sterile saline solution); GL (intravitreal injection of sterile saline solution, then fed with 25mg GL/day); TA (intravitreal TA injection); TA+GL (intravitreal TA injection, then fed with GL) and GL+TA (pre-treated with GL for 3 days, then got TA injection and the following GL treatment). Intraocular pressure (IOP), flash electroretinogram (flash ERG) and flash visual evoked potential (flash VEP) were measured during the follow-up (28 days). The aqueous humor was analyzed, using 1H-nuclear magnetic resonance spectroscopy and principal components analysis (PCA). Results IOP elevation was observed in the TA group during the follow-up, compared to the controls (p<0.01). The IOP was decreased in the TA+GL group and the GL+TA group, compared to the TA group (p<0.05). Both in flash ERG and VEP, the amplitudes were decreased, and the implicit time was prolonged in the TA group, compared to the controls (p<0.05); and the parameters were improved after intervention of GL, compared to the TA group (p<0.05). PCA results indicated that TA could affect ocular metabolism (especially the sugar metabolism), and GL could inhibit it. Conclusions The administration of GL could suppress OH induced by TA in rabbits, and improve their electrophysiological parameters. Metabolomics is a useful tool in ophthalmology research. Our results indicate that TA-induced ocular metabolism changes could be compensated by GL. PMID:21850181

  11. Pyrrolidine dithiocarbamate restores endothelial cell membrane integrity and attenuates monocrotaline-induced pulmonary artery hypertension.

    PubMed

    Huang, Jing; Kaminski, Pawel M; Edwards, John G; Yeh, Albert; Wolin, Michael S; Frishman, William H; Gewitz, Michael H; Mathew, Rajamma

    2008-06-01

    Monocrotaline (MCT)-induced pulmonary artery hypertension (PAH) in rats is preceded by an inflammatory response, progressive endothelial cell membrane disruption, reduction in the expression of caveolin-1, and reciprocal activation of STAT3 (PY-STAT3). Superoxide and NF-kappaB have been implicated in PAH. To evaluate the role of caveolin-1, PY-STAT3 activation, and superoxide in PAH, MCT-injected rats were treated daily with pyrrolidine dithiocarbamate (PDTC; starting on days 1, 3, and 14 x 2 wk), an inhibitor of inflammation and NF-kappaB activation. Hemodynamic data, the expression of inhibitory (I)-kappaBalpha, caveolin-1, and Tie2 (a membrane protein), activation of PY-STAT3 and NF-kappaB, and superoxide chemiluminescence were examined. Rats developed progressive PAH at 2 wk post-MCT. There was progressive reduction in the expression of caveolin-1, Tie2, and activation of PY-STAT3 in the lungs. Reduction in I-kappaBalpha expression was present at 2 and 4 wk post-MCT. Superoxide chemiluminescence and NF-kappaB activation were observed only at 2 wk post-MCT and both decreased by 4 wk post-MCT despite progressive PAH. PDTC (starting on days 1 and 3) rescued caveolin-1 and Tie2, reversed MCT-induced PY-STAT3 activation, and attenuated PAH. In addition, PDTC restored I-kappaBalpha expression and reduced superoxide chemiluminescence at 2 wk but did not inhibit NF-kappaB activation despite attenuation of PAH. PDTC had no effect on established PAH. Increased superoxide chemiluminescence and NF-kappaB activation appear to be a transient phenomenon in the MCT model. Thus the disruption of endothelial cell membrane integrity resulting in caveolin-1 loss and reciprocal activation of PY-STAT3 plays a key role in the MCT-induced PAH. PMID:18390833

  12. Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats.

    PubMed

    Conde, Silvia V; Nunes da Silva, Tiago; Gonzalez, Constancio; Mota Carmo, Miguel; Monteiro, Emilia C; Guarino, Maria P

    2012-01-01

    We tested the hypothesis that long-term caffeine intake prevents the development of insulin resistance and hypertension in two pathological animal models: the high-fat (HF) and the high-sucrose (HSu) diet rat. We used six groups of animals: control; caffeine-treated (Caff; 1 g/l in drinking water during 15 d); HF; caffeine-treated HF (HFCaff); HSu; caffeine-treated HSu (HSuCaff). Insulin sensitivity was assessed using the insulin tolerance test. Blood pressure, weight gain, visceral fat, hepatic glutathione, plasma caffeine, insulin and NO, and serum NEFA and catecholamines were measured. Caffeine reversed insulin resistance and hypertension induced by both the HF and HSu diets. In the HF-fed animals caffeine treatment restored fasting insulin levels to control values and reversed increased weight gain and visceral fat mass. In the HSu group, caffeine reversed fasting hyperglycaemia and restored NEFA to control values. There were no changes either in plasma NO or in hepatic glutathione levels. In contrast, caffeine totally prevented the increase in serum catecholamines induced by HF and HSu diets. To test the hypothesis that inhibition of the sympathetic nervous system prevents the development of diet-induced insulin resistance we administered carvedilol, an antagonist of ?1, ?2 and also ?1 adrenoceptors, to HF and HSu rats. Carvedilol treatment fully prevented diet-induced insulin resistance and hypertension, mimicking the effect of caffeine. We concluded that long-term caffeine intake prevented the development of insulin resistance and hypertension in HF and HSu models and that this effect was related to a decrease in circulating catecholamines. PMID:21733336

  13. Altered regulation of renal nitric oxide and atrial natriuretic peptide systems in angiotensin II-induced hypertension

    Microsoft Academic Search

    Eun Hui Bae; Seong Kwon Ma; JongUn Lee; Soo Wan Kim

    2011-01-01

    The present study was aimed to determine whether there is an altered role of local nitric oxide (NO) and atrial natriuretic peptide (ANP) systems in the kidney in association with the angiotensin (Ang) II-induced hypertension. Male Sprague–Dawley rats were used. Ang II (100ng·min?1·kg?1) was infused through entire time course. Thirteenth day after beginning the regimen, kidneys were taken. The protein

  14. Alteration of Pulmonary Artery Integrin Levels in Chronic Hypoxia and Monocrotaline-Induced Pulmonary Hypertension

    Microsoft Academic Search

    Anita Umesh; Omkar Paudel; Yuan-Ning Cao; Allen C. Myers; James S. K. Sham

    2011-01-01

    Background: Pulmonary hypertension is associated with vascular remodeling and increased extracellular matrix (ECM) deposition. While the contribution of ECM in vascular remodeling is well documented, the roles played by their receptors, integrins, in pulmonary hypertension have received little attention. Here we characterized the changes of integrin expression in endothelium-denuded pulmonary arteries (PAs) and aorta of chronic hypoxia as well as

  15. Maintenance of GLUT4 expression in smooth muscle prevents hypertension-induced changes in vascular reactivity

    PubMed Central

    Atkins, Kevin B; Seki, Yoshinori; Saha, Jharna; Eichinger, Felix; Charron, Maureen J; Brosius, Frank C

    2015-01-01

    Previous studies have shown that expression of GLUT4 is decreased in arterial smooth muscle of hypertensive rats and mice and that total body overexpression of GLUT4 in mice prevents enhanced arterial reactivity in hypertension. To demonstrate that the effect of GLUT4 overexpression on vascular responses is dependent on vascular smooth muscle GLUT4 rather than on some systemic effect we developed and tested smooth-muscle-specific GLUT4 transgenic mice (SMG4). When made hypertensive with angiotensin II, both wild-type and SMG4 mice exhibited similarly increased systolic blood pressure. Responsiveness to phenylephrine, serotonin, and prostaglandin F2? was significantly increased in endothelium-intact aortic rings from hypertensive wild-type mice but not in aortae of SMG4 mice. Inhibition of Rho-kinase equally reduced serotonin-stimulated contractility in aortae of hypertensive wild-type and SMG4-mice. In addition, acetylcholine-stimulated relaxation was significantly decreased in aortic rings of hypertensive wild-type mice, but not in rings of SMG4 mice. Inhibition of either prostacylin receptors or cyclooxygenase-2 reduced relaxation in rings of hypertensive SMG4 mice. Inhibition of cyclooxygenase-2 had no effect on relaxation in rings of hypertensive wild-type mice. Cyclooxygenase-2 protein expression was decreased in hypertensive wild-type aortae but not in hypertensive SMG4 aortae compared to nonhypertensive controls. Our results demonstrate that smooth muscle expression of GLUT4 exerts a major effect on smooth muscle contractile responses and endothelium-dependent vasorelaxation and that normal expression of GLUT4 in vascular smooth muscle is required for appropriate smooth muscle and endothelial responses. PMID:25677552

  16. Gene therapy strategies in glaucoma and application for steroid-induced hypertension

    PubMed Central

    Borrás, Teresa

    2011-01-01

    Gene therapy of the eye has a high potential of becoming the preferred treatment of a number of eye diseases. Because of its easy accessibility, all the tissues of the eye can be reached and genetically manipulated with nowadays standard gene delivery technologies. Gene therapy offers the possibility to do both, correct a genetic defect by replacing the mutated or missing gene and that of using genes as drugs. Gene drugs would be more specific and would have a longer duration of action and less toxicity than conventional drugs. Examples of both applications are beginning to emerge. Using gene replacement, vision has been restored in several patients of Leber congenital amaurosis (Maguire et al., 2009). Some gene drugs, such as siRNA, are currently in clinical trials to silence angiogenic factors in macular degeneration (Campa and Harding, 2011). In this manuscript we first give a short overview of the basics of gene therapy in the eye and then review the ongoing preclinical studies in our laboratory for the gene-drug treatment of steroid-induced ocular hypertension. PMID:23960949

  17. Carotid Body Denervation Prevents the Development of Insulin Resistance and Hypertension Induced by Hypercaloric Diets

    PubMed Central

    Ribeiro, Maria J.; Sacramento, Joana F.; Gonzalez, Constancio; Guarino, Maria P.; Monteiro, Emília C.; Conde, Sílvia V.

    2013-01-01

    Increased sympathetic activity is a well-known pathophysiological mechanism in insulin resistance (IR) and hypertension (HT). The carotid bodies (CB) are peripheral chemoreceptors that classically respond to hypoxia by increasing chemosensory activity in the carotid sinus nerve (CSN), causing hyperventilation and activation of the sympathoadrenal system. Besides its role in the control of ventilation, the CB has been proposed as a glucose sensor implicated in the control of energy homeostasis. However, to date no studies have anticipated its role in the development of IR. Herein, we propose that CB overstimulation is involved in the etiology of IR and HT, core metabolic and hemodynamic disturbances of highly prevalent diseases like the metabolic syndrome, type 2 diabetes, and obstructive sleep apnoea. We demonstrate that CB activity is increased in IR animal models and that CSN resection prevents CB overactivation and diet-induced IR and HT. Moreover, we show that insulin triggers CB, highlighting a new role for hyperinsulinemia as a stimulus for CB overactivation. We propose that CB is implicated in the pathogenesis of metabolic and hemodynamic disturbances through sympathoadrenal overactivation and may represent a novel therapeutic target in these diseases. PMID:23530003

  18. Emission-particle-induced ventilatory abnormalities in a rat model of pulmonary hypertension.

    PubMed

    Gardner, Sarah Y; McGee, John K; Kodavanti, Urmila P; Ledbetter, Allen; Everitt, Jeffrey I; Winsett, Darrell W; Doerfler, Donald L; Costa, Daniel L

    2004-06-01

    Preexistent cardiopulmonary disease in humans appears to enhance susceptibility to the adverse effects of ambient particulate matter. Previous studies in this laboratory have demonstrated enhanced inflammation and mortality after intratracheal instillation (IT) and inhalation (INH) of residual oil fly ash (ROFA) in a rat model of pulmonary hypertension induced by monocrotaline (MCT). The present study was conducted to examine the effects of ROFA in this model on ventilatory function in unanesthetized, unrestrained animals. Sixty-day-old male CD rats were injected with MCT (60 mg/kg) or vehicle (VEH) intraperitoneally 10 days before IT of ROFA (8.3 mg/kg) or saline (SAL) (control) or nose-only INH of ROFA [15 mg/m3 for 6 hr on 3 consecutive days or air (control)]. At 24 and 72 hr after exposure, rats were studied individually in a simultaneous gas uptake/whole-body plethysmograph. Lungs were removed at 72 hr for histology. Pulmonary test results showed that tidal volume (VT) decreased 24 hr after IT of ROFA in MCT-treated rats. Breathing frequency, minute volume (VE), and the ventilatory equivalent for oxygen increased in MCT- and VEH-treated rats 24 hr after IT or INH of ROFA and remained elevated 72 hr post-IT. O2 uptake (VO2) decreased after IT of ROFA in MCT-treated rats. Carbon monoxide uptake decreased 24 hr after IT of ROFA, returning to control values in VEH-treated rats but remaining low in MCT-treated rats 72 hr post-IT. ROFA exposure induced histologic changes and abnormalities in several ventilatory parameters, many of which were enhanced by MCT treatment. PMID:15175175

  19. Hypertension and hypertensive encephalopathy.

    PubMed

    Price, Raymond S; Kasner, Scott E

    2014-01-01

    The definition of hypertension has continuously evolved over the last 50 years. Hypertension is currently defined as a blood pressure greater than 140/90mmHg. One in every four people in the US has been diagnosed with hypertension. The prevalence of hypertension increases further with age, affecting 75% of people over the age of 70. Hypertension is by far the most common risk factor identified in stroke patients. Hypertension causes pathologic changes in the walls of small (diameter<300 microns) arteries and arterioles usually at short branches of major arteries, which may result in either ischemic stroke or intracerebral hemorrhage. Reduction of blood pressure with diuretics, ?-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors have all been shown to markedly reduce the incidence of stroke. Hypertensive emergency is defined as a blood pressure greater than 180/120mmHg with end organ dysfunction, such as chest pain, shortness of breath, encephalopathy, or focal neurologic deficits. Hypertensive encephalopathy is believed to be caused by acute failure of cerebrovascular autoregulation. Hypertensive emergency is treated with intravenous antihypertensive agents to reduce blood pressure by 25% within the first hour. Selective inhibition of cerebrovascular blood vessel permeability for the treatment of hypertensive emergency is beginning early clinical trials. PMID:24365295

  20. Protein restriction during pregnancy induces hypertension and impairs endothelium-dependent vascular function in adult female offspring.

    PubMed

    Sathishkumar, Kunju; Elkins, Rebekah; Yallampalli, Uma; Yallampalli, Chandra

    2009-01-01

    Intrauterine undernutrition plays a role in the development of adult hypertension. Most studies are done in male offspring to delineate the mechanisms whereby blood pressure may be raised; however, the vascular mechanisms involved in female offspring are unclear. Female offspring of pregnant Sprague-Dawley rats fed either a control (C; 18%) or a low-protein (LP; 6%) diet during pregnancy were used. Birth weight and later growth were markedly lower in LP than in C offspring. LP offspring exhibited impaired estrous cyclicity with increased mean arterial pressure. Hypotensive response to acetylcholine (ACh) and the hypertensive response to phenylephrine (PE) were greater in LP than in C rats. N-nitro-L-arginine methyl ester (L-NAME) induced greater hypertensive responses in C than in LP rats. Endothelium-intact mesenteric arteries from LP offspring exhibited increased contractile responses to PE and reduced vasodilation in response to ACh. In endothelium-denuded arteries, relaxation responses to sodium nitroprusside were similar in both groups. Basal and ACh-induced increase in vascular nitrite/nitrate production was lower in LP than in C offspring. L-NAME or 1H-1,2,4-oxadiazolo-4,3-quinoxalin-1-one inhibited ACh relaxations and enhanced PE contractions in C offspring, but had minimal effect in LP rats. The decreased NO-mediated vascular response might explain the increased vascular contraction and arterial pressure in female offspring with low birth weight. PMID:18957856

  1. Optical cryoimaging of rat kidney and the effective role of chromosome 13 in salt-induced hypertension

    NASA Astrophysics Data System (ADS)

    Salehpour, F.; Yang, C.; Kurth, T.; Cowley, A. W.; Ranji, M.

    2015-03-01

    The objective of this work is to assess oxidative stress levels in salt-sensitive hypertension animal model using 3D optical cryoimager to image mitochondrial redox ratio. We studied Dahl salt-induced (SS) rats, and compared the results with a consomic SS rat strain (SSBN13). The SSBN13 strain was developed by the introgression of chromosome from the Brown Norway (BN) rat into the salt-sensitive (SS) genetic background and exhibits significant protection from salt induced hypertension1 . These two groups were fed on a high salt diet of 8.0% NaCl for one week. Mitochondrial redox ratio (NADH/FAD=NADH RR), was used as a quantitative marker of the oxidative stress in kidney tissue. Maximum intensity projected images and their corresponding histograms in each group were acquired from each kidney group. The result showed a 49% decrease in mitochondrial redox ratio of SS compared to SSBN13 translated to an increase in the level of oxidative stress of the tissue. Therefore, the results quantify oxidative stress levels and its effect on mitochondrial redox in salt sensitive hypertension.

  2. Hypothalamic signaling mechanisms in hypertension.

    PubMed

    Carmichael, Casey Y; Wainford, Richard D

    2015-05-01

    The etiology of hypertension, a critical public health issue affecting one in three US adults, involves the integration of the actions of multiple organ systems, including the central nervous system. Increased activation of the central nervous system, driving enhanced sympathetic outflow and increased blood pressure, has emerged as a major contributor to the pathogenesis of hypertension. The hypothalamus is a key brain site acting to integrate central and peripheral inputs to ultimately impact blood pressure in multiple disease states that evoke hypertension. This review highlights recent advances that have identified novel signal transduction mechanisms within multiple hypothalamic nuclei (e.g., paraventricular nucleus, arcuate nucleus) acting to drive the pathophysiology of hypertension in neurogenic hypertension, angiotensin II hypertension, salt-sensitive hypertension, chronic intermittent hypoxia, and obesity-induced hypertension. Increased understanding of hypothalamic activity in hypertension has the potential to identify novel targets for future therapeutic interventions designed to treat hypertension. PMID:25860531

  3. Inhibition of farnesyl pyrophosphate synthase prevents norepinephrine-induced fibrotic responses in vascular smooth muscle cells from spontaneously hypertensive rats.

    PubMed

    Du, Chang-Qing; Yang, Lin; Yang, Jian; Han, Jie; Hu, Xiao-Sheng; Wu, Tao; Hu, Shen-Jiang

    2014-01-01

    Both norepinephrine (NE) and connective tissue growth factor (CTGF) contribute to vascular fibrosis during hypertension. Recent studies indicate that farnesyl pyrophosphate synthase (FPPS) plays an important role in cardiac remodeling in hypertension. However, the role of FPPS in NE-induced fibrotic responses and related molecular mechanisms is unknown. Vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were stimulated with NE. The fibrotic responses were assessed by measuring CTGF, hydroxyproline (hyp), and ?-1 procollagen I levels using Western blot, a hydroxyproline test kit, and real-time quantitative PCR assays, respectively. Ras activity was determined by a pull-down assay using a Ras activation assay kit and detected by Western blot. NE dose-dependently increased fibrosis in SHR-VSMCs, and this increase was significantly reduced by ibandronate, an inhibitor of FPPS. The addition of farnesol, but not geranylgeraniol, partially reversed the inhibitory effects of ibandronate. Furthermore, the anti-fibrotic effects of ibandronate could be mimicked by FTI-276 but not by GGTI-286. A pull-down assay showed that ibandronate reduced the NE-induced Ras activation. Moreover, ibandronate inhibited the NE-induced activation of p38, JNK, and ERK1/2. Only SB203580 (specific inhibitor of p38) diminished the NE-induced CTGF production. These results demonstrated that inhibiting FPPS prevents NE-induced fibrotic responses in SHR-VSMCs and that the Ras kinase and p38 pathways were the underlying mechanisms involved in this process. PMID:23985701

  4. Supplementation of DETA/NO attenuates cold stress induced pulmonary hypertension syndrome in broilers

    E-print Network

    Thompson, Michel Ann

    2002-01-01

    The anatomical and physiological structure of avians increases the broiler chicken's susceptibility to pulmonary hypertension syndrome (PHS). This has been a continual problem in the poultry industry costing millions of dollars annually. Studies...

  5. Protective actions of estrogen on angiotensin II-induced hypertension: role of central nitric oxide.

    PubMed

    Xue, Baojian; Singh, Minati; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2009-11-01

    The present study tested the hypotheses that 1) nitric oxide (NO) is involved in attenuated responses to ANG II in female mice, and 2) there is differential expression of neuronal NO synthase (nNOS) in the subfornical organ (SFO) and paraventricular nucleus (PVN) in response to systemic infusions of ANG II in males vs. females. Aortic blood pressure (BP) was measured in conscious mice with telemetry implants. N(G)-nitro-l-arginine methyl ester (l-NAME; 100 microg x kg(.-1)day(-1)), an inhibitor of NOS, was administrated into the lateral cerebral ventricle for 14 days before and during ANG II pump implantation. Central infusion of l-NAME augmented the pressor effects of systemic ANG II in females (Delta21.5 + or - 2.2 vs. Delta9.2 + or - 1.5 mmHg) but not in males (Delta29.4 + or - 2.5 vs. Delta30.1 + or - 2.5 mmHg). Central administration of N(5)-(1-imino-3-butenyl)-l-ornithine (l-VNIO), a selective nNOS inhibitor, also significantly potentiated the increase in BP induced by ANG II in females (Delta17.5 + or - 3.2 vs. Delta9.2 + or - 1.5 mmHg). In gonadectomized mice, central l-NAME infusion did not affect the pressor response to ANG II in either males or females. Ganglionic blockade after ANG II infusion resulted in a greater reduction in BP in central l-NAME- or l-VNIO-treated females compared with control females. Western blot analysis of nNOS protein expression indicated that levels were approximately 12-fold higher in both the SFO and PVN of intact females compared with those in intact males. Seven days of ANG II treatment resulted in a further increase in nNOS protein expression only in intact females (PVN, to approximately 51-fold). Immunohistochemical studies revealed colocalization of nNOS and estrogen receptors in the SFO and PVN. These results suggest that NO attenuates the increase in BP induced by ANG II through reduced sympathetic outflow in females and that increased nNOS protein expression associated with the presence of female sex hormones plays a protective role against ANG II-induced hypertension in female mice. PMID:19734362

  6. Endogenous hydrogen peroxide in the hypothalamic paraventricular nucleus regulates neurohormonal excitation in high salt-induced hypertension.

    PubMed

    Zhang, Meng; Qin, Da-Nian; Suo, Yu-Ping; Su, Qing; Li, Hong-Bao; Miao, Yu-Wang; Guo, Jing; Feng, Zhi-Peng; Qi, Jie; Gao, Hong-Li; Mu, Jian-Jun; Zhu, Guo-Qing; Kang, Yu-Ming

    2015-06-15

    Reactive oxygen species (ROS) in the brain plays an important role in the progression of hypertension and hydrogen peroxide (H2O2) is a major component of ROS. The aim of this study is to explore whether endogenous H2O2 changed by polyethylene glycol-catalase (PEG-CAT) and aminotriazole (ATZ) in the hypothalamic paraventricular nucleus (PVN) regulates neurotransmitters, renin-angiotensin system (RAS), and cytokines, and whether subsequently affects the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in high salt-induced hypertension. Male Sprague-Dawley rats received a high-salt diet (HS, 8% NaCl) or a normal-salt diet (NS, 0.3% NaCl) for 10 weeks. Then rats were treated with bilateral PVN microinjection of PEG-CAT (0.2 i.u./50nl), an analog of endogenous catalase, the catalase inhibitor ATZ (10nmol/50nl) or vehicle. High salt-fed rats had significantly increased MAP, RSNA, plasma norepinephrine (NE) and pro-inflammatory cytokines (PICs). In addition, rats with high-salt diet had higher levels of NOX-2, NOX-4 (subunits of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), interleukin-1beta (IL-1?), glutamate and NE, and lower levels of gamma-aminobutyric acid (GABA) and interleukin-10 (IL-10) in the PVN than normal diet rats. Bilateral PVN microinjection of PEG-CAT attenuated the levels of RAS and restored the balance of neurotransmitters and cytokines, while microinjection of ATZ into the PVN augmented those changes occurring in hypertensive rats. Our findings demonstrate that ROS component H2O2 in the PVN regulating MAP and RSNA are partly due to modulate neurotransmitters, renin-angiotensin system, and cytokines within the PVN in salt-induced hypertension. PMID:25891026

  7. CNS neuroplasticity and salt-sensitive hypertension induced by prior treatment with subpressor doses of ANG II or aldosterone

    PubMed Central

    Clayton, Sarah C.; Zhang, Zhongming; Beltz, Terry; Xue, Baojian

    2014-01-01

    Although sensitivity to high dietary NaCl is regarded to be a risk factor for cardiovascular disease, the causes of salt-sensitive hypertension remain elusive. Previously, we have shown that rats pretreated with subpressor doses of either ANG II or aldosterone (Aldo) show sensitized hypertensive responses to a mild pressor dose of ANG II when tested after an intervening delay. The current studies investigated whether such treatments will induce salt sensitivity. In studies employing an induction-delay-expression experimental design, male rats were instrumented for chronic mean arterial pressure (MAP) recording. In separate experiments, ANG II, Aldo, or vehicle was delivered either subcutaneously or intracerebroventricularly during the induction. There were no sustained differences in BP during the delay prior to being given 2% saline. While consuming 2% saline during the expression, both ANG II- and Aldo-pretreated rats showed significantly greater hypertension. When hexamethonium was used to assess autonomic control of MAP, no differences in the decrease of MAP in response to ganglionic blockade were detected during the induction. However, during the expression, the fall was greater in sensitized rats. In separate experiments, brain tissue that was collected at the end of delay showed increases in message or activation of putative markers of neuroplasticity (i.e., brain-derived neurotrophic factor, p38 mitogen-activated protein kinase, and cAMP response element-binding protein). These experiments demonstrate that prior administration of nonpressor doses of either ANG II or Aldo will induce salt sensitivity. Collectively, our findings indicate that treatment with subpressor doses of ANG II and Aldo initiate central neuroplastic changes that are involved in hypertension of different etiologies. PMID:24694383

  8. Beneficial effects of Acer okamotoanum sap on L-NAME-induced hypertension-like symptoms in a rat model.

    PubMed

    Yang, Hyun; Hwang, Inho; Koo, Tae-Hyoung; Ahn, Hyo-Jin; Kim, Sun; Park, Mi-Jin; Choi, Won-Sil; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

    2012-02-01

    The sap of Acer okamotoanum has been termed 'bone-benefit-water' in Korea owing to its mineral and sugar content. In particular, the calcium (Ca) and potassium (K) concentrations of the sap of Acer okamotoanum are 40- and 20-times higher, respectively, than commercial spring water. In the present study, we examined whether Acer okamotoanum sap improves or prevents hypertension-like symptoms in a rat model. Male Sprague-Dawley rats (8-weeks-old) were provided commercial spring water supplemented with 25, 50 or 100% Acer okamotoanum sap, 3% potassium ions (K+) or captopril, and treated daily for 2 weeks with NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg/day) by subcutaneous injection, in order to induce hypertensive symptoms. Rats were euthanized 6 h following the final injection. To assess the effect of the sap on hypertension-like symptoms, we examined the mean blood pressure (BP), protein levels and localization of endothelial nitric oxide synthase (eNOS) in the descending aorta of the rats. BP levels were significantly lower in hypertensive rats received 25, 50 and 100% sap compared with rats who were administered only commercial spring water. Protein levels of eNOS were repressed in L-NAME-only-treated rats, but were elevated in the descending aorta of rats administered captopril, K+ water and Acer okamotoanum sap (25, 50 and 100%) up to the level of the sham group provided commercial spring water, and then injected with dimethyl sulfoxide for the same period of time. Localized eNOS protein was abundantly expressed in the perivascular descending aorta adipose tissue of the rats. Taken together, these results demonstrated that the sap of Acer okamotoanum ameliorated high BP induced by L-NAME treatment in a rat model. PMID:22051897

  9. Expression profiling of laser-microdissected intrapulmonary arteries in hypoxia-induced pulmonary hypertension

    PubMed Central

    Kwapiszewska, Grazyna; Wilhelm, Jochen; Wolff, Stephanie; Laumanns, Isabel; Koenig, Inke R; Ziegler, Andreas; Seeger, Werner; Bohle, Rainer M; Weissmann, Norbert; Fink, Ludger

    2005-01-01

    Background Chronic hypoxia influences gene expression in the lung resulting in pulmonary hypertension and vascular remodelling. For specific investigation of the vascular compartment, laser-microdissection of intrapulmonary arteries was combined with array profiling. Methods and Results Analysis was performed on mice subjected to 1, 7 and 21 days of hypoxia (FiO2 = 0.1) using nylon filters (1176 spots). Changes in the expression of 29, 38, and 42 genes were observed at day 1, 7, and 21, respectively. Genes were grouped into 5 different classes based on their time course of response. Gene regulation obtained by array analysis was confirmed by real-time PCR. Additionally, the expression of the growth mediators PDGF-B, TGF-?, TSP-1, SRF, FGF-2, TIE-2 receptor, and VEGF-R1 were determined by real-time PCR. At day 1, transcription modulators and ion-related proteins were predominantly regulated. However, at day 7 and 21 differential expression of matrix producing and degrading genes was observed, indicating ongoing structural alterations. Among the 21 genes upregulated at day 1, 15 genes were identified carrying potential hypoxia response elements (HREs) for hypoxia-induced transcription factors. Three differentially expressed genes (S100A4, CD36 and FKBP1a) were examined by immunohistochemistry confirming the regulation on protein level. While FKBP1a was restricted to the vessel adventitia, S100A4 and CD36 were localised in the vascular tunica media. Conclusion Laser-microdissection and array profiling has revealed several new genes involved in lung vascular remodelling in response to hypoxia. Immunohistochemistry confirmed regulation of three proteins and specified their localisation in vascular smooth muscle cells and fibroblasts indicating involvement of different cells types in the remodelling process. The approach allows deeper insight into hypoxic regulatory pathways specifically in the vascular compartment of this complex organ. PMID:16171515

  10. The spontaneously hypertensive rat: an experimental model of sulfur dioxide-induced airways disease.

    PubMed

    Kodavanti, Urmila P; Schladweiler, Mette C; Ledbetter, Allen D; Ortuno, Roselia Villalobos; Suffia, Marie; Evansky, Paul; Richards, Judy H; Jaskot, Richard H; Thomas, Ronald; Karoly, Edward; Huang, Yuh-Chin T; Costa, Daniel L; Gilmour, Peter S; Pinkerton, Kent E

    2006-11-01

    Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation, and mucus hypersecretion, features that are common in bronchitis, emphysema, and often asthma. However, current rodent models do not reflect this human disease. Because genetically predisposed spontaneously hypertensive (SH) rats display phenotypes such as systemic inflammation, hypercoagulation, oxidative stress, and suppressed immune function that are also apparent in COPD patients, we hypothesized that SH rat may offer a better model of experimental bronchitis. We, therefore, exposed SH and commonly used Sprague Dawley (SD) rats (male, 13- to 15-weeks old) to 0, 250, or 350 ppm sulfur dioxide (SO(2)), 5 h/day for 4 consecutive days to induce airway injury. SO(2) caused dose-dependent changes in breathing parameters in both strains with SH rats being slightly more affected than SD rats. Increases in bronchoalveolar lavage fluid (BALF) total cells and neutrophilic inflammation were dose dependent and significantly greater in SH than in SD rats. The recovery was incomplete at 4 days following SO(2) exposure in SH rats. Pulmonary protein leakage was modest in either strain, but lactate dehydrogenase and N-acetyl glucosaminidase activity were increased in BALF of SH rats. Airway pathology and morphometric evaluation of mucin demonstrated significantly greater impact of SO(2) in SH than in SD rats. Baseline differences in lung gene expression pattern suggested marked immune dysregulation, oxidative stress, impairment of cell signaling, and fatty acid metabolism in SH rats. SO(2) effects on these genes were more pronounced in SH than in SD rats. Thus, SO(2) exposure in SH rats may yield a relevant experimental model of bronchitis. PMID:16929007

  11. Hydrogen sulfide attenuates sFlt1-induced hypertension and renal damage by upregulating vascular endothelial growth factor.

    PubMed

    Holwerda, Kim M; Burke, Suzanne D; Faas, Marijke M; Zsengeller, Zsuzsanna; Stillman, Isaac E; Kang, Peter M; van Goor, Harry; McCurley, Amy; Jaffe, Iris Z; Karumanchi, S Ananth; Lely, A Titia

    2014-04-01

    Soluble fms-like tyrosine kinase 1 (sFlt1), a circulating antiangiogenic protein, is elevated in kidney diseases and contributes to the development of preeclampsia. Hydrogen sulfide is a vasorelaxant and proangiogenic gas with therapeutic potential in several diseases. Therefore, we evaluated the potential therapeutic effect and mechanisms of action of hydrogen sulfide in an animal model of sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis created by adenovirus-mediated overexpression of sFlt1 in Sprague-Dawley rats. We injected sFlt1-overexpressing animals intraperitoneally with the hydrogen sulfide-donor sodium hydrosulfide (NaHS) (50 µmol/kg, twice daily) or vehicle (n=7 per group). Treatment with NaHS for 8 days significantly reduced sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis. Measurement of plasma protein concentrations with ELISA revealed a reduction of free plasma sFlt1 and an increase of free plasma vascular endothelial growth factor (VEGF) after treatment with NaHS. Renal VEGF-A mRNA expression increased significantly with NaHS treatment. In vitro, NaHS was proangiogenic in an endothelial tube assay and attenuated the antiangiogenic effects of sFlt1. Stimulation of podocytes with NaHS resulted in both short-term VEGF release (120 minutes) and upregulation of VEGF-A mRNA levels (24 hours). Furthermore, pretreatment of mesenteric vessels with a VEGF receptor 2-neutralizing antibody significantly attenuated NaHS-induced vasodilation. These results suggest that hydrogen sulfide ameliorates sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis in rats by increasing VEGF expression. Further studies are warranted to evaluate the role of hydrogen sulfide as a novel therapeutic agent for vascular disorders such as preeclampsia. PMID:24335973

  12. Hydrogen Sulfide Attenuates sFlt1-Induced Hypertension and Renal Damage by Upregulating Vascular Endothelial Growth Factor

    PubMed Central

    Holwerda, Kim M.; Burke, Suzanne D.; Faas, Marijke M.; Zsengeller, Zsuzsanna; Stillman, Isaac E.; Kang, Peter M.; van Goor, Harry; McCurley, Amy; Jaffe, Iris Z.; Karumanchi, S. Ananth

    2014-01-01

    Soluble fms-like tyrosine kinase 1 (sFlt1), a circulating antiangiogenic protein, is elevated in kidney diseases and contributes to the development of preeclampsia. Hydrogen sulfide is a vasorelaxant and proangiogenic gas with therapeutic potential in several diseases. Therefore, we evaluated the potential therapeutic effect and mechanisms of action of hydrogen sulfide in an animal model of sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis created by adenovirus-mediated overexpression of sFlt1 in Sprague-Dawley rats. We injected sFlt1-overexpressing animals intraperitoneally with the hydrogen sulfide–donor sodium hydrosulfide (NaHS) (50 µmol/kg, twice daily) or vehicle (n=7 per group). Treatment with NaHS for 8 days significantly reduced sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis. Measurement of plasma protein concentrations with ELISA revealed a reduction of free plasma sFlt1 and an increase of free plasma vascular endothelial growth factor (VEGF) after treatment with NaHS. Renal VEGF-A mRNA expression increased significantly with NaHS treatment. In vitro, NaHS was proangiogenic in an endothelial tube assay and attenuated the antiangiogenic effects of sFlt1. Stimulation of podocytes with NaHS resulted in both short-term VEGF release (120 minutes) and upregulation of VEGF-A mRNA levels (24 hours). Furthermore, pretreatment of mesenteric vessels with a VEGF receptor 2–neutralizing antibody significantly attenuated NaHS-induced vasodilation. These results suggest that hydrogen sulfide ameliorates sFlt1-induced hypertension, proteinuria, and glomerular endotheliosis in rats by increasing VEGF expression. Further studies are warranted to evaluate the role of hydrogen sulfide as a novel therapeutic agent for vascular disorders such as preeclampsia. PMID:24335973

  13. Porphyromonas gingivalis-induced alveolar bone loss is accelerated in the stroke-prone spontaneously hypertensive rat.

    PubMed

    Tokutomi, Fumiaki; Wada-Takahashi, Satoko; Sugiyama, Shuta; Toyama, Toshizo; Sato, Takenori; Hamada, Nobushiro; Tsukinoki, Keiichi; Takahashi, Shun-suke; Lee, Masaichi Chang-il

    2015-06-01

    Porphyromonas gingivalis (P. gingivalis) is one of the prominent periodontal pathogens and is the most important bacteria involved in the onset and exacerbation of periodontitis. P. gingivalis is an anaerobic, Gram-negative coccobacillus that plays a role in the progression of periodontal disease by promoting alveolar bone resorption. The aim of the present study was to examine P. gingivalis-induced osteoclastic bone resorption in the stroke-prone spontaneously hypertensive rat (SHRSP), in which oxidative stress induced by reactive oxygen species (ROS) is increased. In the present study, we used animals orally challenged with P. gingivalis as a chronic inflammation model. Horizontal bone loss around the maxillary molars was assessed morphometrically. Animals were divided into four groups: (1) P. gingivalis-non-infected Wister Kyoto Rat (WKY), (2) orally challenged with P. gingivalis WKY (WKY + Pg), (3) P. gingivalis-non-infected SHRSP, and (4) orally challenged with P. gingivalis SHRSP (SHRSP + Pg). Alveolar bone resorption was significantly increased in the orally challenged with P. gingivalis groups, and was accelerated in the SHRSP group. Histological analysis revealed that the infiltration of inflammatory cells was absent in all groups. However, the infiltration of osteoclasts was observed in the SHRSP + Pg and SHRSP groups. We examined P. gingivalis-induced alveolar bone loss in both the SHRSP and WKY. The results obtained demonstrated that P. gingivalis-induced alveolar bone loss would be involved in hypertension and stroke animal model, such as SHRSP and/or periodontal disease. PMID:25824310

  14. New models of pulmonary hypertension based on VEGF receptor blockade-induced endothelial cell apoptosis

    PubMed Central

    Nicolls, Mark R.; Mizuno, Shiro; Taraseviciene-Stewart, Laima; Farkas, Laszlo; Drake, Jennnifer I.; Al Husseini, Aysar; Gomez-Arroyo, Jose G.; Voelkel, Norbert F.; Bogaard, Herman J.

    2012-01-01

    In spite of treatment, severe angioproliferative pulmonary arterial hypertension (PAH) remains a disease characterized by great morbidity and shortened survival. New treatment strategies for patients with PAH are needed, and after drug development, preclinical studies are best conducted in animal models which present with pulmonary angio-obliterative disease and right heart failure. A rat model of severe pulmonary hypertension and right heart failure, described a decade ago, continues to be investigated and provide insight into the nature of the lung vascular lesions and mechanisms of cardiac adaptation to an altered lung circulation. This rat model is based on the combination of VEGF receptor blockade with Su5416 and chronic hypoxia; use of this pulmonary hypertension induction strategy led to developing the concept of apoptosis-dependent compensatory vascular cell growth. Although, often employed in experimental designs, chronic hypoxia is not necessary for the development of angio-obliterative pulmonary hypertension. Left pneumonectomy combined with Su5416 also results in severe pulmonary hypertension in normoxic conditions. Similarly, the immune insufficiency component of severe PAH can be modeled in athymic rats (lacking T-lymphocytes). In these rats housed under normoxic conditions, treatment with the VEGFR receptor blocker results in angioproliferative pulmonary hypertension; cardiopulmonary disease in these animals can be prevented by immune reconstitution of regulatory T-cells (Tregs). Finally, chronic hypoxia can be replaced with another stimulator of HIF-1?: Ovalbumin (Ova). Immunization of rats with Ova increases lung tissue HIF-1? protein expression, and in Su5416-treated rats causes lethal pulmonary hypertension. Finally, we postulate that these models may also be useful for “reverse translation”; that is, the mechanisms of lung vascular cell death and growth and the modifying influences of immune and bone marrow cells that have been identified in the Su5416 VEGFR inhibitor models can be informative about heretofore undescribed processes in human PAH. PMID:23372927

  15. Inhalable delivery of AAV-based MRP4/ABCC4 silencing RNA prevents monocrotaline-induced pulmonary hypertension

    PubMed Central

    Claude, Caroline; Mougenot, Nathalie; Bechaux, Julia; Hadri, Lahouaria; Brockschnieder, Damian; Clergue, Michel; Atassi, Fabrice; Lompré, Anne-Marie; Hulot, Jean-Sébastien

    2015-01-01

    The ATP-binding cassette transporter MRP4 (encoded by ABCC4) regulates membrane cyclic nucleotides concentrations in arterial cells including smooth muscle cells. MRP4/ABCC4 deficient mice display a reduction in smooth muscle cells proliferation and a prevention of pulmonary hypertension in response to hypoxia. We aimed to study gene transfer of a MRP4/ABCC4 silencing RNA via intratracheal delivery of aerosolized adeno-associated virus 1 (AAV1.shMRP4 or AAV1.control) in a monocrotaline-induced model of pulmonary hypertension in rats. Gene transfer was performed at the time of monocrotaline administration and the effect on the development of pulmonary vascular remodeling was assessed 35 days later. AAV1.shMRP4 dose-dependently reduced right ventricular systolic pressure and hypertrophy with a significant reduction with the higher doses (i.e., >1011 DRP/animal) as compared to AAV1.control. The higher dose of AAV1.shMRP4 was also associated with a significant reduction in distal pulmonary arteries remodeling. AAV1.shMRP4 was finally associated with a reduction in the expression of ANF, a marker of cardiac hypertrophy. Collectively, these results support a therapeutic potential for downregulation of MRP4 for the treatment of pulmonary artery hypertension.

  16. A Critical Role of the mTOR/eIF2? Pathway in Hypoxia-Induced Pulmonary Hypertension

    PubMed Central

    Wang, Ai-ping; Li, Xiao-hui; Yang, Yong-mei; Li, Wen-qun; Zhang, Wang; Hu, Chang-ping; Zhang, Zheng; Li, Yuan-jian

    2015-01-01

    Enhanced proliferation of pulmonary arterial vascular smooth muscle cells (PASMCs) is a key pathological component of vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Mammalian targeting of rapamycin (mTOR) signaling has been shown to play a role in protein translation and participate in the progression of pulmonary hypertension. Eukaryotic translation initiation factor-2? (eIF2?) is a key factor in regulation of cell growth and cell cycle, but its role in mTOR signaling and PASMCs proliferation remains unknown. Pulmonary hypertension (PH) rat model was established by hypoxia. Rapamycin was used to treat rats as an mTOR inhibitor. Proliferation of primarily cultured rat PASMCs was induced by hypoxia, rapamycin and siRNA of mTOR and eIF2? were used in loss-of-function studies. The expression and activation of eIF2?, mTOR and c-myc were analyzed. Results showed that mTOR/eIF2? signaling was significantly activated in pulmonary arteries from hypoxia exposed rats and PASMCs cultured under hypoxia condition. Treatment with mTOR inhibitor for 21 days attenuated vascular remodeling, suppressed mTOR and eIF2? activation, inhibited c-myc expression in HPH rats. In hypoxia-induced PASMCs, rapamycin and knockdown of mTOR and eIF2? by siRNA significantly abolished proliferation and increased c-myc expression. These results suggest a critical role of the mTOR/eIF2?pathway in hypoxic vascular remodeling and PASMCs proliferation of HPH. PMID:26120832

  17. Ameliorative Effect of Hydroethanolic Leaf Extract of Byrsocarpus coccineus in Alcohol- and Sucrose-Induced Hypertension in Rats

    PubMed Central

    Akindele, Abidemi J.; Iyamu, Endurance A.; Dutt, Prabhu; Satti, Naresh K.; Adeyemi, Olufunmilayo O.

    2014-01-01

    Hypertension remains a major health problem worldwide considering the prevalence of morbidity and mortality. Plants remain a reliable source of efficacious and better tolerated drugs and botanicals. This study was designed to investigate the effect of the chemo-profiled hydroethanolic leaf extract of Byrsocarpus coccineus in ethanol- and sucrose-induced hypertension. Groups of rats were treated orally (p.o.) with distilled water (10 ml/kg), ethanol (35%; 3 g/kg), sucrose (5-7%), and B. coccineus (100, 200, and 400 mg/kg), and nifedipine together with ethanol and sucrose separately for 8 weeks. At the end of the treatment period, blood pressure and heart rate of rats were determined. Blood was collected for serum biochemical parameters and lipid profile assessment, and the liver, aorta, kidney, and heart were harvested for estimation of in vivo antioxidants and malondialdehyde (MDA). Results obtained in this study showed that B. coccineus at the various doses administered reduced the systolic, diastolic, and arterial blood pressure elevated by ethanol and sucrose. Also, the extract reversed the reduction in catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD) induced by ethanol and sucrose. The level of MDA was reduced compared to the ethanol- and sucrose-induced hypertensive group. With respect to lipid profile, administration of B. coccineus at the various doses reduced the levels of triglycerides, low-density lipoprotein (LDL), cholesterol, and atherogenic indices, compared to the ethanol and sucrose groups. In conclusion the hydroethanolic leaf extract of B. coccineus exerted significant antihypertensive effect and this is probably related to the antioxidant property and improvement of lipid profile observed in this study. PMID:25161923

  18. Central endogenous angiotensin-(1–7) protects against aldosterone/NaCl-induced hypertension in female rats

    PubMed Central

    Zhang, Zhongming; Johnson, Ralph F.; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2013-01-01

    In comparison to male rodents, females are protected against angiotensin (ANG) II- and aldosterone (Aldo)-induced hypertension. However, the mechanisms underlying this protective effect are not well understood. ANG-(1–7) is formed from ANG II by angiotensin-converting enzyme 2 (ACE2) and has an antihypertensive effect in the central nervous system (CNS). The present study tested the hypothesis that central ANG-(1–7) plays an important protective role in attenuating the development of Aldo/NaCl-hypertension in female rats. Systemic infusion of Aldo into intact female rats with 1% NaCl as their sole drinking fluid resulted in a slight increase in blood pressure (BP). Intracerebroventricular (icv) infusion of A-779, an ANG-(1–7) receptor (Mas-R) antagonist, significantly augmented the pressor effects of Aldo/NaCl. In contrast, systemic Aldo/NaCl induced a significant increase in BP in ovariectomized (OVX) female rats, and central infusion of ANG-(1–7) significantly attenuated this Aldo/NaCl pressor effect. The inhibitory effect of ANG-(1–7) on the Aldo/NaCl pressor effect was abolished by concurrent infusion of A-779. RT-PCR analyses showed that there was a corresponding change in mRNA expression of several renin-angiotensin system components, estrogen receptors and an NADPH oxidase subunit in the lamina terminalis. Taken together these results suggest that female sex hormones regulate an antihypertensive axis of the brain renin-angiotensin system involving ACE2/ANG-(1–7)/Mas-R that plays an important counterregulatory role in protecting against the development of Aldo/NaCl-induced hypertension. PMID:23812385

  19. Estrogen regulation of the brain renin-angiotensin system in protection against angiotensin II-induced sensitization of hypertension

    PubMed Central

    Zhang, Zhongming; Beltz, Terry G.; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2014-01-01

    This study investigated sex differences in the sensitization of angiotensin (ANG) II-induced hypertension and the role of central estrogen and ANG-(1–7) in this process. Male and female rats were implanted for telemetered blood pressure (BP) recording. A subcutaneous subpressor dose of ANG II was given alone or concurrently with intracerebroventricular estrogen, ANG-(1–7), an ANG-(1–7) receptor antagonist A-779 or vehicle for 1 wk (induction). After a 1-wk rest (delay), a pressor dose of ANG II was given for 2 wk (expression). In males and ovariectomized females, subpressor ANG II had no sustained effect on BP during induction, but produced an enhanced hypertensive response to the subsequent pressor dose of ANG II during expression. Central administration of estrogen or ANG-(1–7) during induction blocked ANG II-induced sensitization. In intact females, subpressor ANG II treatment produced a decrease in BP during induction and delay, and subsequent pressor ANG II treatment given during expression produced only a slight but significant increase in BP. However, central blockade of ANG-(1–7) by intracerebroventricular infusion of A-779 during induction restored the decreased BP observed in females during induction and enhanced the pressor response to the ANG II treatment during expression. RT-PCR analyses indicated that estrogen given during induction upregulated mRNA expression of the renin-angiotensin system (RAS) antihypertensive components, whereas both central estrogen and ANG-(1–7) downregulated mRNA expression of RAS hypertensive components in the lamina terminalis. The results indicate that females are protected from ANG II-induced sensitization through central estrogen and its regulation of brain RAS. PMID:24858844

  20. Role of the NADPH oxidases in the subfornical organ in angiotensin II-induced hypertension.

    PubMed

    Lob, Heinrich E; Schultz, David; Marvar, Paul J; Davisson, Robin L; Harrison, David G

    2013-02-01

    Reactive oxygen species and the NADPH oxidases contribute to hypertension via mechanisms that remain undefined. Reactive oxygen species produced in the central nervous system have been proposed to promote sympathetic outflow, inflammation, and hypertension, but the contribution of the NADPH oxidases to these processes in chronic hypertension is uncertain. We therefore sought to identify how NADPH oxidases in the subfornical organ (SFO) of the brain regulate blood pressure and vascular inflammation during sustained hypertension. We produced mice with loxP sites flanking the coding region of the NADPH oxidase docking subunit p22(phox). SFO-targeted injections of an adenovirus encoding cre-recombinase markedly diminished p22(phox), Nox2, and Nox4 mRNA in the SFO, as compared with a control adenovirus encoding red-fluorescent protein injection. Increased superoxide production in the SFO by chronic angiotensin II infusion (490 ng/kg min(-1) × 2 weeks) was blunted in adenovirus encoding cre-recombinase-treated mice, as detected by dihydroethidium fluorescence. Deletion of p22(phox) in the SFO eliminated the hypertensive response observed at 2 weeks of angiotensin II infusion compared with control adenovirus encoding red-fluorescent protein-treated mice (mean arterial pressures=97 ± 15 versus 154 ± 6 mm Hg, respectively; P=0.0001). Angiotensin II infusion also promoted marked vascular inflammation, as characterized by accumulation of activated T-cells and other leukocytes, and this was prevented by deletion of the SFO p22(phox). These experiments definitively identify the NADPH oxidases in the SFO as a critical determinant of the blood pressure and vascular inflammatory responses to chronic angiotensin II, and further support a role of reactive oxygen species in central nervous system signaling in hypertension. PMID:23248154

  1. Pulmonary Hypertension

    MedlinePLUS

    ... page from the NHLBI on Twitter. What Is Pulmonary Hypertension? Pulmonary hypertension (PULL-mun-ary HI-per-TEN-shun), or ... symptoms. Rate This Content: NEXT >> August 2, 2011 Pulmonary Hypertension Clinical Trials Clinical trials are research studies that ...

  2. Role of oxidative stress, inflammation, nitric oxide and transforming growth factor-beta in the protective effect of diosgenin in monocrotaline-induced pulmonary hypertension in rats.

    PubMed

    Ahmed, Lamiaa A; Obaid, Al Arqam Z; Zaki, Hala F; Agha, Azza M

    2014-10-01

    Pulmonary hypertension is a progressive disease of various origins that is associated with right ventricular dysfunction. In the present study, the protective effect of diosgenin was investigated in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). Diosgenin (100 mg/kg) was given by oral administration once daily for 3 weeks. At the end of the experiment, mean arterial blood pressure, electrocardiography and echocardiography were recorded. Rats were then sacrificed and serum was separated for determination of total nitrate/nitrite level. Right ventricles and lungs were isolated for estimation of oxidative stress markers, tumor necrosis factor-alpha, total nitrate/nitrite and transforming growth factor-beta contents. Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible nitric oxide synthase protein expression were also determined. Moreover, histological analysis of pulmonary arteries and cardiomyocyte cross-sectional area was performed. Diosgenin treatment provided a significant improvement toward preserving hemodynamic changes and alleviating oxidative stress, inflammatory and apoptotic markers induced by monocrotaline in rats. Furthermore, diosgenin therapy prevented monocrotaline-induced changes in nitric oxide production, endothelial and inducible nitric oxide synthase protein expression as well as histological analysis. These findings support the beneficial effect of diosgenin in pulmonary hypertension induced by monocrotaline in rats. PMID:25062790

  3. Vascular endothelial growth factor inhibitor-induced hypertension: from pathophysiology to prevention and treatment based on long-acting nitric oxide donors.

    PubMed

    Kruzliak, Peter; Novák, Jan; Novák, Miroslav

    2014-01-01

    Hypertension is the most common adverse effect of the inhibitors of vascular endothelial growth factor (VEGF) pathway-based therapy (VEGF pathway inhibitors therapy, VPI therapy) in cancer patients. VPI includes monoclonal antibodies against VEGF, tyrosine kinase inhibitors, VEGF Traps, and so-called aptamers that may become clinically relevant in the future. All of these substances inhibit the VEGF pathway, which in turn causes a decrease in nitric oxide (NO) and an increase in blood pressure, with the consequent development of hypertension and its final events (e.g., myocardial infarction or stroke). To our knowledge, there is no current study on how to provide an optimal therapy for patients on VPI therapy with hypertension. This review summarizes the roles of VEGF and NO in vessel biology, provides an overview of VPI agents, and suggests a potential treatment procedure for patients with VPI-induced hypertension. PMID:24168915

  4. iPLA2? Overexpression in Smooth Muscle Exacerbates Angiotensin II-Induced Hypertension and Vascular Remodeling

    PubMed Central

    Calderon, Lindsay E.; Liu, Shu; Su, Wen; Xie, Zhongwen; Guo, Zhenheng; Eberhard, Wanda; Gong, Ming C.

    2012-01-01

    Objectives Calcium independent group VIA phospholipase A2 (iPLA2?) is up-regulated in vascular smooth muscle cells in some diseases, but whether the up-regulated iPLA2? affects vascular morphology and blood pressure is unknown. The current study addresses this question by evaluating the basal- and angiotensin II infusion-induced vascular remodeling and hypertension in smooth muscle specific iPLA2? transgenic (iPLA2? -Tg) mice. Method and Results Blood pressure was monitored by radiotelemetry and vascular remodeling was assessed by morphologic analysis. We found that the angiotensin II-induced increase in diastolic pressure was significantly higher in iPLA2?-Tg than iPLA2?-Wt mice, whereas, the basal blood pressure was not significantly different. The media thickness and media?lumen ratio of the mesenteric arteries were significantly increased in angiotensin II-infused iPLA2?-Tg mice. Analysis revealed no difference in vascular smooth muscle cell proliferation. In contrast, adenovirus-mediated iPLA2? overexpression in cultured vascular smooth muscle cells promoted angiotensin II-induced [3H]-leucine incorporation, indicating enhanced hypertrophy. Moreover, angiotensin II infusion-induced c-Jun phosphorylation in vascular smooth muscle cells overexpressing iPLA2? to higher levels, which was abolished by inhibition of 12/15 lipoxygenase. In addition, we found that angiotensin II up-regulated the endogenous iPLA2? protein in-vitro and in-vivo. Conclusion The present study reports that iPLA2? up-regulation exacerbates angiotensin II-induced vascular smooth muscle cell hypertrophy, vascular remodeling and hypertension via the 12/15 lipoxygenase and c-Jun pathways. PMID:22363752

  5. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain.

    PubMed

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-Il

    2011-11-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  6. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain

    PubMed Central

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-il

    2011-01-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  7. Captopril attenuates hypertension and renal injury induced by the vascular endothelial growth factor inhibitor sorafenib

    PubMed Central

    Nagasawa, Tasuku; Khan, Abdul Hye; Imig, John D

    2013-01-01

    SUMMARY Vascular endothelial growth factor inhibitors (VEGFi) are known to cause hypertension and renal injury that severely limits their use as an anticancer therapy. We hypothesized that the angiotensin-converting enzyme inhibitor captopril not only prevents hypertension, but also decreases renal injury caused by the VEGFi sorafenib.Rats were administered sorafenib (20 mg/kg per day) alone or in combination with captopril (40 mg/kg per day) for 4 weeks. Sorafenib administration increased blood pressure, which plateaued by day 10.Concurrent treatment with captopril for 4 weeks resulted in a 30 mmHg decrease in blood pressure compared with sorafenib alone (155 ± 5 vs 182 ± 6 mmHg, respectively; P < 0.05). Furthermore, concurrent captopril treatment reduced albuminuria by 50% compared with sorafenib alone (20 ± 8 vs 42 ± 9 mg/day, respectively; P < 0.05) and reduced nephrinuria by eightfold (280 ± 96 vs 2305 ± 665 ?g/day, respectively; P < 0.05). Glomerular injury, thrombotic micro-angiopathy and tubular cast formation were also decreased in captopril-treated rats administered sorafenib. Renal autoregulatory efficiency was determined by evaluating the afferent arteriolar constrictor response to ATP. Sorafenib administration attenuated the vasoconstriction to ATP, whereas concurrent captopril treatment improved ATP reactivity.In conclusion, captopril attenuated hypertension and renal injury and improved renal autoregulatory capacity in rats administered sorafenib. These findings indicate that captopril treatment, in addition to alleviating the detrimental side-effect of hypertension, decreases the renal injury associated with anticancer VEGFi therapies such as sorafenib. PMID:22443474

  8. Protective effects of 10-nitro-oleic acid in a hypoxia-induced murine model of pulmonary hypertension.

    PubMed

    Klinke, Anna; Möller, Annika; Pekarova, Michaela; Ravekes, Thorben; Friedrichs, Kai; Berlin, Matthias; Scheu, Katrin M; Kubala, Lukas; Kolarova, Hana; Ambrozova, Gabriela; Schermuly, Ralph T; Woodcock, Steven R; Freeman, Bruce A; Rosenkranz, Stephan; Baldus, Stephan; Rudolph, Volker; Rudolph, Tanja K

    2014-07-01

    Pulmonary arterial hypertension (PAH) is characterized by adverse remodeling of pulmonary arteries. Although the origin of the disease and its underlying pathophysiology remain incompletely understood, inflammation has been identified as a central mediator of disease progression. Oxidative inflammatory conditions support the formation of electrophilic fatty acid nitroalkene derivatives, which exert potent anti-inflammatory effects. The current study investigated the role of 10-nitro-oleic acid (OA-NO2) in modulating the pathophysiology of PAH in mice. Mice were kept for 28 days under normoxic or hypoxic conditions, and OA-NO2 was infused subcutaneously. Right ventricular systolic pressure (RVPsys) was determined, and right ventricular and lung tissue was analyzed. The effect of OA-NO2 on cultured pulmonary artery smooth muscle cells (PASMCs) and macrophages was also investigated. Changes in RVPsys revealed increased pulmonary hypertension in mice on hypoxia, which was significantly decreased by OA-NO2 administration. Right ventricular hypertrophy and fibrosis were also attenuated by OA-NO2 treatment. The infiltration of macrophages and the generation of reactive oxygen species were elevated in lung tissue of mice on hypoxia and were diminished by OA-NO2 treatment. Moreover, OA-NO2 decreased superoxide production of activated macrophages and PASMCs in vitro. Vascular structural remodeling was also limited by OA-NO2. In support of these findings, proliferation and activation of extracellular signal-regulated kinases 1/2 in cultured PASMCs was less pronounced on application of OA-NO2.Our results show that the oleic acid nitroalkene derivative OA-NO2 attenuates hypoxia-induced pulmonary hypertension in mice. Thus, OA-NO2 represents a potential therapeutic agent for the treatment of PAH. PMID:24521348

  9. Genetic knockdown of estrogen receptor-alpha in the subfornical organ augments ANG II-induced hypertension in female mice.

    PubMed

    Xue, Baojian; Zhang, Zhongming; Beltz, Terry G; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2015-03-15

    The present study tested the hypotheses that 1) ER? in the brain plays a key role in the estrogen-protective effects against ANG II-induced hypertension, and 2) that the subfornical organ (SFO) is a key site where ER? mediates these protective actions. In this study, a "floxed" ER? transgenic mouse line (ER?(flox)) was used to create models in which ER? was knocked down in the brain or just in the SFO. Female mice with ER? ablated in the nervous system (Nestin-ER?(-) mice) showed greater increases in blood pressure (BP) in response to ANG II. Furthermore, females with ER? knockdown specifically in the SFO [SFO adenovirus-Cre (Ad-Cre) injected ER?(flox) mice] also showed an enhanced pressor response to ANG II. Immunohistochemical (IHC), RT-PCR, and Western blot analyses revealed a marked reduction in the expression of ER? in nervous tissues and, in particular, in the SFO. These changes were not present in peripheral tissues in Nestin-ER?(-) mice or Ad-Cre-injected ER?(flox) mice. mRNA expression of components of the renin-angiotensin system in the lamina terminalis were upregulated in Nestin-ER?(-) mice. Moreover, ganglionic blockade on day 7 after ANG II infusions resulted in a greater reduction of BP in Nestin-ER?(-) mice or SFO Ad-Cre-injected mice, suggesting that knockdown of ER? in the nervous system or the SFO alone augments central ANG II-induced increase in sympathetic tone. The results indicate that interfering with the action of estrogen on SFO ER? is sufficient to abolish the protective effects of estrogen against ANG II-induced hypertension. PMID:25552661

  10. [Using zidena in the treatment of erectile dysfunction associated with stress-induced arterial hypertension in workers of locomotive teams].

    PubMed

    Ne?mark, A I; Mel'nik, M A; Razdorskaia, M V

    2011-01-01

    Thirty train drivers with erectile dysfunction (ED) and arterial hypertension were examined : physical examination, blood count, urinalysis, penile laser Doppler flowmetry (LDF). ED severity was assessed by Loran-Segal questionnaire of male copulative function (MCF) and international index of erectile function (IIEF). Zidena was used in a dose 100 mg 30 min before coitus twice a weak. Examinations have detected mild and moderate ED, spastic disorders of penile microcirculation. MCF significant improvement (p < 0.05), rise of IIEF score were seen after 30 days of zidena treatment. A positive trend was observed after 15 days of treatment. LDF registered a significant (p < 0.05) improvement of microcirculation. Tissue hypoxia and ischemia lowered, blood inflow in the system of microcirculation increased. A passive mechanism of blood flow regulation, vasodilation almost corresponded to physiological standards. Administration of zidena in patients with stress-induced hypertension has improved libido, quality and duration of erection, penile microcirculation due to better tissue perfusion with blood, reduction of ischemia and blood congestion in the venules. Duration of coitus increased. PMID:22066237

  11. Acute and chronic antihypertensive effects of Cinnamomum zeylanicum stem bark methanol extract in L-NAME-induced hypertensive rats

    PubMed Central

    2013-01-01

    Background Previous study showed that the aqueous extract of the stem bark of Cinnamomum zeylanicum possesses antihypertensive and vasodilatory properties. The present work investigates the acute and chronic antihypertensive effects of the methanol extract of Cinnamomum zeylanicum stem bark (MECZ) in L-NAME-induced hypertensive rats. Methods The acute antihypertensive effects of MECZ (5, 10 and 20 mg/kg) administered intravenously were evaluated in rats in which acute arterial hypertension has been induced by intravenous administration of L-NAME (20 mg/kg). For chronic antihypertensive effects, animals were treated with L-NAME (40 mg/kg/day) plus the vehicle or L-NAME (40 mg/kg/day) in combination with captopril (20 mg/kg/day) or MECZ (300 mg/kg/day) and compared with control group receiving only distilled water. All drugs were administered per os and at the end of the experiment that lasted for four consecutive weeks, blood pressure was measured by invasive method and blood samples were collected for the determination of the lipid profile. The heart and aorta were collected, weighed and used for both histological analysis and determination of NO tissue content. Results Acute intravenous administration of C. zeylanicum extract (5, 10 and 20 mg/kg) to L-NAME-induced hypertensive rats provoked a long-lasting decrease in blood pressure. Mean arterial blood pressure decreased by 12.5%, 26.6% and 30.6% at the doses of 5, 10 and 20 mg/kg, respectively. In chronic administration, MECZ and captopril significantly prevented the increase in blood pressure and organs’ weights, as well as tissue histological damages and were able to reverse the depletion in NO tissue’s concentration. The MECZ also significantly lower the plasma level of triglycerides (38.1%), total cholesterol (32.1%) and LDL-cholesterol (75.3%) while increasing that of HDL-cholesterol (58.4%) with a significant low atherogenic index (1.4 versus 5.3 for L-NAME group). Conclusion MECZ possesses antihypertensive and organ protective effects that may result from its ability to increase the production of the endogenous NO and/or to regulate dyslipidemia. PMID:23368533

  12. The effect of beta adrenergic blockade on pulmonary hypertension, right ventricular hypertrophy and polycythaemia, induced in rats by intermittent high altitude hypoxia

    Microsoft Academic Search

    B. Oštádal; J. Ressl; D. Urbanová; J. Widimský; J. Procházka; V. Pelouch

    1978-01-01

    Summary Adult male rats were used to study the effect of a beta blocking agent on pulmonary hypertension and right ventricular hypertrophy induced by intermittent high altitude (IHA) hypoxia (8 hr daily, 5 days a week, stepwise up to the simulated altitude of 7000 m). Trimepranol was injected subcutaneously in a single dose of 10 mg\\/kg\\/b.w. one hour before each

  13. Naringenin adds to the protective effect of L-arginine in monocrotaline-induced pulmonary hypertension in rats: favorable modulation of oxidative stress, inflammation and nitric oxide.

    PubMed

    Ahmed, Lamiaa A; Obaid, Al Arqam Z; Zaki, Hala F; Agha, Azza M

    2014-10-01

    The present study was directed to investigate the possible modulatory effect of naringenin when co-administered with L-arginine in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60 mg/kg). L-arginine (500 mg/kg) and naringenin (50 mg/kg) were orally administered daily, alone and in combination, for 3 weeks. Mean arterial blood pressure, electrocardiography and echocardiography were then recorded and rats were sacrificed and serum was separated for determination of total nitrate/nitrite level. Right ventricles and lungs were isolated for estimation of oxidative stress markers, tumor necrosis factor-alpha, total nitrate/nitrite and transforming growth factor-beta. Myeloperoxidase and caspase-3 activities in addition to endothelial and inducible nitric oxide synthase protein expression were also determined. Moreover, histological analysis of pulmonary arteries and cardiomyocyte cross-sectional area was performed. Combined therapy provided a significant improvement in L-arginine protective effect toward preserving hemodynamic changes and alleviating oxidative stress, inflammatory and apoptotic markers induced by monocrotaline treatment. Furthermore, combined therapy prevented monocrotaline-induced changes in endothelial and inducible nitric oxide synthase protein expression as well as histological analysis compared with either treatment alone. In conclusion, naringenin significantly adds to the protective effect of L-arginine in pulmonary hypertension induced by monocrotaline in rats. PMID:24878387

  14. Exercise-Induced Pulmonary Artery Hypertension in a Patient with Compensated Cardiac Disease: Hemodynamic and Functional Response to Sildenafil Therapy

    PubMed Central

    Nikolaidis, Lazaros; Memon, Nabeel

    2015-01-01

    We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization—combined with the use of a symptom-limited, bedside bicycle ergometer—revealed that the patient's exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class. PMID:25873799

  15. High salt-induced hypertension in B2 knockout mice is corrected by the ETA antagonist, A127722

    PubMed Central

    Brochu, I; Houde, M; Desbiens, L; Simard, E; Gobeil, F; Semaan, W; Bkaily, G; D'Orléans-Juste, P

    2013-01-01

    BACKGROUND AND PURPOSE The contribution of endothelin-1 (ET-1) in a B2KO mouse model of a high salt-induced arterial hypertension was investigated. EXPERIMENTAL APPROACH Wild-type (WT) or B2KO mice receiving a normal diet (ND) or a high-salt diet (HSD) were monitored by radiotelemetry up to a maximum of 18 weeks. At the 12th week of diet, subgroups under ND or HSD received by gavage the ETA antagonist A127722 during 5 days. In addition, blood samples were collected and, following euthanasia, the lungs, heart and kidneys were extracted, homogenized and assayed for ET-1 by RIA. In a separate series of experiments, the ETA antagonist, BQ123 was tested against the pressor responses to a NOS inhibitor L-NG-nitroarginine methyl ester (L-NAME) in anaesthetized WT and B2KO mice. KEY RESULTS In B2KO, but not WT mice, 12 weeks of HSD triggered a maximal increase of the mean arterial pressure (MAP) of 19.1 ± 2.8 mmHg, which was corrected by A127722 to MAP levels found in B2KO mice under ND. Significant increases in immunoreactive ET-1 were detected only in the lungs of B2KO mice under HSD. On the other hand, metabolic studies showed that sodium urinary excretion was markedly reduced in B2KO compared with WT mice under ND. Finally, BQ123 (2 mg·kg?1) reduced by 50% the pressor response to L-NAME (2 mg·kg?1) in B2KO, but not WT mice under anaesthesia. CONCLUSIONS AND IMPLICATIONS Our results support the concept that functional B2 receptors oppose high salt-induced increments in MAP, which are corrected by an ETA receptor antagonist in this mouse model of experimental hypertension. PMID:23713522

  16. Water deprivation-induced sodium appetite and differential expression of encephalic c-Fos immunoreactivity in the spontaneously hypertensive rat.

    PubMed

    Pereira-Derderian, Daniela T B; Vendramini, Regina C; Menani, José V; De Luca, Laurival A

    2010-05-01

    The spontaneously hypertensive rat (SHR) has an intense consumption of NaCl solution. Water deprivation (WD) followed by water intake to satiety induces partial rehydration (PR)-the WD-PR protocol-and sodium appetite. In the present work, WD produced similar water intake and no alterations in arterial pressure among spontaneously hypertensive rat (SHR), Wistar-Kyoto, and Holtzman strains. It also increased the number of cells with positive c-Fos immunoreactivity (Fos-IR) in the lamina terminalis and in the hypothalamic supraoptic (SON) and paraventricular (parvocellular, PVNp) nucleus in these strains. The WD and WD-PR produced similar alterations in all strains in serum osmolality and protein, plasma renin activity, and sodium balance. The SHR ingested about 10 times more 0.3 M NaCl than normotensives strains in the sodium appetite test that follows WD-PR. After WD-PR, the Fos-IR persisted, elevated in the lamina terminalis of all strains but notably in the subfornical organ of the SHR. The WD-PR reversed Fos-IR in the SON of all strains and in the PVNp of SHR. It induced Fos-IR in the area postrema and in the nucleus of the solitary tract (NTS), dorsal raphe, parabrachial (PBN), pre-locus coeruleus (pre-LC), suprachiasmatic, and central amygdalar nucleus of all strains. This effect was bigger in the caudal-NTS, pre-LC, and medial-PBN of SHRs. The results indicate that WD-PR increases cell activity in the forebrain and hindbrain areas that control sodium appetite in the rat. They also suggest that increased cell activity in facilitatory brain areas precedes the intense 0.3 M NaCl intake of the SHR in the sodium appetite test. PMID:20200133

  17. Stress-Induced Sodium Excretion, a New Intermediate Phenotype to Study the Early Genetic Etiology of Hypertension?

    PubMed Central

    Ge, Dongliang; Su, Shaoyong; Zhu, Haidong; Dong, Yanbin; Wang, Xiaoling; Harshfield, Gregory A; Treiber, Frank A; Snieder, Harold

    2009-01-01

    Impaired stress-induced pressure natriuresis, i.e., an inadequate increase in urinary sodium excretion (UNaV) in response to a stress-induced blood pressure increase, may lead to the premature development of essential hypertension. To assess the heritability of baseline UNaV, stress UNaV, and the UNaV response to stress (?UNaV = stress UNaV – baseline UNaV), we studied 396 African American (AA) and 494 European American (EA) twins, including monozygotic and dizygotic of same- as well as opposite-sex (mean age: 17.6 ± 3.3; range: 11.9–30.0). Bivariate genetic model fitting was performed to examine the extent to which genetic and environmental factors are common or specific to baseline and stress UNaV. Heritability estimates for ?UNaV can be derived from these bivariate models. All bivariate analyses were performed separately in EAs and AAs, because univariate models for baseline UNaV showed significant ethnic differences in heritability estimates. Best fitting models showed that the heritability of stress UNaV was 0.42 in EAs and 0.58 in AAs. Only 15% and 11% of the total variance could be attributed to genetic factors common to baseline and stress UNaV in EAs and AAs, respectively. After removal of all shared influences with baseline UNaV, heritabilities for stress UNaV were 0.32 in EAs and 0.57 in AAs. Heritability estimates for ?UNaV were 0.36 in EAs and 0.39 in AAs. In summary, this study establishes ?UNaV and stress UNaV as heritable phenotypes that may be used to study the genetic etiology of early hypertension development. PMID:19104006

  18. PHYSIOLOGY, ENDOCRINOLOGY, AND REPRODUCTION Influence of Aminoguanidine, an Inhibitor of Inducible Nitric Oxide Synthase, on the Pulmonary Hypertensive Response to Microparticle Injections in Broilers1

    Microsoft Academic Search

    R. F. Wideman; O. T. Bowen; G. F. Erf; M. E. Chapman

    The pulmonary hypertensive response to pulmonary vascular obstruction caused by intravenously injected microparticles is amplified by pretreatment with N?nitro-L-arginine methyl ester (L-NAME). The L-NAME prevents the synthesis of the potent vasodilator nitric oxide (NO) by inhibiting both the constitutive (endothe- lial NO synthase (eNOS or NOS-3)) and inducible (induc- ibleNOsynthase(iNOSorNOS-2))formsofNOsynthase. In the present study we used the selective iNOS inhibitor

  19. Pulmonary Hypertension Triggered by Lipopolysaccharide in Ascites Susceptible and Resistant Broilers Is Not Amplified by Aminoguanidine, a Specific Inhibitor of Inducible Nitric Oxide Synthase

    Microsoft Academic Search

    O. T. Bowen; G. F. Erf; N. B. Anthony; R. F. Wideman

    Nitric oxide (NO) is a potent pulmonary vasodilator that modulates the pulmonary vasoconstric- tion and pulmonary hypertension (PH) triggered by bac- terial lipopolysaccharide (LPS) in broilers. The amplitude and duration of the LPS-induced PH are markedly en- hanced following pretreatment with N?-nitro-L-arginine methyl ester (L-NAME), which inhibits NO synthesis by both the constitutive (endothelial) and inducible (in- flammatory) forms of

  20. Myocyte morphological characteristics differ between the phases of pulmonary hypertension-induced ventricular hypertrophy and failure.

    PubMed

    Minami, Shunrou; Onodera, Tatsuyuki; Okazaki, Fumiko; Miyazaki, Hidekazu; Ohsawa, Shingo; Mochizuki, Seibu

    2006-07-01

    Pulmonary hypertensive model rats were prepared by treating them with monochrotaline (MCT). Using these model rats, we examined myocyte remodeling in the right ventricle in response to increased right ventricular pressure. Male Sprague-Dawley rats were divided into 2 groups. Group M received MCT and group C received physiological saline. The 2 groups were examined at weeks 2, 5, and 7 after MCT or saline injection, respectively. At week 2, a significant difference in cell form was not observed in either group. At week 5, cell volume and myocyte cross-sectional area (CSA) of the right ventricle in group M were significantly greater than those in group C. At week 7, cell volume, CSA, and cell length of the right ventricle in group M were all significantly greater than those in group C. These results suggest that pulmonary hypertension causes hypertrophy, accompanying the enlargement of CSA in the right ventricle, and that cells lengthen in the phase of right ventricular failure. These results are similar to the changes observed in left ventricular myocytes due to overload pressure. Both right and left ventricular myocytes may share a common mechanism for myocyte remodeling as an adaptive and maladaptive response to increased ventricular pressure. PMID:16960417

  1. Severe Dextran-Induced Anaphylactic Shock during Induction of Hypertension-Hypervolemia-Hemodilution Therapy following Subarachnoid Hemorrhage

    PubMed Central

    Shiratori, Tohru; Sato, Atsushi; Fukuzawa, Masao; Kondo, Naoko; Tanno, Shogo

    2015-01-01

    Dextran is a colloid effective for volume expansion; however, a possible side effect of its use is anaphylaxis. Dextran-induced anaphylactoid reaction (DIAR) is a rare but severe complication, with a small dose of dextran solution sufficient to induce anaphylaxis. An 86-year-old female who underwent clipping for a ruptured cerebral aneurysm was admitted to the intensive care unit. Prophylactic hypertension-hypervolemia-hemodilution therapy was induced for cerebral vasospasm following a subarachnoid hemorrhage. The patient went into severe shock after administration of dextran for volume expansion, and dextran administration was immediately discontinued. The volume administered at that time was only 0.8?mL at the most. After fluid resuscitation with a crystalloid solution, circulatory status began to recover. However, cerebral vasospasm occurred and the patient's neurological condition deteriorated. Five weeks after the shock, she was diagnosed with hypersensitivity to dextran by a skin test. When severe hypotension occurs after dextran administration, appropriate treatments for shock should be performed immediately with discontinuation of dextran solution. Although colloid administration is recommended in some guidelines and researches, it is necessary to consider concerning the indication for volume expansion as well as the risk of colloid administration. PMID:26171255

  2. 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 ...

  3. Perfusion-Cultured Bovine Anterior Segments as an Ex Vivo Model for Studying Glucocorticoid-Induced Ocular Hypertension and Glaucoma

    PubMed Central

    Tovar-Vidales, Tara; Yorio, Thomas; Wordinger, Robert J.; Clark, Abbot F.

    2011-01-01

    Purpose. To determine whether perfusion-cultured bovine anterior segments would be a suitable model for glaucoma research. Methods. Fresh bovine eyes were dissected and sealed on a custom-made acrylic dish with an O-ring. Perfusion medium was infused by a syringe pump at a constant infusion rate of 5 ?L/min. After intraocular pressure (IOP) was stable, bovine eyes were perfused with medium containing either a vehicle control (0.1% ethanol [ETH]) or dexamethasone (DEX) for up to 7 days. IOP was recorded by a pressure transducer and a computerized system. Perfusion medium was collected for Western immunoblot analysis of myocilin (MYOC). Results. The morphology of the bovine trabecular meshwork after perfusion culture was similar to that of freshly dissected, nonperfused bovine eyes. Treatment with DEX elevated IOP in some bovine eyes, whereas others showed little change. The authors analyzed the data from 18 ETH-treated control eyes and defined 2.82 mm Hg as the threshold of ocular hypertension (OHT), which equals mean pressure change + 2× SD. Approximately 40% (12/29) of the bovine eyes were DEX responders, which is very close to the DEX-responsive rates observed in human and monkey eyes. Western blot data showed that DEX treatment induced the expression of the DEX-inducible gene MYOC only in the perfusion-cultured anterior segments with DEX-induced OHT. Conclusions. OHT can be induced by DEX in perfusion-cultured bovine anterior segments. This is a fast, convenient, affordable, and reliable model for studying DEX-induced OHT and the mechanisms of trabecular outflow. PMID:21911581

  4. N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats

    PubMed Central

    2014-01-01

    Background The outcome of patients suffering from pulmonary arterial hypertension (PAH) are predominantly determined by the response of the right ventricle to the increase afterload secondary to high vascular pulmonary resistance. However, little is known about the effects of the current available or experimental PAH treatments on the heart. Recently, inflammation has been implicated in the pathophysiology of PAH. N-acetylcysteine (NAC), a well-known safe anti-oxidant drug, has immuno-modulatory and cardioprotective properties. We therefore hypothesized that NAC could reduce the severity of pulmonary hypertension (PH) in rats exposed to monocrotaline (MCT), lowering inflammation and preserving pulmonary vascular system and right heart function. Methods Saline-treated control, MCT-exposed, MCT-exposed and NAC treated rats (day 14–28) were evaluated at day 28 following MCT for hemodynamic parameters (right ventricular systolic pressure, mean pulmonary arterial pressure and cardiac output), right ventricular hypertrophy, pulmonary vascular morphometry, lung inflammatory cells immunohistochemistry (monocyte/macrophages and dendritic cells), IL-6 expression, cardiomyocyte hypertrophy and cardiac fibrosis. Results The treatment with NAC significantly decreased pulmonary vascular remodeling, lung inflammation, and improved total pulmonary resistance (from 0.71?±?0.05 for MCT group to 0.50?±?0.06 for MCT?+?NAC group, p?

  5. 17?-Oestradiol-induced neuroprotection in the brain of spontaneously hypertensive rats.

    PubMed

    Pietranera, L; Brocca, M E; Roig, P; Lima, A; Garcia-Segura, L M; De Nicola, A F

    2014-05-01

    17?-oestradiol is a powerful neuroprotective factor for the brain abnormalities of spontaneously hypertensive rats (SHR). 17?-Oestradiol, a nonfeminising isomer showing low affinity for oestrogen receptors, is also endowed with neuroprotective effects in vivo and in vitro. We therefore investigated whether treatment with 17?-oestradiol prevented pathological changes of the hippocampus and hypothalamus of SHR. We used 20-week-old male SHR with a blood pressure of approximately 170 mmHg receiving s.c. a single 800 ?g pellet of 17?-oestradiol dissolved in cholesterol or vehicle only for 2 weeks Normotensive Wistar-Kyoto (WKY) rats were used as controls. 17?-Oestradiol did not modify blood pressure, serum prolactin, 17?-oestradiol levels or the weight of the testis and pituitary of SHR. In the brain, we analysed steroid effects on hippocampus Ki67+ proliferating cells, doublecortin (DCX) positive neuroblasts, glial fibrillary acidic protein (GFAP)+ astrocyte density, aromatase immunostaining and brain-derived neurotrophic factor (BDNF) mRNA. In the hypothalamus, we determined arginine vasopressin (AVP) mRNA. Treatment of SHR with 17?-oestradiol enhanced the number of Ki67+ in the subgranular zone and DCX+ cells in the inner granule cell layer of the dentate gyrus, increased BDNF mRNA in the CA1 region and gyrus dentatus, decreased GFAP+ astrogliosis in the CA1 subfield, and decreased hypothalamic AVP mRNA. Aromatase expression was unmodified. By contrast to SHR, normotensive WKY rats were unresponsive to 17?-oestradiol. These data indicate a role for 17?-oestradiol as a protective factor for the treatment of hypertensive encephalopathy. Furthermore, 17?-oestradiol is weakly oestrogenic in the periphery and can be used in males. PMID:24730417

  6. Cigarette Smoke-Induced Emphysema and Pulmonary Hypertension Can Be Prevented by Phosphodiesterase 4 and 5 Inhibition in Mice

    PubMed Central

    Pichl, Alexandra; Bednorz, Mariola; Ghofrani, Hossein Ardeschir; Schermuly, Ralph Theo; Seeger, Werner; Grimminger, Friedrich; Weissmann, Norbert

    2015-01-01

    Rationale Chronic obstructive pulmonary disease (COPD) is a widespread disease, with no curative therapies available. Recent findings suggest a key role of NO and sGC-cGMP signaling for the pathogenesis of the disease. Previous data suggest a downregulation/inactivation of the cGMP producing soluble guanylate cyclase, and sGC stimulation prevented cigarette smoke-induced emphysema and pulmonary hypertension (PH) in mice. We thus aimed to investigate if the inhibition of the cGMP degrading phosphodiesterase (PDE)5 has similar effects. Results were compared to the effects of a PDE 4 inhibitor (cAMP elevating) and a combination of both. Methods C57BL6/J mice were chronically exposed to cigarette smoke and in parallel either treated with Tadalafil (PDE5 inhibitor), Piclamilast (PDE4 inhibitor) or both. Functional measurements (lung compliance, hemodynamics) and structural investigations (alveolar and vascular morphometry) as well as the heart ratio were determined after 6 months of tobacco smoke exposure. In addition, the number of alveolar macrophages in the respective lungs was counted. Results Preventive treatment with Tadalafil, Piclamilast or a combination of both almost completely prevented the development of emphysema, the increase in lung compliance, tidal volume, structural remodeling of the lung vasculature, right ventricular systolic pressure, and right ventricular hypertrophy induced by cigarette smoke exposure. Single, but not combination treatment prevented or reduced smoke-induced increase in alveolar macrophages. Conclusion Cigarette smoke-induced emphysema and PH could be prevented by inhibition of the phosphodiesterases 4 and 5 in mice. PMID:26058042

  7. Inhibition of nuclear factor-?B in the lungs prevents monocrotaline-induced pulmonary hypertension in mice.

    PubMed

    Li, Li; Wei, Chuanyu; Kim, Il-Kwon; Janssen-Heininger, Yvonne; Gupta, Sudhiranjan

    2014-06-01

    Pulmonary arterial hypertension (PAH) is a devastating cardiopulmonary disorder with significant morbidity and mortality in patients with various lung and heart diseases. PAH is characterized by vascular obstruction which leads to a sustained increased pulmonary vascular resistance, vascular remodeling, and right ventricular hypertrophy and failure. Limited PAH therapies indicate that novel approaches are urgently needed for the treatment of PAH. Nuclear factor-?B (NF-?B) has been shown to play an important role in different cardiac pathologies; however, the role of NF-?B remains limited in the setting of PAH. Here, we investigated whether NF-?B inhibition in the lungs using Club (Clara) cell-10 promoter driving I?B? mutant had any effect in monocrotaline (MCT)-induced PAH mouse model. Our data revealed that MCT-induced PAH and right ventricular hypertrophy were associated with NF-?B activation, inflammatory response, and altered expression of bone morphogenetic protein receptor 2, inhibitor of differentiation, and Notch-3 signaling molecules in wild-type mice; and all these alterations were prevented in I?B? mutant mice treated with MCT. Moreover, endothelial cell apoptosis and endothelial-to-mesenchymal transition occurred in the lungs of MCT-treated wild-type mice and were restored in I?B? mutant+MCT mice, indicating an association with NF-?B signaling. In lung microvascular endothelial cells, I?B? (AA) mutant plasmid restored the decreased bone morphogenetic protein receptor 2 protein level and reversed the endothelial-to-mesenchymal transition process induced by transforming growth factor-?1. We conclude that NF-?B regulates bone morphogenetic protein receptor 2-inhibitor of differentiation-Notch-3 axis genes and the subsequent endothelial cell apoptosis and endothelial-to-mesenchymal transition events in the lungs, providing new mechanistic information about MCT-induced PAH and right ventricular hypertrophy. PMID:24614212

  8. 6?-hydroxytestosterone, a cytochrome P450 1B1 metabolite of testosterone, contributes to angiotensin II-induced hypertension and its pathogenesis in male mice.

    PubMed

    Pingili, Ajeeth K; Kara, Mehmet; Khan, Nayaab S; Estes, Anne M; Lin, Zongtao; Li, Wei; Gonzalez, Frank J; Malik, Kafait U

    2015-06-01

    Previously, we showed that Cyp1b1 gene disruption minimizes angiotensin II-induced hypertension and associated pathophysiological changes in male mice. This study was conducted to test the hypothesis that cytochrome P450 1B1-generated metabolites of testosterone, 6?-hydroxytestosterone and 16?-hydroxytestosterone, contribute to angiotensin II-induced hypertension and its pathogenesis. Angiotensin II infusion for 2 weeks increased cardiac cytochrome P450 1B1 activity and plasma levels of 6?-hydroxytestosterone, but not 16?-hydroxytestosterone, in Cyp1b1(+/+) mice without altering Cyp1b1 gene expression; these effects of angiotensin II were not observed in Cyp1b1(-/-) mice. Angiotensin II-induced increase in systolic blood pressure and associated cardiac hypertrophy, and fibrosis, measured by intracardiac accumulation of ?-smooth muscle actin, collagen, and transforming growth factor-?, and increased nicotinamide adenine dinucleotide phosphate oxidase activity and production of reactive oxygen species; these changes were minimized in Cyp1b1(-/-) or castrated Cyp1b1(+/+) mice, and restored by treatment with 6?-hydroxytestoterone. In Cyp1b1(+/+) mice, 6?-hydroxytestosterone did not alter the angiotensin II-induced increase in systolic blood pressure; the basal systolic blood pressure was also not affected by this agent in either genotype. Angiotensin II or castration did not alter cardiac, angiotensin II type 1 receptor, angiotensin-converting enzyme, Mas receptor, or androgen receptor mRNA levels in Cyp1b1(+/+) or in Cyp1b1(-/-) mice. These data suggest that the testosterone metabolite, 6?-hydroxytestosterone, contributes to angiotensin II-induced hypertension and associated cardiac pathogenesis in male mice, most probably by acting as a permissive factor. Moreover, cytochrome P450 1B1 could serve as a novel target for developing agents for treating renin-angiotensin and testosterone-dependent hypertension and associated pathogenesis in males. PMID:25870196

  9. The herbal medicine Toki-shakuyaku-san improves the hypertension and intrauterine growth retardation in preeclampsia rats induced by Nomega-nitro-L-arginine methyl ester.

    PubMed

    Takei, H; Nakai, Y; Hattori, N; Yamamoto, M; Kurauchi, K; Sasaki, H; Aburada, M

    2004-01-01

    The chronic inhibition of nitric oxide (NO) synthesis with Nomega-nitro-L-arginine methyl ester (L-NAME) induces a preeclampsia-like syndrome including hypertension and intrauterine growth retardation (IUGR) in pregnant rats. We tested the traditional herbal medicine Toki-shakuyaku-san (TS) for beneficial effects in this model. L-NAME was infused subcutaneously into pregnant rats from day 14 of gestation. TS (1 g/kg, 2 g/kg) was administered by gavage from day 14 to 20. Systolic blood pressure was measured on day 19. On day 20, rats were sacrificed and serum NO levels, placental weight, fetal body weight, fetal cerebrum weight and the thickness of the cerebral cortex were analyzed. TS (1 g/kg, 2 g/kg) inhibited L-NAME-induced hypertension. The decrease in fetal body weight, cerebrum weight and thickness of the cerebral cortex was abrogated by TS (2 g/kg). The effect of TS on blood pressure was found only in the rats that were both pregnant and infused with L-NAME. L-arginine, at the amount equivalent to that contained in TS, showed no effect. Further, the change in serum NO levels induced by TS was only marginal. TS thus improved the hypertension and IUGR in preeclampsia rats induced by L-NAME in a NO-independent manner. These data suggested that TS may be beneficial for the treatment and prevention of preeclampsia. PMID:14971720

  10. Superoxide Mediates Depressive Effects Induced by Hydrogen Sulfide in Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats

    PubMed Central

    Yu, Haiyun; Xu, Haiyan; Liu, Xiaoni; Zhang, Nana; He, Anqi; Yu, Jerry; Lu, Ning

    2015-01-01

    Hydrogen sulfide (H2S) plays a crucial role in the regulation of blood pressure and oxidative stress. In the present study, we tested the hypothesis that H2S exerts its cardiovascular effects by reducing oxidative stress via inhibition of NADPH oxidase activity in the rostral ventrolateral medulla (RVLM). We examined cell distributions of cystathionine-?-synthase (CBS) and effects of H2S on reactive oxygen species (ROS) and mean arterial blood pressure (MAP) in spontaneously hypertensive rats (SHRs). We found that CBS was expressed in neurons of the RVLM, and the expression was lower in SHRs than in Wistar-Kyoto rats. Microinjection of NaHS (H2S donor), S-adenosyl-l-methionine (SAM, a CBS agonist), or Apocynin (NADPH oxidase inhibitor) into the RVLM reduced the ROS level, NADPH oxidase activity, and MAP, whereas microinjection of hydroxylamine hydrochloride (HA, a CBS inhibitor) increased MAP. Furthermore, intracerebroventricular infusion of NaHS inhibited phosphorylation of p47phox, a key step of NADPH oxidase activation. Since decreasing ROS level in the RVLM reduces MAP and heart rate and increasing H2S reduces ROS production, we conclude that H2S exerts an antihypertensive effect via suppressing ROS production. H2S, as an antioxidant, may be a potential target for cardiovascular diseases.

  11. MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension

    PubMed Central

    Ambler, S. Kelly; Li, Min; Sullivan, Timothy M.; Henry, Lauren N.; Crossno, Joseph T.; Long, Carlin S.; Garrington, Timothy P.; Stenmark, Kurt R.

    2013-01-01

    Pulmonary hypertension (PH) results in pressure overload of the right ventricle (RV) of the heart, initiating pathological RV remodeling and ultimately leading to right heart failure. Substantial research indicates that signaling through the MAPK superfamily mediates pathological cardiac remodeling. These considerations led us to test the hypothesis that the regulatory protein MAPKKK-2 (MEKK2) contributes to RV hypertrophy in hypoxia-induced PH. Transgenic mice with global knockout of MEKK2 (MEKK2?/? mice) and age-matched wild-type (WT) mice were exposed to chronic hypobaric hypoxia (10% O2, 6 wk) and compared with animals under normoxia. Exposure to chronic hypoxia induced PH in WT and MEKK2?/? mice. In response to PH, WT mice showed RV hypertrophy, demonstrated as increased ratio of RV weight to body weight, increased RV wall thickness at diastole, and increased cardiac myocyte size compared with normoxic control animals. In contrast, each of these measures of RV hypertrophy seen in WT mice after chronic hypoxia was attenuated in MEKK2?/? mice. Furthermore, chronic hypoxia elicited altered programs of hypertrophic and inflammatory gene expression consistent with pathological RV remodeling in WT mice; MEKK2 deletion selectively inhibited inflammatory gene expression compared with WT mice. The actions of MEKK2 were mediated in part through regulation of the abundance and phosphorylation of its effector, ERK5. In conclusion, signaling by MEKK2 contributes to RV hypertrophy and altered myocardial inflammatory gene expression in response to hypoxia-induced PH. Therapies targeting MEKK2 may protect the myocardium from hypertrophy and pathological remodeling in human PH. PMID:23125215

  12. The Effects of Hydroalchoholic Extract of Teucrium polium L. on Hypertension Induced by Angiotensin II in Rats

    PubMed Central

    Mahmoudabady, Maryam; Shafei, Mohammad Naser; Niazmand, Saeed; Khodaee, Esmaeel

    2014-01-01

    Background: Antispasmodic and vasorelaxant effects of Teucrium polium L. (TP) were mentioned in former studies, so we attempted to evaluate the eventual preventive effect of TP in an acute experimental model of hypertension induced by angiotensin II (Ang II). Methods: Forty-eight male Wistar rats were divided randomly into six groups (n = 8); control Group (C), which received only saline, group Ang II; which received Ang II (300 ng/min, IV), group losartan (Los); which received Los (10 mg/kg, IV) before Ang II injection, three groups of TP 100, TP 200, and TP 400; which received different doses of TP extract (100, 200 and 400 mg/kg, IP, respectively) before Ang II application. After cannulation of the femoral artery, mean arterial blood pressure (MAP) and heart rate (HR) was continuously measured and recorded during the experiments. Comparisons were performed using t-test with SPSS software, version 16 (SPSS, Chicago, IL). Results: MAP and HR in Ang group were significantly higher than the control group (P < 0.001), MAP in group Los significantly was lower than Ang group (P < 0.001) and pretreatment with three doses of TP extract also inhibited increasing of MAP after Ang II injection (P < 0.001). Los also inhibited the increase of HR due to Ang II (P < 0.001), but none of three doses of TP extract had a protective effect on tachycardia induced by Ang II. Conclusions: It seems TP extract could be effective in preventing of high blood pressure induced by Ang II pathway activation but could not have remarkable efficacy for improving the created tachycardia. PMID:25400883

  13. Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung.

    PubMed

    Ravi, Yazhini; Selvendiran, Karuppaiyah; Naidu, Shan K; Meduru, Sarath; Citro, Lucas A; Bognár, Balázs; Khan, Mahmood; Kálai, Tamás; Hideg, Kálmán; Kuppusamy, Periannan; Sai-Sudhakar, Chittoor B

    2013-03-01

    Pulmonary hypertension (PH) that occurs after left-heart failure (LHF), classified as Group 2 PH, involves progressive pulmonary vascular remodeling induced by smooth muscle cell (SMC) proliferation. However, mechanisms involved in the activation of SMCs remain unknown. The objective of this study was to determine the involvement of peroxynitrite and phosphatase-and-tensin homolog on chromosome 10 (PTEN) in vascular SMC proliferation and remodeling in the LHF-induced PH (LHF-PH). LHF was induced by permanent ligation of left anterior descending coronary artery in rats for 4 weeks. MRI, ultrasound, and hemodynamic measurements were performed to confirm LHF and PH. Histopathology, Western blot, and real-time polymerase chain reaction analyses were used to identify key molecular signatures. Therapeutic intervention was demonstrated using an antiproliferative compound, HO-3867. LHF-PH was confirmed by significant elevation of pulmonary artery pressure (mean pulmonary artery pressure/mm Hg: 35.9±1.8 versus 14.8±2.0, control; P<0.001) and vascular remodeling. HO-3867 treatment decreased mean pulmonary artery pressure to 22.6±0.8 mm Hg (P<0.001). Substantially higher levels of peroxynitrite and significant loss of PTEN expression were observed in the lungs of LHF rats when compared with control. In vitro studies using human pulmonary artery SMCs implicated peroxynitrite-mediated downregulation of PTEN expression as a key mechanism of SMC proliferation. The results further established that HO-3867 attenuated LHF-PH by decreasing oxidative stress and increasing PTEN expression in the lung. In conclusion, peroxynitrite and peroxynitrite-mediated PTEN inactivation seem to be key mediators of lung microvascular remodeling associated with PH secondary to LHF. PMID:23339168

  14. Pulmonary Hypertension Secondary to Left-heart Failure Involves Peroxynitrite-induced Downregulation of PTEN in the Lung

    PubMed Central

    Ravi, Yazhini; Selvendiran, Karuppaiyah; Naidu, Shan K.; Meduru, Sarath; Citro, Lucas A.; Bognár, Balázs; Khan, Mahmood; Kálai, Tamás; Hideg, Kálmán; Kuppusamy, Periannan; Sai-Sudhakar, Chittoor B.

    2013-01-01

    Pulmonary hypertension (PH) that occurs after left-heart failure (LHF), classified as Group 2 PH, involves progressive pulmonary vascular remodeling induced by smooth muscle cell (SMC) proliferation. However, mechanisms involved in the activation of SMCs remain unknown. The objective of this study was to determine the involvement of peroxynitrite and phosphatase-and-tensin homolog on chromosome 10 (PTEN) in vascular SMC proliferation and remodeling in the LHF-induced PH (LHF-PH). LHF was induced by permanent ligation of left anterior descending coronary artery in rats for 4 weeks. MRI, ultrasound, and hemodynamic measurements were performed to confirm LHF and PH. Histopathology, western blot, and real-time polymerase chain reaction analyses were used to identify key molecular signatures. Therapeutic intervention was demonstrated using an antiproliferative compound, HO-3867. LHF-PH was confirmed by significant elevation of mean pulmonary artery pressure (mean pulmonary artery pressure/mm?Hg: 35.9±1.8 versus 14.8±2.0, control; P<0.001) and vascular remodeling. HO-3867 treatment decreased mean pulmonary artery pressure to 22.6±0.8 mm?Hg (P<0.001). Substantially higher levels of peroxynitrite and significant loss of PTEN expression were observed in the lungs of LHF rats when compared with control. In vitro studies using human pulmonary artery SMCs implicated peroxynitrite-mediated downregulation of PTEN expression as a key mechanism of SMC proliferation. The results further established that HO-3867 attenuated LHF-PH by decreasing oxidative stress and increasing PTEN expression in the lung. In conclusion, peroxynitrite and peroxynitrite-mediated PTEN inactivation seem to be key mediators of lung microvascular remodeling associated with PH secondary to LHF. PMID:23339168

  15. Fasudil reversed MCT-induced and chronic hypoxia-induced pulmonary hypertension by attenuating oxidative stress and inhibiting the expression of Trx1 and HIF-1?.

    PubMed

    Liu, Manling; Wang, Yanxia; Zheng, Lianhe; Zheng, Wansong; Dong, Kai; Chen, Shuai; Zhang, Bo; Li, Zhichao

    2014-09-15

    Antioxidant therapy attenuates pulmonary hypertension (PH). In the present study, we tested the antioxidant effects of fasudil against PH in rats. Monocrotaline (MCT)-induced and chronic hypoxia-induced PH models of rats were established, and the haemodynamic and pathomorphologic results of three different doses of fasudil (10 mg/kg, 30 mg/kg, and 75 mg/kg per day) were subsequently compared with those of bosentan (30 mg/kg per day). Additionally, the protein expressions of thioredoxin-1 (Trx1) and hypoxia inducible factor-1? (HIF-1?), the content of superoxide dismutase (SOD), and the levels of hydrogen peroxide (H2O2), malonyldialdehyde (MDA), and hydroxy radical (·OH) were investigated. Fasudil effectively reduced the right ventricular systolic pressure (RVSP) and alleviated right ventricle (RV) hypertrophy, as well as the histological changes in the pulmonary arterioles. Moreover, fasudil markedly lessened the expression of Trx1 and HIF-1?, up-regulated the concentration of SOD, and lowered the levels of H2O2, MDA, and ·OH. In conclusion, fasudil is a notably attractive potential therapy for PH. PMID:24973470

  16. An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension

    Microsoft Academic Search

    Toshinori Omi; Maki Kumada; Toyomi Kamesaki; Hiroshi Okuda; Lkhagvasuren Munkhtulga; Yoshiko Yanagisawa; Nanami Utsumi; Takaya Gotoh; Akira Hata; Masayoshi Soma; Satoshi Umemura; Toshio Ogihara; Norio Takahashi; Yasuharu Tabara; Kazuyuki Shimada; Hiroyuki Mano; Eiji Kajii; Tetsuro Miki; Sadahiko Iwamoto

    2006-01-01

    Cold-induced autoinflammatory syndrome 1 (CIAS1) gene is a member of the NALP subfamily of the CATERPILLER protein family that is expressed predominantly in peripheral blood leukocytes, which is to regulate apoptosis or inflammation through the activation of NF-?B and caspase. Recent genetic analyses suggested an association between inflammation and oxidative stress-related genes in the development of hypertension. This is the

  17. Systemic hypertension induced by hepatic overexpression of human preproendothelin-1 in rats.

    PubMed Central

    Niranjan, V; Télémaque, S; deWit, D; Gerard, R D; Yanagisawa, M

    1996-01-01

    Endothelin-1 (ET-1) has been implicated in the regulation of vascular tone in various pathological conditions. To examine the effect of in vivo overexpression of the peptide in rats, we prepared recombinant adenovirus stocks encoding the human preproET-1 cDNA (Ad.ET-1) or Escherichia coli lacZ (Ad.betaGal), each driven by cytomegalovirus early promoter. Ad.ET-1 or Ad.betaGal was injected into the caudal vein of rats and the animals were studied under anesthesia 96 h later. Hepatic overexpression of the virus-derived human ET-1 mRNA was accompanied by a 13-fold elevation of liver ET-1 content in the Ad.ET-1 group. Circulating plasma ET-1 levels in the Ad.ET-1 group were sixfold higher than those in the Ad.betaGal group. Mean arterial blood pressure was increased by 28 mmHg in the Ad.ET-1 group as compared with the Ad.betaGal group. In the Ad.ET-1 group, intravenous infusion of the ET(A) receptor antagonist FR 139317 reduced the blood pressure to levels seen in the Ad.betaGal group, whereas the same antagonist did not significantly alter the blood pressure in the Ad.betaGal group. Intravenous infusion of the ET(B) receptor antagonist BQ-788 caused a small but significant increase in blood pressure in both groups. These findings demonstrate that endogenous overexpression of preproET-1, accompanied by an elevation of plasma ET-1 concentrations to the levels seen in pathophysiological states, can cause systemic hypertension through the activation of the ETA receptor. PMID:8941655

  18. Postinfarction Survival and Inducibility of Ventricular Arrhythmias in the Spontaneously Hypertensive Rat Effects of Ramipril and Hydralazine

    Microsoft Academic Search

    Tan Nguyen; Jean L. Rouleau

    2010-01-01

    Background—Hypertensive patients with left ventricular hypertrophy (LVH) have been found to have greater peri- infarction and postinfarction mortality. In this study, we evaluated the postinfarction survival, susceptibility to ventricular arrhythmias, and degree of LVH and cardiac fibrosis in the spontaneously hypertensive rat (SHR) and the effects of the ACE inhibitor ramipril and the direct vasodilator hydralazine on these characteristics. Methods

  19. Candidate genes in quantitative trait loci associated with absolute and relative kidney weight in rats with Inherited Stress Induced Arterial Hypertension

    PubMed Central

    2015-01-01

    Background The kidney mass is significantly increased in hypertensive ISIAH rats with Inherited Stress Induced Arterial Hypertension as compared with normotensive WAG rats. The QTL/microarray approach was carried out to determine the positional candidate genes in the QTL for absolute and relative kidney weight. Results Several known and predicted genes differentially expressed in ISIAH and WAG kidney were mapped to genetic loci associated with the absolute and relative kidney weight in 6-month old F2 hybrid (ISIAHxWAG) males. The knowledge-driven filtering of the list of candidates helped to suggest several positional candidate genes, which may be related to the structural and mass changes in hypertensive ISIAH kidney. In the current study, we showed that all loci found for absolute and relative kidney weight didn't overlap with significant or suggestive loci for arterial blood pressure level. So, the genes differentially expressed in ISIAH and WAG kidneys and located in these QTL regions associated with absolute and relative kidney weight shouldn't substantially influence the BP level in the 6 month-old ISIAH rats. However, in some cases, small effects may be suggested. Conclusions The further experimental validation of causative genes and detection of polymorphisms will provide opportunities to advance our understanding of the underlying nature of structural and mass changes in hypertensive ISIAH kidney. PMID:25707311

  20. Mineralocorticoid hypertension

    PubMed Central

    Gupta, Vishal

    2011-01-01

    Hypertension affects about 10 – 25% of the population and is an important risk factor for cardiovascular and renal disease. The renin-angiotensin system is frequently implicated in the pathophysiology of hypertension, be it primary or secondary. The prevalence of primary aldosteronism increases with the severity of hypertension, from 2% in patients with grade 1 hypertension to 20% among resistant hypertensives. Mineralcorticoid hypertension includes a spectrum of disorders ranging from renin-producing pathologies (renin-secreting tumors, malignant hypertension, coarctation of aorta), aldosterone-producing pathologies (primary aldosteronism – Conns syndrome, familial hyperaldosteronism 1, 2, and 3), non-aldosterone mineralocorticoid producing pathologies (apparent mineralocorticoid excess syndrome, Liddle syndrome, deoxycorticosterone-secreting tumors, ectopic adrenocorticotropic hormones (ACTH) syndrome, congenitalvadrenal hyperplasia), and drugs with mineraocorticoid activity (locorice, carbenoxole therapy) to glucocorticoid receptor resistance syndromes. Clinical presentation includes hypertension with varying severity, hypokalemia, and alkalosis. Ratio of plasma aldosterone concentraion to plasma renin activity remains the best screening tool. Bilateral adrenal venous sampling is the best diagnostic test coupled with a CT scan. Treatment is either surgical (adrenelectomy) for unilateral adrenal disease versus medical therapy for idiopathic, ambiguous, or bilateral disease. Medical therapy focuses on blood pressure control and correction of hypokalemia using a combination of anti-hypertensives (calcium channel blockers, angiotensin converting enzyme inhibitors, or angiotensin receptor blockers) and potassium-raising therapies (mineralcorticoid receptor antagonist or potassium sparing diuretics). Direct aldosterone synthetase antagonists represent a promising future therapy. PMID:22145132

  1. Rats with adenine-induced chronic renal failure develop low-renin, salt-sensitive hypertension and increased aortic stiffness.

    PubMed

    Nguy, Lisa; Johansson, Maria E; Grimberg, Elisabeth; Lundgren, Jaana; Teerlink, Tom; Carlström, Mattias; Lundberg, Jon O; Nilsson, Holger; Guron, Gregor

    2013-05-01

    Rats with adenine-induced chronic renal failure (A-CRF) develop metabolic and cardiovascular abnormalities resembling those in patients with chronic kidney disease. The aim of this study was to investigate the mechanisms of hypertension in this model and to assess aortic stiffness in vivo. Male Sprague-Dawley rats were equipped with radiotelemetry probes for arterial pressure recordings and received either chow containing adenine or normal control diet. At 7 to 11 wk after study start, blood pressure responses to high NaCl (4%) diet and different pharmacological interventions were analyzed. Aortic pulse wave velocity was measured under isoflurane anesthesia. Baseline 24-h mean arterial pressure (MAP) was 101 ± 10 and 119 ± 9 mmHg in controls and A-CRF animals, respectively (P < 0.01). After 5 days of a high-NaCl diet, MAP had increased by 24 ± 6 mmHg in A-CRF animals vs. 2 ± 1 mmHg in controls (P < 0.001). Candesartan (10 mg/kg by gavage) produced a more pronounced reduction of MAP in controls vs. A-CRF animals (-12 ± 3 vs. -5 ± 5 mmHg, P < 0.05). Aortic pulse wave velocity was elevated in A-CRF rats (5.10 ± 0.51 vs. 4.58 ± 0.17 m/s, P < 0.05). Plasma levels of creatinine were markedly elevated in A-CRF animals (259 ± 46 vs. 31 ± 2 ?M, P < 0.001), whereas plasma renin activity was suppressed (0.6 ± 0.5 vs. 12.3 ± 7.3 ?g·l(-1)·h(-1), P < 0.001). In conclusion, hypertension in A-CRF animals is characterized by low plasma renin activity and is aggravated by high-NaCl diet, suggesting a pathogenic role for sodium retention and hypervolemia probably secondary to renal insufficiency. Additionally, aortic stiffness was elevated in A-CRF animals as indicated by increased aortic pulse wave velocity. PMID:23515616

  2. Reduced BMPR2 expression induces GM-CSF translation and macrophage recruitment in humans and mice to exacerbate pulmonary hypertension

    PubMed Central

    Sawada, Hirofumi; Saito, Toshie; Nickel, Nils P.; Alastalo, Tero-Pekka; Glotzbach, Jason P.; Chan, Roshelle; Haghighat, Leila; Fuchs, Gabriele; Januszyk, Michael; Cao, Aiqin; Lai, Ying-Ju; Perez, Vinicio de Jesus; Kim, Yu-Mee; Wang, Lingli; Chen, Pin-I; Spiekerkoetter, Edda; Mitani, Yoshihide; Gurtner, Geoffrey C.; Sarnow, Peter

    2014-01-01

    Idiopathic pulmonary arterial hypertension (PAH [IPAH]) is an insidious and potentially fatal disease linked to a mutation or reduced expression of bone morphogenetic protein receptor 2 (BMPR2). Because intravascular inflammatory cells are recruited in IPAH pathogenesis, we hypothesized that reduced BMPR2 enhances production of the potent chemokine granulocyte macrophage colony-stimulating factor (GM-CSF) in response to an inflammatory perturbation. When human pulmonary artery (PA) endothelial cells deficient in BMPR2 were stimulated with tumor necrosis factor (TNF), a twofold increase in GM-CSF was observed and related to enhanced messenger RNA (mRNA) translation. The mechanism was associated with disruption of stress granule formation. Specifically, loss of BMPR2 induced prolonged phospho-p38 mitogen-activated protein kinase (MAPK) in response to TNF, and this increased GADD34–PP1 phosphatase activity, dephosphorylating eukaryotic translation initiation factor (eIF2?), and derepressing GM-CSF mRNA translation. Lungs from IPAH patients versus unused donor controls revealed heightened PA expression of GM-CSF co-distributing with increased TNF and expanded populations of hematopoietic and endothelial GM-CSF receptor ? (GM-CSFR?)–positive cells. Moreover, a 3-wk infusion of GM-CSF in mice increased hypoxia-induced PAH, in association with increased perivascular macrophages and muscularized distal arteries, whereas blockade of GM-CSF repressed these features. Thus, reduced BMPR2 can subvert a stress granule response, heighten GM-CSF mRNA translation, increase inflammatory cell recruitment, and exacerbate PAH. PMID:24446489

  3. Cardiac-specific overexpression of metallothionein attenuates myocardial remodeling and contractile dysfunction in l-NAME-induced experimental hypertension: Role of autophagy regulation.

    PubMed

    Yang, Lifang; Gao, Jian-Yuan; Ma, Jipeng; Xu, Xihui; Wang, Qiurong; Xiong, Lize; Yang, Jian; Ren, Jun

    2015-09-01

    Hypertension is an independent risk factor for heart disease and is responsible for the increased cardiac morbidity and mortality. Oxidative stress plays a key role in hypertensive heart diseases although the precise mechanism remains unclear. This study was designed to examine the effect of cardiac-specific overexpression of metallothionein, a cysteine-rich antioxidant, on myocardial contractile and intracellular Ca(2+) anomalies in N(G)-nitro-l-arginine methyl ester (l-NAME)-induced experimental hypertension and the mechanism involved with a focus on autophagy. Our results revealed that l-NAME treatment (14 days) led to hypertension and myocardial anomalies evidenced by interstitial fibrosis, cardiomyocyte hypertrophy, increased LV end systolic and diastolic diameters (LVESD and LVEDD) along with suppressed fractional shortening. l-NAME compromised cardiomyocyte contractile and intracellular Ca(2+) properties manifested as depressed peak shortening, maximal velocity of shortening/relengthening, electrically-stimulated rise in intracellular Ca(2+), elevated baseline and peak intracellular Ca(2+). These l-NAME-induced histological and mechanical changes were attenuated or reconciled by metallothionein. Protein levels of autophagy markers LC3B and p62 were decreased and increased, respectively. Autophagy signaling molecules AMPK, TSC2 and ULK1 were inactivated while those of mTOR and p70s6K were activated by l-NAME, the effects of which were ablated by metallothionein. Autophagy induction mimicked whereas autophagy inhibition nullified the beneficial effect of metallothionein against l-NAME. These findings suggested that metallothionein protects against l-NAME-induced myocardial anomalies possibly through restoration of autophagy. PMID:26068063

  4. Group B streptococcal phospholipid causes pulmonary hypertension

    NASA Astrophysics Data System (ADS)

    Curtis, Jerri; Kim, Geumsoo; Wehr, Nancy B.; Levine, Rodney L.

    2003-04-01

    Group B Streptococcus is the most common cause of bacterial infection in the newborn. Infection in many cases causes persistent pulmonary hypertension, which impairs gas exchange in the lung. We purified the bacterial components causing pulmonary hypertension and identified them as cardiolipin and phosphatidylglycerol. Synthetic cardiolipin or phosphatidylglycerol also induced pulmonary hypertension in lambs. The recognition that bacterial phospholipids may cause pulmonary hypertension in newborns with Group B streptococcal infection opens new avenues for therapeutic intervention.

  5. Chronic infusion of enalaprilat into hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension and cardiac hypertrophy by restoring neurotransmitters and cytokines

    SciTech Connect

    Kang, Yu-Ming, E-mail: ykang@mail.xjtu.edu.cn [Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061 (China); Zhang, Dong-Mei [Department of Physiology, Dalian Medical University, Dalian 116044 (China); Yu, Xiao-Jing; Yang, Qing; Qi, Jie; Su, Qing [Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061 (China); Suo, Yu-Ping [Department of Obstetrics and Gynecology, Shanxi Provincial People's Hospital, Taiyuan 030012 (China); Yue, Li-Ying [Department of Physiology and Pathophysiology, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University School of Medicine, Xi'an 710061 (China); Zhu, Guo-Qing [Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing 210029 (China); Qin, Da-Nian, E-mail: dnqin@stu.edu.cn [Department of Physiology, Shantou University Medical College, Shantou 515041 (China)

    2014-02-01

    The renin–angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. We hypothesized that inhibition of angiotensin-converting enzyme (ACE) in the hypothalamic paraventricular nucleus (PVN) attenuates angiotensin II (ANG II)-induced hypertension via restoring neurotransmitters and cytokines. Rats underwent subcutaneous infusions of ANG II or saline and bilateral PVN infusions of ACE inhibitor enalaprilat (ENL, 2.5 ?g/h) or vehicle for 4 weeks. ANG II infusion resulted in higher mean arterial pressure and cardiac hypertrophy as indicated by increased whole heart weight/body weight ratio, whole heart weight/tibia length ratio, left ventricular weight/tibia length ratio, and mRNA expressions of cardiac atrial natriuretic peptide and beta-myosin heavy chain. These ANG II-infused rats had higher PVN levels of glutamate, norepinephrine, tyrosine hydroxylase, pro-inflammatory cytokines (PICs) and the chemokine monocyte chemoattractant protein-1, and lower PVN levels of gamma-aminobutyric acid, interleukin (IL)-10 and the 67-kDa isoform of glutamate decarboxylase (GAD67), and higher plasma levels of PICs, norepinephrine and aldosterone, and lower plasma IL-10, and higher renal sympathetic nerve activity. However, PVN treatment with ENL attenuated these changes. PVN microinjection of ANG II induced increases in IL-1? and IL-6, and a decrease in IL-10 in the PVN, and pretreatment with angiotensin II type 1 receptor (AT1-R) antagonist losartan attenuated these changes. These findings suggest that ANG II infusion induces an imbalance between excitatory and inhibitory neurotransmitters and an imbalance between pro- and anti-inflammatory cytokines in the PVN, and PVN inhibition of the RAS restores neurotransmitters and cytokines in the PVN, thereby attenuating ANG II-induced hypertension and cardiac hypertrophy. - Highlights: • Chronic ANG II infusion results in sympathetic hyperactivity and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced hypertension and cardiac hypertrophy. • PVN inhibition of ACE attenuates ANG II-induced imbalance of PVN neurotransmitters. • PVN inhibition of ACE attenuates ANG II-induced imbalance of cytokines in the PVN. • PVN blockade of AT1-R attenuates ANG II-induced imbalance of cytokines in the PVN.

  6. Upregulation of Na+ and Ca2+ transporters in arterial smooth muscle from ouabain-induced hypertensive rats.

    PubMed

    Pulina, Maria V; Zulian, Alessandra; Berra-Romani, Roberto; Beskina, Olga; Mazzocco-Spezzia, Amparo; Baryshnikov, Sergey G; Papparella, Italia; Hamlyn, John M; Blaustein, Mordecai P; Golovina, Vera A

    2010-01-01

    Prolonged ouabain administration (25 microg kg(-1) day(-1) for 5 wk) induces "ouabain hypertension" (OH) in rats, but the molecular mechanisms by which ouabain elevates blood pressure are unknown. Here, we compared Ca(2+) signaling in mesenteric artery smooth muscle cells (ASMCs) from normotensive (NT) and OH rats. Resting cytosolic free Ca(2+) concentration ([Ca(2+)](cyt); measured with fura-2) and phenylephrine-induced Ca(2+) transients were augmented in freshly dissociated OH ASMCs. Immunoblots revealed that the expression of the ouabain-sensitive alpha(2)-subunit of Na(+) pumps, but not the predominant, ouabain-resistant alpha(1)-subunit, was increased (2.5-fold vs. NT ASMCs) as was Na(+)/Ca(2+) exchanger-1 (NCX1; 6-fold vs. NT) in OH arteries. Ca(2+) entry, activated by sarcoplasmic reticulum (SR) Ca(2+) store depletion with cyclopiazonic acid (SR Ca(2+)-ATPase inhibitor) or caffeine, was augmented in OH ASMCs. This reflected an augmented expression of 2.5-fold in OH ASMCs of C-type transient receptor potential TRPC1, an essential component of store-operated channels (SOCs); two other components of some SOCs were not expressed (TRPC4) or were not upregulated (TRPC5). Ba(2+) entry activated by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol [a measure of receptor-operated channel (ROC) activity] was much greater in OH than NT ASMCs. This correlated with a sixfold upregulation of TRPC6 protein, a ROC family member. Importantly, in primary cultured mesenteric ASMCs from normal rats, 72-h treatment with 100 nM ouabain significantly augmented NCX1 and TRPC6 protein expression and increased resting [Ca(2+)](cyt) and ROC activity. SOC activity was also increased. Silencer RNA knockdown of NCX1 markedly downregulated TRPC6 and eliminated the ouabain-induced augmentation; silencer RNA knockdown of TRPC6 did not affect NCX1 expression but greatly attenuated its upregulation by ouabain. Clearly, NCX1 and TRPC6 expression are interrelated. Thus, prolonged ouabain treatment upregulates the Na(+) pump alpha(2)-subunit-NCX1-TRPC6 (ROC) Ca(2+) signaling pathway in arterial myocytes in vitro as well as in vivo. This may explain the augmented myogenic responses and enhanced phenylephrine-induced vasoconstriction in OH arteries (83) as well as the high blood pressure in OH rats. PMID:19897708

  7. PARP-Inhibitor Treatment Prevents Hypertension Induced Cardiac Remodeling by Favorable Modulation of Heat Shock Proteins, Akt-1/GSK-3? and Several PKC Isoforms

    PubMed Central

    Deres, Laszlo; Bartha, Eva; Palfi, Anita; Eros, Krisztian; Riba, Adam; Lantos, Janos; Kalai, Tamas; Hideg, Kalman; Sumegi, Balazs; Gallyas, Ferenc; Toth, Kalman; Halmosi, Robert

    2014-01-01

    Spontaneously hypertensive rat (SHR) is a suitable model for studies of the complications of hypertension. It is known that activation of poly(ADP-ribose) polymerase enzyme (PARP) plays an important role in the development of postinfarction as well as long-term hypertension induced heart failure. In this study, we examined whether PARP-inhibitor (L-2286) treatment could prevent the development of hypertensive cardiopathy in SHRs. 6-week-old SHR animals were treated with L-2286 (SHR-L group) or placebo (SHR-C group) for 24 weeks. Wistar-Kyoto rats were used as aged-matched, normotensive controls (WKY group). Echocardiography was performed, brain-derived natriuretic peptide (BNP) activity and blood pressure were determined at the end of the study. We detected the extent of fibrotic areas. The amount of heat-shock proteins (Hsps) and the phosphorylation state of Akt-1Ser473, glycogen synthase kinase (GSK)-3?Ser9, forkhead transcription factor (FKHR)Ser256, mitogen activated protein kinases (MAPKs), and protein kinase C (PKC) isoenzymes were monitored. The elevated blood pressure in SHRs was not influenced by PARP-inhibitor treatment. Systolic left ventricular function and BNP activity did not differ among the three groups. L-2286 treatment decreased the marked left ventricular (LV) hypertrophy which was developed in SHRs. Interstitial collagen deposition was also decreased by L-2286 treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2Thr183-Tyr185, Akt-1Ser473, GSK-3?Ser9, FKHRSer256, and PKC ?Ser729 and the level of Hsp90 were increased, while the activity of PKC ?/?IIThr638/641, ?/?410/403 were mitigated by L-2286 administration. We could detect signs of LV hypertrophy without congestive heart failure in SHR groups. This alteration was prevented by PARP inhibition. Our results suggest that PARP-inhibitor treatment has protective effect already in the early stage of hypertensive myocardial remodeling. PMID:25014216

  8. PARP-inhibitor treatment prevents hypertension induced cardiac remodeling by favorable modulation of heat shock proteins, Akt-1/GSK-3? and several PKC isoforms.

    PubMed

    Deres, Laszlo; Bartha, Eva; Palfi, Anita; Eros, Krisztian; Riba, Adam; Lantos, Janos; Kalai, Tamas; Hideg, Kalman; Sumegi, Balazs; Gallyas, Ferenc; Toth, Kalman; Halmosi, Robert

    2014-01-01

    Spontaneously hypertensive rat (SHR) is a suitable model for studies of the complications of hypertension. It is known that activation of poly(ADP-ribose) polymerase enzyme (PARP) plays an important role in the development of postinfarction as well as long-term hypertension induced heart failure. In this study, we examined whether PARP-inhibitor (L-2286) treatment could prevent the development of hypertensive cardiopathy in SHRs. 6-week-old SHR animals were treated with L-2286 (SHR-L group) or placebo (SHR-C group) for 24 weeks. Wistar-Kyoto rats were used as aged-matched, normotensive controls (WKY group). Echocardiography was performed, brain-derived natriuretic peptide (BNP) activity and blood pressure were determined at the end of the study. We detected the extent of fibrotic areas. The amount of heat-shock proteins (Hsps) and the phosphorylation state of Akt-1(Ser473), glycogen synthase kinase (GSK)-3?(Ser9), forkhead transcription factor (FKHR)(Ser256), mitogen activated protein kinases (MAPKs), and protein kinase C (PKC) isoenzymes were monitored. The elevated blood pressure in SHRs was not influenced by PARP-inhibitor treatment. Systolic left ventricular function and BNP activity did not differ among the three groups. L-2286 treatment decreased the marked left ventricular (LV) hypertrophy which was developed in SHRs. Interstitial collagen deposition was also decreased by L-2286 treatment. The phosphorylation of extracellular signal-regulated kinase (ERK)1/2(Thr183-Tyr185), Akt-1(Ser473), GSK-3?(Ser9), FKHR(Ser256), and PKC ?(Ser729) and the level of Hsp90 were increased, while the activity of PKC ?/?II(Thr638/641), ?/?(410/403) were mitigated by L-2286 administration. We could detect signs of LV hypertrophy without congestive heart failure in SHR groups. This alteration was prevented by PARP inhibition. Our results suggest that PARP-inhibitor treatment has protective effect already in the early stage of hypertensive myocardial remodeling. PMID:25014216

  9. Different contributions of the endothelin ET(A) receptor to hypertension induced by acute or chronic inhibition of nitric oxide synthesis.

    PubMed

    Hashimoto, N; Kuro, T; Taira, S; Matsumura, Y

    1998-09-01

    The effects of FR139317((R)2-[(R)-2-[(S)-2-[[1-(hexahydro-1H-azepinyl)]carb onyl] amino-4-methyl-pentanoyl] amino-3-[3-(1-methyl-1H-indoyl)]propionyl]-amino-3-(2-pyridyl)prop ionic acid), an endothelin ET(A) receptor antagonist, on systemic and renal haemodynamic responses and excretory responses to chronic or acute nitric oxide (NO) synthase inhibition with NG-nitro-L-arginine (NOARG) have been examined. An intravenous bolus injection of FR139317 (10 mg kg(-1)) to chronic NO-deficient hypertensive rats (2.74 mM NOARG in drinking water for 4 weeks) elicited only a slight decrease in mean arterial pressure (MAP), to the same extent as seen in normotensive control rats. Injection of this drug induced no alteration of the renal haemodynamics of this chronic hypertensive model. Urine formation in control rats was significantly reduced by administration of FR139317. No significant decrease in urine formation was observed in the chronic NO-deficient rats. Acute intravenous injection of NOARG (5 mg kg(-1)) induced a gradual and significant increase in MAP, with a significant decrease in renal blood flow. A slight but insignificant diuretic effect was observed. In animals pretreated with FR139317 (10 mg kg(-1) i.v.) NOARG induced a significantly less potent increase in MAP, whereas similar renal haemodynamic responses to NOARG were observed. In contrast to the FR139317-untreated group, urine formation tended to decrease after administration of NOARG. These results suggest that endothelin, via the ET(A) receptor, contributes to the systemic pressor response to acute NO synthase inhibition, although renal vasoconstriction and functional changes induced by acute NO synthase inhibition are independent of ET(A) receptor-related effects. These results imply that action of endothelin via the ET(A) receptor is not involved in the maintenance of sustained hypertension induced by chronic NO synthase inhibition. PMID:9811167

  10. Postmenopausal Hypertension

    Microsoft Academic Search

    Licy L. Yanes; Jane F. Reckelhoff

    2011-01-01

    Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Hypertension is a major risk factor for cardiovascular disease. The mechanisms responsible for postmenopausal hypertension have not been completely elucidated. However, various mechanisms have been implicated to play a role. For example, there is evidence that changes in estrogen\\/androgen ratios favoring increases in androgens, activation of the

  11. Increased (Na+K+Cl) Cotransport in Rat Arterial Smooth Muscle in Deoxycorticosterone (DOCA)\\/Salt-Induced Hypertension

    Microsoft Academic Search

    R. A. Brown; A. R. Chipperfield; J. P. L. Davis; A. A. Harper

    1999-01-01

    The inhibition by loop diuretics of K efflux (tracer 86Rb) from the rat femoral arterial smooth muscle was measured in normotension and in DOCA-salt hypertension. The sensitivity sequence (bumetanide > piretanide > furosemide) was the characteristic pharmacological profile of (Na+K+Cl) cotransport. In hypertension, cotransport activity was 46% greater than in normotension and the sensitivity to loop diuretics was threefold less.

  12. Salt-Sensitive Hypertension Induced by Decoy of Transcription Factor HIF-1? in the Renal Medulla

    PubMed Central

    Li, Ningjun; Li, Chen; Yi, Fan; Xia, Min; Li, Pin-Lan

    2009-01-01

    Hypoxia inducible factor-1? (HIF-1?), a transcription factor, is abundantly expressed in the renal medulla and regulates many oxygen-sensitive genes such as nitric oxide synthase (NOS), cyclooxygenase-2 and heme oxygenase-1 (HO-1). Given the important roles of these genes in the control of arterial pressure, the present study was to test the hypothesis that HIF-1?-mediated gene activation serves as an antihypertensive pathway by regulating renal medullary function and sodium excretion. HIF-1? decoy oligodeoxynucleotides (ODN) or scrambled ODN were transfected into the renal medulla in uninephretomized Sprague Dawley rats. Two weeks after ODN transfection, the HIF-1? binding activities were significantly inhibited by 45%, and high salt-induced increases of NOS2 and HO-1 transcriptions were also inhibited by 70% and 61% in the renal medulla from decoy rats. The natriuretic responses and increases of renal medullary blood flow (MBF) responding to the elevations of renal perfusion pressure were significantly blunted by 50% and 37% in decoy rats. Intravenously acute sodium loading increased MBF and urinary sodium excretion, which was remarkably attenuated in decoy rats. In decoy rats, high salt intake caused a greater positive sodium balance. Consequently, arterial pressure was remarkably increased (from 118 ± 1.9 to 154 ± 6.3 mmHg) in decoy rats, but not in control rats, when the rats were challenged with a high salt diet. There was no blood pressure change in decoy rats that were maintained in normal salt diet. In conclusion, HIF-1?-mediated gene activation importantly participates in the regulation of renal medullary function and long-term arterial blood pressure. PMID:18356541

  13. The Effect of Umbilical Cord Blood Derived Mesenchymal Stem Cells in Monocrotaline-induced Pulmonary Artery Hypertension Rats.

    PubMed

    Lee, Hyeryon; Lee, Jae Chul; Kwon, Jung Hyun; Kim, Kwan Chang; Cho, Min-Sun; Yang, Yoon Sun; Oh, Wonil; Choi, Soo Jin; Seo, Eun-Seok; Lee, Sang-Joon; Wang, Tae Jun; Hong, Young Mi

    2015-05-01

    Pulmonary arterial hypertension (PAH) causes right ventricular failure due to a gradual increase in pulmonary vascular resistance. The purposes of this study were to confirm the engraftment of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) placed in the correct place in the lung and research on changes of hemodynamics, pulmonary pathology, immunomodulation and several gene expressions in monocrotaline (MCT)-induced PAH rat models after hUCB-MSCs transfusion. The rats were grouped as follows: the control (C) group; the M group (MCT 60 mg/kg); the U group (hUCB-MSCs transfusion). They received transfusions via the external jugular vein a week after MCT injection. The mean right ventricular pressure (RVP) was significantly reduced in the U group after the 2 week. The indicators of RV hypertrophy were significantly reduced in the U group at week 4. Reduced medial wall thickness in the pulmonary arteriole was noted in the U group at week 4. Reduced number of intra-acinar muscular pulmonary arteries was observed in the U group after 2 week. Protein expressions such as endothelin (ET)-1, endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 significantly decreased at week 4. The decreased levels of ERA, eNOS and MMP-2 immunoreactivity were noted by immnohistochemical staining. After hUCB-MSCs were administered, there were the improvement of RVH and mean RVP. Reductions in several protein expressions and immunomodulation were also detected. It is suggested that hUCB-MSCs may be a promising therapeutic option for PAH. PMID:25931788

  14. Reduction of endoplasmic reticulum stress by 4-phenylbutyric acid prevents the development of hypoxia-induced pulmonary arterial hypertension.

    PubMed

    Koyama, Masayuki; Furuhashi, Masato; Ishimura, Shutaro; Mita, Tomohiro; Fuseya, Takahiro; Okazaki, Yusuke; Yoshida, Hideaki; Tsuchihashi, Kazufumi; Miura, Tetsuji

    2014-05-01

    Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction and vascular remodeling of the pulmonary artery (PA). Recently, endoplasmic reticulum (ER) stress and inappropriate adaptation through the unfolded protein response (UPR) have been disclosed in various types of diseases. Here we examined whether ER stress is involved in the pathogenesis of PAH. Four weeks of chronic normobaric hypoxia increased right ventricular (RV) systolic pressure by 63% compared with that in normoxic controls and induced RV hypertrophy and medial thickening of the PA in C57BL/6J mice. Treatment with 4-phenylbutyric acid (4-PBA), a chemical chaperone, significantly reduced RV systolic pressure by 30%, attenuated RV hypertrophy and PA muscularization, and increased total running distance in a treadmill test by 70% in hypoxic mice. The beneficial effects of 4-PBA were associated with suppressed expression of inflammatory cytokines and ER stress markers, including Grp78 and Grp94 in the activating transcription factor-6 branch, sXbp1 and Pdi in the inositol-requiring enzyme-1 branch and Atf4 in the PKR-like ER kinase branch, and reduced phosphorylation of c-Jun NH2-terminal kinase and eukaryotic translation initiation factor-2? in the lung. The pattern of changes in ER stress and inflammatory markers by 4-PBA in the lung of the PAH model was reproduced in PA smooth muscle cells by chronic stimulation of platelet-derived growth factor-BB or hypoxia. Furthermore, knockdown of each UPR branch sensor activated other branches and promoted proliferation of PA smooth muscle cells. The findings indicate that activation of all branches of the UPR and accompanying inflammation play a major role in the pathogenesis of PAH, and that chemical chaperones are potentially therapeutic agents for PAH. PMID:24610918

  15. Tranexamic Acid Diminishes Laser-Induced Melanogenesis

    PubMed Central

    Kim, Myoung Shin; Bang, Seung Hyun; Kim, Jeong-Hwan; Shin, Hong-Ju; Choi, Jee-Ho

    2015-01-01

    Background The treatment of post-inflammatory hyperpigmentation (PIH) remains challenging. Tranexamic acid, a well-known anti-fibrinolytic drug, has recently demonstrated a curative effect towards melasma and ultraviolet-induced PIH in Asian countries. However, the precise mechanism of its inhibitory effect on melanogenesis is not fully understood. Objective In order to clarify the inhibitory effect of tranexamic acid on PIH, we investigated its effects on mouse melanocytes (i.e., melan-a cells) and human melanocytes. Methods Melan-a cells and human melanocytes were cultured with fractional CO2 laser-treated keratinocyte-conditioned media. Melanin content and tyrosinase activity were evaluated in cells treated with or without tranexamic acid. Protein levels of tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 were evaluated in melan-a cells. Signaling pathway molecules involved in melanogenesis in melanoma cells were also investigated. Results Tranexamic acid-treated melanocytes exhibited reduced melanin content and tyrosinase activity. Tranexamic acid also decreased tyrosinase, TRP-1, and TRP-2 protein levels. This inhibitory effect on melanogenesis was considered to be involved in extracellular signal-regulated kinase signaling pathways and subsequently microphthalmia-associated transcription factor degradation. Conclusion Tranexamic acid may be an attractive candidate for the treatment of PIH.

  16. Impact of tannic acid on blood pressure, oxidative stress and urinary parameters in L-NNA-induced hypertensive rats.

    PubMed

    Turgut Co?an, Didem; Saydam, Faruk; Özbayer, Cansu; Do?aner, Fulya; Soyocak, Ahu; Güne?, Hasan Veysi; De?irmenci, ?rfan; Kurt, Hülyam; Üstüner, Mehmet Cengiz; Bal, Cengiz

    2015-01-01

    Hypertension is a major health problem with increasing prevalence around the world. Tannic acid is water-soluble polyphenol that is present in tea, green tea, coffee, red wine, nuts, fruits and many plant foods. It has been reported to serve as an antioxidant or a pro-oxidant depending on the type of cells and its concentration. The purpose of our study was to evaluate the effect of tannic acid on systolic blood pressure, oxidative stress and some urinary parameters in the rat model of essential hypertension. Blood pressures of all rats were measured using the tail-cuff method. The nitric oxide synthase inhibitor N (omega)-nitro-L-arginine was administered orally at a dose of 0.5 g/l/day for 15 days to rats in order to create an animal model of hypertension. Tannic acid was intraperitoneally injected at a dose of 50 mg/kg for 15 days. Superoxide dismutase, catalase activity and the concentration of malondialdehyde (MDA) were determined in blood plasma and homogenates of heart, liver and kidney. In order to evaluate renal functions, urine pH, urine volume, urine creatine, uric acid, and urea nitrogen values were measured. Compared with the hypertension group, a decrease in MDA concentrations of heart tissue (p < 0.01), urea nitrogen values (p < 0.01) and urine volumes (p < 0.001) were established in hypertension + tannic acid group. There was also a decrease in blood pressure values (20th and 30th days) of this group, but there was no a statistical difference according to hypertension group. The findings of our research show the effect of tannic acid in lowering blood pressure in hypertensive rats. PMID:24306272

  17. Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression

    PubMed Central

    Trudu, Matteo; Janas, Sylvie; Lanzani, Chiara; Debaix, Huguette; Schaeffer, Céline; Ikehata, Masami; Citterio, Lorena; Demaretz, Sylvie; Trevisani, Francesco; Ristagno, Giuseppe; Glaudemans, Bob; Laghmani, Kamel; Dell’Antonio, Giacomo; Loffing, Johannes; Rastaldi, Maria P.; Manunta, Paolo

    2013-01-01

    Elevated blood pressure (BP) and chronic kidney disease (CKD) are complex traits representing major global health problems1,2. Multiple genome-wide association studies (GWAS) identified common variants giving independent susceptibility for CKD and hypertension in the promoter of the UMOD gene3-9, encoding uromodulin, the major protein secreted in the normal urine. Despite compelling genetic evidence, the underlying biological mechanism is not understood. Here, we demonstrate that UMOD risk variants directly increase UMOD expression in vitro and in vivo. We modeled this effect in transgenic mice and showed that uromodulin overexpression leads to salt-sensitive hypertension and to age-dependent renal lesions that are similarly observed in elderly subjects homozygous for UMOD risk variants. We demonstrate that the link between uromodulin and hypertension is caused by activation of the renal sodium co-transporter NKCC2. This very mechanism is relevant in humans, as pharmacological inhibition of NKCC2 is more effective in lowering BP in hypertensive patients homozygous for UMOD risk variants. Our findings establish a link between the genetic susceptibility to hypertension and CKD, the control of uromodulin expression and its role in a salt-reabsorbing tubular segment of the kidney. These data point to uromodulin as a novel therapeutic target to lower BP and preserve renal function. PMID:24185693

  18. The effect of hydroalcoholic extract from the leaves of Moringa peregrina (Forssk.) Fiori. on blood pressure and oxidative status in dexamethasone-induced hypertensive rats

    PubMed Central

    Safaeian, Leila; Asghari, Gholamreza; Javanmard, Shaghayegh Haghjoo; Heidarinejad, Arman

    2015-01-01

    Background: Moringa peregrina (Forssk.) Fiori. is a tropical tree growing in southeast of Iran. All parts of this plant have nutritional uses and pharmacological activities. The present study was designed to evaluate the effect of hydroalcoholic extract from the leaves of M. peregrina in dexamethasone (Dex)-induced hypertension in rats. Materials and Methods: Male Wistar rats received Dex (30 ?g/kg, subcutaneously; s.c.) or saline (as vehicle, 1 ml/kg, s.c.) for 14 days. In a prevention study, the rats received M. peregrina extract (100, 200 and 400 mg/kg, orally) for 4 days, followed by Dex for 14 days. In a reversal study, the animals received M. peregrina extract orally from day 8 to 14. The systolic blood pressure (SBP) was measured using tail-cuff method. The hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) were assessed in plasma samples. Results: Dex significantly increased the SBP and the plasma H2O2 and decreased the plasma FRAP value (P < 0.001). M. peregrina extract at a dose of 400 mg/kg prevented (P < 0.01) but did not reverse Dex-induced hypertension in rats. It also dose-dependently reduced the plasma H2O2 concentration and improved the FRAP value upon Dex administration. Conclusions: The findings of the present study indicated the antioxidant and partially antihypertensive effects of the hydroalcoholic extract from the leaves of M. peregrina in Dex-induced hypertension. Further experiments on other fractions of the leaves and also other parts of this plant are suggested for better evaluation of its antihypertensive effect and finding its mechanisms of action. PMID:26015927

  19. Over-Expression of Copper/Zinc Superoxide Dismutase in the Median Preoptic Nucleus Attenuates Chronic Angiotensin II-Induced Hypertension in the Rat

    PubMed Central

    Collister, John P.; Bellrichard, Mitch; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C.

    2014-01-01

    The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·?) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·? in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2·? in the MnPO contributes to the development of chronic AngII-dependent hypertension. PMID:25474089

  20. Over-expression of copper/zinc superoxide dismutase in the median preoptic nucleus attenuates chronic angiotensin II-induced hypertension in the rat.

    PubMed

    Collister, John P; Bellrichard, Mitch; Drebes, Donna; Nahey, David; Tian, Jun; Zimmerman, Matthew C

    2014-01-01

    The brain senses circulating levels of angiotensin II (AngII) via circumventricular organs, such as the subfornical organ (SFO), and is thought to adjust sympathetic nervous system output accordingly via this neuro-hormonal communication. However, the cellular signaling mechanisms involved in these communications remain to be fully understood. Previous lesion studies of either the SFO, or the downstream median preoptic nucleus (MnPO) have shown a diminution of the hypertensive effects of chronic AngII, without providing a clear explanation as to the intracellular signaling pathway(s) involved. Additional studies have reported that over-expressing copper/zinc superoxide dismutase (CuZnSOD), an intracellular superoxide (O2·-) scavenging enzyme, in the SFO attenuates chronic AngII-induced hypertension. Herein, we tested the hypothesis that overproduction of O2·- in the MnPO is an underlying mechanism in the long-term hypertensive effects of chronic AngII. Adenoviral vectors encoding human CuZnSOD (AdCuZnSOD) or control vector (AdEmpty) were injected directly into the MnPO of rats implanted with aortic telemetric transmitters for recording of arterial pressure. After a 3 day control period of saline infusion, rats were intravenously infused with AngII (10 ng/kg/min) for ten days. Rats over-expressing CuZnSOD (n = 7) in the MnPO had a blood pressure increase of only 6 ± 2 mmHg after ten days of AngII infusion while blood pressure increased 21 ± 4 mmHg in AdEmpty-infected rats (n = 9). These results support the hypothesis that production of O2·- in the MnPO contributes to the development of chronic AngII-dependent hypertension. PMID:25474089

  1. Persistent perioperative tachycardia and hypertension diagnosed as thyroid storm induced by a hydatidiform mole: a case report

    PubMed Central

    Hwang, Wonjung; Im, Daehwan

    2014-01-01

    Thyroid storm is a critical complication of molar pregnancy. However, early diagnosis of it is difficult because it is a rare complication and usually presents nonspecific findings. In this case report, we present a woman with molar pregnancy who had persistent tachycardia and hypertension. She was diagnosed initially with preeclampsia and sepsis as complications of molar pregnancy. During dilation and curettage under general anesthesia with sevoflurane and remifentanil, tachycardia and hypertension remained even with continuous infusion of labetalol. The patient was subsequently diagnosed with thyroid storm associated with molar pregnancy. She was restored to a clinically euthyroid state 1 day after the operation, and her thyroid function test and ?-hCG values were normal 3 months later. The anesthesiologists should bear in mind the possibility of thyroid storm in patients with molar pregnancies who show persistent tachycardia and hypertension. PMID:25302097

  2. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.

    PubMed

    Konno, Takashi; Uchibori, Takehiro; Nagai, Akihiko; Kogi, Kentaro; Nakahata, Norimichi

    2005-08-22

    The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production. PMID:16023100

  3. Pre-eclampsia but not pregnancy-induced hypertension is a risk factor for diabetic nephropathy in type 1 diabetic women

    Microsoft Academic Search

    D. Gordin; V. Hiilesmaa; J. Fagerudd; M. Rönnback; C. Forsblom; R. Kaaja; K. Teramo; P.-H. Groop

    2007-01-01

    Aims\\/hypothesis  Our aim was to study whether pre-eclampsia and pregnancy-induced hypertension are predictors of diabetic nephropathy in type\\u000a 1 diabetic women.\\u000a \\u000a \\u000a \\u000a Materials and methods  A total of 203 type 1 diabetic women, who were pregnant between 1988 and 1996 and followed at the Department of Obstetrics\\u000a and Gynaecology in Helsinki, were re-assessed after an average of 11 years within the nationwide, multi-centre Finnish

  4. 2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K + channel opening through adenosine A 2A receptor in rabbits

    Microsoft Academic Search

    Takashi Konno; Takehiro Uchibori; Akihiko Nagai; Kentaro Kogi; Norimichi Nakahata

    2005-01-01

    The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 ?l)-induced ocular hypertension (Emax: 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist

  5. Role of iNOS in the vasodilator responses induced by L-arginine in the middle cerebral artery from normotensive and hypertensive rats

    PubMed Central

    Briones, Ana M; Alonso, María J; Marín, Jesús; Salaices, Mercedes

    1999-01-01

    The substrate of nitric oxide synthase (NOS), L-arginine (L-Arg, 0.01??M?1?mM), induced endothelium-independent relaxations in segments of middle cerebral arteries (MCAs) from normotensive Wistar-Kyoto (WKY) and hypertensive rats (SHR) precontracted with prostaglandin F2? (PGF2?). These relaxations were higher in SHR than WKY arteries.L-NG-nitroarginine methyl ester (L-NAME) and 2-amine-5,6-dihydro-6-methyl-4H-1,3-tiazine (AMT), unspecific and inducible NOS (iNOS) inhibitors, respectively, reduced those relaxations, specially in SHR.Four- and seven-hours incubation with dexamethasone reduced the relaxations in MCAs from WKY and SHR, respectively.Polymyxin B and calphostin C, protein kinase C (PKC) inhibitors, reduced the L-Arg-induced relaxation.Lipopolysaccharide (LPS, 7?h incubation) unaltered and inhibited these relaxations in WKY and SHR segments, respectively. LPS antagonized the effect polymyxin B in WKY and potentiated L-Arg-induced relaxations in SHR in the presence of polymyxin B.The contraction induced by PGF2? was greater in SHR than WKY arteries. This contraction was potentiated by dexamethasone and polymyxin B although the effect of polymyxin B was higher in SHR segments. LPS reduced that contraction and antagonized dexamethasone- and polymyxin B-induced potentiation, these effects being greater in arteries from SHR.These results suggest that in MCAs: (1) the induction of iNOS participates in the L-Arg relaxation and modulates the contraction to PGF2?; (2) that induction is partially mediated by a PKC-dependent mechanism; and (3) the involvement of iNOS in such responses is greater in the hypertensive strain. PMID:10051127

  6. Attenuation of Monocrotaline-Induced Pulmonary Hypertension by Luminal Adeno-Associated Virus Serotype 9 Gene Transfer of Prostacyclin Synthase

    PubMed Central

    Gubrij, Igor B.; Martin, Sara Rebecca; Pangle, Amanda K.; Kurten, Richard

    2014-01-01

    Abstract Idiopathic pulmonary arterial hypertension (iPAH) is associated with high morbidity and mortality. We evaluated whether luminal delivery of the human prostacyclin synthase (hPGIS) cDNA with adeno-associated virus (AAV) vectors could attenuate PAH. AAV serotype 5 (AAV5) and AAV9 vectors containing the hPGIS cDNA under the control of a cytomegalovirus-enhanced chicken ?-actin (CB) promoter or vehicle (saline) were instilled into lungs of rats. Two days later, rats were injected with monocrotaline (MCT, 60?mg/kg) or saline. Biochemical, hemodynamic, and morphologic assessments were performed when the rats developed symptoms (3–4 weeks) or at 6 weeks. Luminal (airway) administration of AAV5 and AAV9CBhPGIS vectors (MCT-AAV5 and MCT-AAV9 rats) significantly increased plasma levels of 6-keto-PGF1? as compared with MCT-controls, and closely resembled levels measured in rats not treated with MCT (saline–saline). Right ventricular (RV)/left ventricular (LV)+septum (S) ratios and RV systolic pressure (RVSP) were greater in MCT-control rats than in saline–saline rats, whereas the ratios and RVSP in MCT-AAV5CBhPGIS and MCT-AAV9CBhPGIS rats were similar to saline–saline rats. Thickening of the muscular media of small pulmonary arteries of MCT-control rats was detected in histological sections, whereas the thickness of the muscular media in MCT-AAV5CBhPGIS and MCT-AAV9CBhPGIS rats was similar to saline–saline controls. In experiments with different promoters, a trend toward increased levels of PGF1? expression was detected in lung homogenates, but not plasma, of MCT-treated rats transduced with an AAV9-hPGIS vector containing a CB promoter. This correlated with significant reductions in the RV/LV+S ratio and RVSP in MCT-AAV9CBhPGIS rats that resembled levels in saline–saline rats. No changes in levels of PGF1?, RV/LV+S, or RVSP were detected in rats transduced with AAV9-hPGIS vectors containing a modified CB promoter (CB7) or a distal epithelial cell-specific promoter (CC10). Thus, AAV9CBhPGIS vectors prevented development of MCT-induced PAH and associated pulmonary vascular remodeling. PMID:24512101

  7. 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

  8. The effect of hydro-alcoholic celery (Apiumgraveolens) leaf extract on cardiovascular parameters and lipid profile in animal model of hypertension induced by fructose

    PubMed Central

    Dianat, Mahin; Veisi, Ali; Ahangarpour, Akram; Fathi Moghaddam, Hadi

    2015-01-01

    Objectives: Hypertension is one of the most common diseases of the modern era. This study evaluates the effect of hydro-alcoholic celery leaf extract onsystolic blood pressure (SBP), heart rate (HR) and lipid profile in animals’ model of hypertension induced by fructose. Materials and Methods: Sprague Dawley rats were divided into five groups: 1) control group (free access to tap drinking water), 2) group receiving 200mg/kg celery leaf extract, 3) group receiving fructose 10%, and 4,5) receiving fructose and 100mg/kg or 200mg/kg of extract (n=8). In all groups, before and during the test period, SBP and HR were measured by Power lab system. Lipid profiles were determined by auto analysis. Repeated measurement and one way ANOVA were used for data analysis. P<0.05 was considered statistically significant. Results: The SBP in the fructose group significantly increased compared to control group (P<0.01). SBP, in groups receiving fructose+100mg/kg extract, fructose and receiving 200mg/kg extract, and receiving 200mg/kg of extract, compared to fructose group significantly decreased. Heart rate in any of these groups showed no significant difference. Cholesterol, triglyceride, LDL and VLDL in the fructose group significantly increased; however, these effects significantly decreased in the recipient extract groups. HDL levels in the fructose group showed no difference while in the groups receiving the extract they significantly increased. Conclusions: Celery leaf extract reduces SBP, cholesterol, triglyceride, LDL and VLDL in animal model of fructose-induced hypertension. In conclusion, celery leaf extract with its blood pressure and lipid lowering effects, can be considered as an antihypertensive agent in chronic treatment of elevated SBP.

  9. Role of STAT3 in Angiotensin II-Induced Hypertension and Cardiac Remodeling Revealed by Mice Lacking STAT3 Serine 727 Phosphorylation

    PubMed Central

    Zouein, Fouad A.; Zgheib, Carlos; Hamza, Shereen; Fuseler, John W.; Hall, John E.; Soljancic, Andrea; Lopez-Ruiz, Arnaldo; Kurdi, Mazen; Booz, George W.

    2013-01-01

    STAT3 is involved in protection of the heart provided by ischemic preconditioning. However, the role of this transcription factor in the heart in chronic stresses such as hypertension has not been defined. We assessed whether STAT3 is important in hypertension-induced cardiac remodeling using mice with reduced STAT3 activity due to a S727A mutation (SA/SA). Wild type (WT) and SA/SA mice received angiotensin (ANG) II or saline for 17 days. ANG II increased mean arterial and systolic pressure in SA/SA and WT mice, but cardiac levels of cytokines associated with heart failure were increased less in SA/SA mice. Unlike WT mice, hearts of SA/SA mice showed signs of developing systolic dysfunction as evidenced by reduction in ejection fraction and fractional shortening. In the left ventricle of both WT and SA/SA mice, ANG II induced fibrosis. However, fibrosis in SA/SA mice appeared more extensive and was associated with loss of myocytes. Cardiac hypertrophy as indexed by heart to body weight ratio and left ventricular anterior wall dimension during diastole was greater in WT mice. In WT+ANG II mice there was an increase in the mass of individual myofibrils. In contrast, cardiac myocytes of SA/SA+ANG II mice showed a loss in myofibrils and myofibrillar mass density was decreased during ANG II infusion. Our findings reveal that STAT3 transcriptional activity is important for normal cardiac myocyte myofibril morphology. Loss of STAT3 may impair cardiac function in the hypertensive heart due to defective myofibrillar structure and remodeling that may lead to heart failure. PMID:23364341

  10. Augmented Endothelial-Specific L-Arginine Transport Blunts the Contribution of the Sympathetic Nervous System to Obesity Induced Hypertension in Mice

    PubMed Central

    Rajapakse, Niwanthi W.; Karim, Florian; Evans, Roger G.

    2015-01-01

    Augmenting endothelial specific transport of the nitric oxide precursor L-arginine via cationic amino acid transporter-1 (CAT1) can prevent obesity related hypertension. We tested the hypotheses that CAT1 overexpression prevents obesity-induced hypertension by buffering the influence of the sympathetic nervous system (SNS) on the maintenance of arterial pressure and by buffering pressor responses to stress. Wild type (WT; n=13) and CAT1 overexpressing mice (CAT+; n=13) were fed a normal or a high fat diet for 20 weeks. Mice fed a high fat diet were returned to the control diet before experiments commenced. Baseline mean arterial pressure (MAP) and effects of restraint-, shaker- and almond feeding-stress and ganglionic blockade (pentolinium; 5 mg/kg; i.p.) on MAP were determined in conscious mice. Fat feeding increased body weight to a similar extent in WT and CAT+ but MAP was greater only in WT compared to appropriate controls (by 29%). The depressor response to pentolinium was 65% greater in obese WT than lean WT (P < 0.001), but was similar in obese and lean CAT+ (P = 0.65). In lean WT and CAT+, pressor responses to shaker and feeding stress, but not restraint stress, were less in the latter genotype compared to the former (P ? 0.001). Pressor responses to shaker and feeding stress were less in obese WT than lean WT (P ? 0.001), but similar in obese and lean CAT+. The increase in MAP in response to restraint stress was less in obese WT (22 ± 2%), but greater in obese CAT+ (37 ± 2%), when compared to respective lean WT (31 ± 3%) and lean CAT+ controls (27 ± 2%; P ? 0.02). We conclude that CAT1 overexpression prevents obesity-induced hypertension by reducing the influence of the SNS on the maintenance of arterial pressure but not by buffering pressor responses to stress. PMID:26186712

  11. Role of the Renin-Angiotensin System, Renal Sympathetic Nerve System, and Oxidative Stress in Chronic Foot Shock-Induced Hypertension in Rats

    PubMed Central

    Dong, Tao; Chen, Jing-Wei; Tian, Li-Li; Wang, Lin-Hui; Jiang, Ren-Di; Zhang, Zhe; Xu, Jian-Bing; Zhao, Xiao-Dong; Zhu, Wei; Wang, Guo-Qing; Sun, Wan-Ping; Zhang, Guo-Xing

    2015-01-01

    Objective: The renin-angiotensin system (RAS) and renal sympathetic nerve system (RSNS) are involved in the development of hypertension. The present study is designed to explore the possible roles of the RAS and the RSNS in foot shock-induced hypertension. Methods: Male Sprague-Dawley rats were divided into six groups: control, foot shock, RSNS denervation, denervation plus foot shock, Captopril (angiotensin I converting enzyme inhibitor, ACE inhibitor) plus foot shock, and Tempol (superoxide dismutase mimetic) plus foot shock. Rats received foot shock for 14 days. We measured the quantity of thiobarbituric acid reactive substances (TBARS), corticosterone, renin, and angiotensin II (Ang II) in plasma, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and renal noradrenaline content. RAS component mRNA and protein levels were quantified in the cerebral cortex and hypothalamus. Results: The two week foot shock treatment significantly increased systolic blood pressure, which was accompanied by an increase in angiotensinogen, renin, ACE1, and AT1a mRNA and protein expression in the cerebral cortex and hypothalamus, an increase of the plasma concentrations of renin, Ang II, corticosterone, and TBARS, as well as a decrease in plasma SOD and GSH-Px activities. Systolic blood pressure increase was suppressed by denervation of the RSNS or treatment with Captopril or Tempol. Interestingly, denervation or Tempol treatment both decreased main RAS components not only in the circulatory system, but also in the central nervous system. In addition, decreased antioxidant levels and increased TBARS and corticosterone levels were also partially restored by denervation or treatment with Tempol or Captopril. Conclusions: RAS, RSNS and oxidative stress reciprocally potentiate to play important roles in the development of foot shock-induced hypertension. PMID:25999788

  12. Calorie restriction improves cognitive decline via up-regulation of brain-derived neurotrophic factor: tropomyosin-related kinase B in hippocampus ofobesity-induced hypertensive rats.

    PubMed

    Kishi, Takuya; Hirooka, Yoshitaka; Nagayama, Tomomi; Isegawa, Kengo; Katsuki, Masato; Takesue, Ko; Sunagawa, Kenji

    2015-01-01

    In metabolic syndrome (MetS), previous studies have suggested that cognitive decline is worsened. Among the factors associated with cognition, decreased brain-derived neurotrophic factor (BDNF) in the hippocampus causes cognitive decline. We previously reported that exercise training with calorie restriction yielded protection against cognitive decline via BDNF in the hippocampus of hypertensive rats. The aim of the present study was to determine whether or not calorie restriction results in protection against cognitive decline via BDNF and its receptor tropomyosin-related kinase B (TrkB) in the hippocampus of MetS model rats. We divided dietary-induced obesity-prone and hypertensive rats (OP), as metabolic syndrome model rats, into three groups, fed with a high fat diet (HF), treated with calorie restriction (CR) plus vehicle, and treated with CR and ANA-12 (a TrkB antagonist) (CR+A). After treatment for 28 days, body weight, insulin, fasting blood glucose, adiponectin, systolic blood pressure, and oxidative stress in the hippocampus were significantly lower, and BDNF expression in the hippocampus was significantly higher in CR and CR+A than in HF. Cognitive performance determined by the Morris water maze test was significantly higher in CR than in HF, whereas the benefit was attenuated in CR+A. In conclusion, calorie restriction protects against cognitive decline via up-regulation of BDNF/TrkB through an antioxidant effect in the hippocampus of dietary-induced obesity rats. PMID:25503654

  13. Grape seed proanthocyanidins prevent DOCA-salt hypertension-induced renal injury and its mechanisms in rats.

    PubMed

    Lan, Chao-Zong; Ding, Ling; Su, Yi-Lin; Guo, Kun; Wang, Li; Kan, Hong-Wei; Ou, Yu-Rong; Gao, Shan

    2015-07-01

    Renal dysfunction is one of the major effects of DOCA (deoxycorticosterone acetate)-salt hypertension and there is an increasing amount of evidence that oxidative stress damages the function of the kidney. Grape seed proanthocyanidins (GSPE) have been reported to be potent anti-oxidants and free radical scavengers. The present study sought to investigate the ability of GSPE to prevent renal injury in DOCA-salt hypertensive rats and to explore the molecular mechanisms underlying its protective effects. A total of 54 Sprague Dawley (SD) rats were randomly divided into 7 groups: Sham group (n = 7), UnX-sham group (n = 8), DOCA-salt group (n = 8), GSPE150 group (150 mg kg(-1), n = 7), GSPE240 group (240 mg kg(-1), n = 8), GSPE384 group (384 mg kg(-1), n = 8) and ALM (amlodipine besylate tablets) group (5 mg kg(-1), n = 8), and treated for 4 weeks. Compared to sham group rats, renal injury was observed in DOCA-salt hypertensive group rats as the urine protein, KW/BW (kidney weight/body weight), degree of renal fibrosis, renal MDA (malondialdehyde) and Hyp (hydroxyproline) contents significantly increased (P < 0.01). Moreover, SOD (Superoxide Dismutase) activities decreased in the model group (P < 0.01). In contrast, DOCA-salt hypertensive rats treated with different dose of GSPE or ALM showed a significant improvement of renal injury with decreased urine protein, KW/BW, degree of renal fibrosis, renal total MDA and Hyp contents compared to the untreated group. In addition, SOD activities increased in the treatment group. Since the experimental modeling time was short, kidney damage occurs to a lesser extent. BUN (Blood Urea Nitrogen), Scr (Serum Creatinine) and UA (Uric Acid) contents did not appear significantly changed in all groups. Finally, the activation of JNK and p38 kinases in the kidney was suppressed in rats treated with GSPEs or ALM compared to the untreated group, suggesting that the inhibition of these kinase pathways by GSPE contributes to the improvement of renal function. Taking these results together, we conclude that the anti-hypertensive and anti-oxidative stress beneficial effects of GSPE on renal injury in rats with DOCA-salt hypertension occur via the attenuation of JNK and p38 activity. PMID:26011796

  14. Impaired ?-adrenoceptor-induced relaxation in small mesenteric arteries from DOCA-salt hypertensive rats is due to reduced KCa channel activity

    PubMed Central

    Matsumoto, Takayuki; Szasz, Theodora; Tostes, Rita C.; Webb, R. Clinton

    2012-01-01

    ?-Adrenoceptor (?-AR)-mediated relaxation plays an important role in the regulation of vascular tone. ?-AR-mediated vascular relaxation is reduced in various disease states and aging. We hypothesized that ?-AR-mediated vasodilatation is impaired in DOCA-salt hypertension due to alterations in the cAMP pathway. ?-AR-mediated relaxation was determined in small mesenteric arteries from DOCA-salt hypertensive and control uninephrectomized (Uni) rats. To exclude nitric oxide (NO) and cyclooxygenase (COX) pathways, relaxation responses were determined in the presence of L-NNA and indomethacin, NO synthase inhibitor and COX inhibitors, respectively. Isoprenaline (ISO)-induced relaxation was reduced in arteries from DOCA-salt compared to Uni rats. Protein kinase A (PKA) inhibitors (H89 or Rp-cAMPS) or adenylyl cyclase inhibitor (SQ22536) did not abolish the difference in ISO-induced relaxation between the groups. Forskolin (adenylyl cyclase activator)-induced relaxation was similar between the groups. The inhibition of IKCa/SKCa channels (TRAM-34 plus UCL1684) or BKCa channels (iberiotoxin) reduced ISO-induced relaxation only in Uni rats and abolished the relaxation differences between the groups. The expression of SKCa channel was decreased in DOCA-salt arteries. The expression of BKCa channel ? subunit was increased whereas the expression of BKCa channel ? subunit was decreased in DOCA-salt arteries. The expression of receptor for activated C kinase 1 (RACK1), which is a binding protein for BKCa channel and negatively modulates its activity, was increased in DOCA-salt arteries. These results suggest that the impairment of ?-AR-mediated relaxation in DOCA-salt mesenteric arteries may be attributable to altered IKCa/SKCa and/or BKCa channels activities rather than cAMP/PKA pathway. Impaired ?-AR-stimulated BKCa channel activity may be due to the imbalance between its subunit expressions and RACK1 upregulation. PMID:22388053

  15. Portal hypertension induced by congenital hepatic arterioportal fistula: Report of four clinical cases and review of the literature

    PubMed Central

    Zhang, Dan-Ying; Weng, Shu-Qiang; Dong, Ling; Shen, Xi-Zhong; Qu, Xu-Dong

    2015-01-01

    Intrahepatic arterioportal fistula (IAPF) can be caused by many secondary factors. We report four cases of portal hypertension that were eventually determined to be caused by congenital hepatic arterioportal fistula. The clinical manifestations included ascites, variceal hemorrhage and hepatic encephalopathy. Computed tomography scans from all of the patients revealed the early enhancement of the portal branches in the hepatic arterial phase. All patients were diagnosed using digital subtraction angiography (DSA). DSA before embolization revealed an arteriovenous fistula with immediate filling of the portal venous radicles. All four patients were treated with interventional embolization. The four patients remained in good condition throughout follow-up and at the time of publication. IAPF is frequently misdiagnosed due to its rarity; therefore, clinicians should consider IAPF as a potential cause of non-cirrhotic portal hypertension. PMID:25717263

  16. Peroxisome proliferator-activated receptor-? activator fenofibrate prevents high-fat diet-induced renal lipotoxicity in spontaneously hypertensive rats

    Microsoft Academic Search

    Seok Joon Shin; Ji Hee Lim; Sungjin Chung; Dong-Ye Youn; Hyun Wha Chung; Hyung Wook Kim; Jeong-Hwa Lee; Yoon Sik Chang; Cheol Whee Park

    2009-01-01

    We investigated the effects of a high-fat (HF) diet and peroxisome proliferator-activated receptor (PPAR)-? activation on the intrarenal lipotoxicity associated with the renin–angiotensin system (RAS) and oxidative stress using spontaneously hypertensive (SHR) rats. Male SHR and Wistar–Kyoto (WKY) rats at 8 weeks of age were fed either a normal-fat diet or an HF diet without or with fenofibrate treatment for

  17. Immunization with an ApoB-100 Related Peptide Vaccine Attenuates Angiotensin-II Induced Hypertension and Renal Fibrosis in Mice

    PubMed Central

    Honjo, Tomoyuki; Chyu, Kuang-Yuh; Dimayuga, Paul C.; Lio, Wai Man; Yano, Juliana; Trinidad, Portia; Zhao, Xiaoning; Zhou, Jianchang; Cercek, Bojan; Shah, Prediman K.

    2015-01-01

    Recent studies suggest the potential involvement of CD8+ T cells in the pathogenesis of murine hypertension. We recently reported that immunization with apoB-100 related peptide, p210, modified CD8+ T cell function in angiotensin II (AngII)-infused apoE (-/-) mice. In this study, we hypothesized that p210 vaccine modulates blood pressure in AngII-infused apoE (-/-) mice. Male apoE (-/-) mice were immunized with p210 vaccine and compared to unimmunized controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII for 4 weeks. At 13 weeks of age, p210 immunized mice showed significantly lower blood pressure response to AngII compared to controls. CD8+ T cells from p210 immunized mice displayed a different phenotype compared to CD8+ T cells from unimmunized controls. Serum creatinine and urine albumin to creatinine ratio were significantly decreased in p210 immunized mice suggesting that p210 vaccine had renal protective effect. At euthanasia, inflammatory genes IL-6, TNF-?, and MCP-1 in renal tissue were down-regulated by p210 vaccine. Renal fibrosis and pro-fibrotic gene expression were also significantly reduced in p210 immunized mice. To assess the role of CD8+ T cells in these beneficial effects of p210 vaccine, CD8+ T cells were depleted by CD8 depleting antibody in p210 immunized mice. p210 immunized mice with CD8+ T cell depletion developed higher blood pressure compared to mice receiving isotype control. Depletion of CD8+ T cells also increased renal fibrotic gene expression compared to controls. We conclude that immunization with p210 vaccine attenuated AngII-induced hypertension and renal fibrosis. CD8+ T cells modulated by p210 vaccine could play an important role in the anti-hypertensive, anti-fibrotic and renal-protective effect of p210 vaccine. PMID:26121471

  18. Immunization with an ApoB-100 Related Peptide Vaccine Attenuates Angiotensin-II Induced Hypertension and Renal Fibrosis in Mice.

    PubMed

    Honjo, Tomoyuki; Chyu, Kuang-Yuh; Dimayuga, Paul C; Lio, Wai Man; Yano, Juliana; Trinidad, Portia; Zhao, Xiaoning; Zhou, Jianchang; Cercek, Bojan; Shah, Prediman K

    2015-01-01

    Recent studies suggest the potential involvement of CD8+ T cells in the pathogenesis of murine hypertension. We recently reported that immunization with apoB-100 related peptide, p210, modified CD8+ T cell function in angiotensin II (AngII)-infused apoE (-/-) mice. In this study, we hypothesized that p210 vaccine modulates blood pressure in AngII-infused apoE (-/-) mice. Male apoE (-/-) mice were immunized with p210 vaccine and compared to unimmunized controls. At 10 weeks of age, mice were subcutaneously implanted with an osmotic pump which released AngII for 4 weeks. At 13 weeks of age, p210 immunized mice showed significantly lower blood pressure response to AngII compared to controls. CD8+ T cells from p210 immunized mice displayed a different phenotype compared to CD8+ T cells from unimmunized controls. Serum creatinine and urine albumin to creatinine ratio were significantly decreased in p210 immunized mice suggesting that p210 vaccine had renal protective effect. At euthanasia, inflammatory genes IL-6, TNF-?, and MCP-1 in renal tissue were down-regulated by p210 vaccine. Renal fibrosis and pro-fibrotic gene expression were also significantly reduced in p210 immunized mice. To assess the role of CD8+ T cells in these beneficial effects of p210 vaccine, CD8+ T cells were depleted by CD8 depleting antibody in p210 immunized mice. p210 immunized mice with CD8+ T cell depletion developed higher blood pressure compared to mice receiving isotype control. Depletion of CD8+ T cells also increased renal fibrotic gene expression compared to controls. We conclude that immunization with p210 vaccine attenuated AngII-induced hypertension and renal fibrosis. CD8+ T cells modulated by p210 vaccine could play an important role in the anti-hypertensive, anti-fibrotic and renal-protective effect of p210 vaccine. PMID:26121471

  19. Statins for Treatment of Pulmonary Hypertension

    Microsoft Academic Search

    John L. Faul; Peter N. Kao; Toshihiko Nishimura; Arthur Sung; Hong Hu; Ronald G. Pearl

    By virtue of their multiple actions, including anti-inflammatory, antiproliferative, and pro-apoptotic traits and the ability\\u000a to restore endothelial vasoactive mediator production, statins have been proposed as potential therapies for pulmonary hypertension.\\u000a In experimental studies in rats with pulmonary hypertension induced either by either monocrotaline or hypoxia, statins have\\u000a blunted the severity of pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular

  20. The role of the osteoprotegerin/tumor necrosis factor related apoptosis-inducing ligand axis in the pathogenesis of pulmonary arterial hypertension.

    PubMed

    Lawrie, Allan

    2014-12-01

    Pulmonary arterial hypertension (PAH) is a fatal condition driven by a progressive remodelling of the small pulmonary arteries through sustained vasoconstriction, and vascular cell proliferation. This process causes a substantial reduction in luminal area increasing pulmonary vascular resistance and blood pressure leading to right heart failure. Current medical therapies can alleviate some symptoms and reduce the vasoconstrictive aspects of disease but new treatments are required that target the vascular cell proliferation if we are to develop new therapies. Expression of the tumour necrosis factor related apoptosis-inducing ligand (TRAIL) and osteoprotegerin (OPG) proteins are increased in IPAH. Specifically OPG is increased within the serum of patients with idiopathic pulmonary arterial hypertension (IPAH) and has prognostic utility, and both OPG and TRAIL are increased within pulmonary vascular lesions of patients with IPAH, and are mitogens for pulmonary artery smooth muscle cells in vitro. We have demonstrated that genetic deletion, or antibody blockade of TRAIL prevents, and critically reverses the development of PAH in multiple rodent models. The role OPG plays in this process both through interacting with TRAIL, and indirectly through other mechanisms is currently unclear these but data highlight the critical importance of this pathway in PAH pathogenesis, and its potential for future therapies. PMID:25446166

  1. Comparison of. beta. -adrenergic receptors between different strains of rat with different susceptibility to hypertension: a survey of binding characteristics, responsiveness and corticosteroid induced modulation

    SciTech Connect

    Jazayeri, A.

    1987-01-01

    The objective of this research was two fold: the first objective was to measure ..beta..-adrenergic receptor characteristics (Bmax and Kd) and responsiveness (isoproterenol induced c-AMP production) between different strains of rat with different susceptibility to hypertension. The second objective of this research was to determine if ..beta..-adrenergic receptors of arterial smooth muscle cells (ASMC) can be modulated by corticosteroids. These studies were done under controlled conditions using ASMC grown in culture from the rat aorta. (/sup 3/H)-dihydroalprenolol (DHA) was used to measure ..beta..-adrenergic receptor binding characteristics (Kd and Bmax). Scatchard analysis of (/sup 3/H)-DHA binding revealed one class of binding sites with affinity in the range of 100 pM. (/sup 3/H)-DHA binding comparison between Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) revealed that the Bmax for SHR was significantly lower than WKY. However, isoproterenol stimulated c-AMP production by SHR, is significantly higher than WKY. Fischer 344 rats, showed similar Bmax, Kd, and responsiveness as WKY rats. Dahl-sensitive and Dahl-resistant rats had equal Bmax and Kd measured by (/sup 3/H)-DHA binding.

  2. Effects of Single Drug and Combined Short-term Administration of Sildenafil, Pimobendan, and Nicorandil on Right Ventricular Function in Rats With Monocrotaline-induced Pulmonary Hypertension.

    PubMed

    Nakata, Telma M; Tanaka, Ryou; Yoshiyuki, Rieko; Fukayama, Toshiharu; Goya, Seijiro; Fukushima, Ryuji

    2015-06-01

    This study was designed to assess the progression of pulmonary arterial hypertension (PAH) and the effectiveness of therapy using recently investigated echocardiographic parameters. PAH is characterized by the progressive elevation of pulmonary artery pressure and right ventricular hypertrophy and dysfunction, which ultimately results in right-sided heart failure and death. Echocardiography results and invasive measurements of right and left ventricular systolic pressures were compared after 3-week administrations of sildenafil (S group), pimobendan (P group), nicorandil (N group), and their combinations (SP and SPN groups) in male rats with monocrotaline (MCT)-induced pulmonary hypertension (M group) and without this condition (C group). The groups that received pimobendan alone and in combinations (SP and SPN groups) showed improvement in their echocardiographic parameters of systolic function. A significant improvement of diastolic function was achieved in the SPN group. Invasive measurements showed the most significant decreases of right ventricular systolic pressure in the N and SPN groups, and the use of pimobendan resulted in a comparatively low risk of adverse hemodynamic effects (left ventricular systolic pressure). Although our results suggested the attenuation of PAH severity in all treatment groups, PAH could not be reversed. PMID:25806612

  3. Effects of Single Drug and Combined Short-term Administration of Sildenafil, Pimobendan, and Nicorandil on Right Ventricular Function in Rats With Monocrotaline-induced Pulmonary Hypertension

    PubMed Central

    Tanaka, Ryou; Yoshiyuki, Rieko; Fukayama, Toshiharu; Goya, Seijiro; Fukushima, Ryuji

    2015-01-01

    Abstract: This study was designed to assess the progression of pulmonary arterial hypertension (PAH) and the effectiveness of therapy using recently investigated echocardiographic parameters. PAH is characterized by the progressive elevation of pulmonary artery pressure and right ventricular hypertrophy and dysfunction, which ultimately results in right-sided heart failure and death. Echocardiography results and invasive measurements of right and left ventricular systolic pressures were compared after 3-week administrations of sildenafil (S group), pimobendan (P group), nicorandil (N group), and their combinations (SP and SPN groups) in male rats with monocrotaline (MCT)-induced pulmonary hypertension (M group) and without this condition (C group). The groups that received pimobendan alone and in combinations (SP and SPN groups) showed improvement in their echocardiographic parameters of systolic function. A significant improvement of diastolic function was achieved in the SPN group. Invasive measurements showed the most significant decreases of right ventricular systolic pressure in the N and SPN groups, and the use of pimobendan resulted in a comparatively low risk of adverse hemodynamic effects (left ventricular systolic pressure). Although our results suggested the attenuation of PAH severity in all treatment groups, PAH could not be reversed. PMID:25806612

  4. Enhanced expression of epithelial sodium channels causes salt-induced hypertension in mice through inhibition of the ?2-isoform of Na+, K+-ATPase

    PubMed Central

    Leenen, Frans H H; Hou, Xiaohong; Wang, Hong-Wei; Ahmad, Monir

    2015-01-01

    Knockout of the Nedd4-2 gene in mice results in overexpression of epithelial sodium channels (ENaC) on the plasma membrane in the kidney, choroid plexus and brain nuclei. These mice exhibit enhanced pressor responses to CSF [Na+] as well as dietary salt-induced hypertension which both can be blocked by central infusion of the ENaC blocker benzamil. Functional studies suggest that ENaC activation in the CNS results in release of endogenous ouabain (EO) and inhibition of the ?2-isoform of Na+, K+-ATPase. To test this concept more specifically, we studied Nedd4-2?/? mice expressing the ouabain-resistant -isoform of Na+, K+-ATPase. Intracerebroventricular (icv) infusion of Na+-rich aCSF (225 mmol/L Na+ at 0.4 ?L/min) increased MAP by 10–15 mmHg in wild-type mice and by 25–30 mmHg in Nedd4-2?/? mice, but by only ~5 mmHg in and in /Nedd4-2?/? mice. Icv infusion of EO-binding Fab fragments also blocked the BP response in Nedd4-2?/? mice. In Nedd4-2?/? mice, 8% high-salt diet increased MAP by 25–30 mmHg, but in /Nedd4-2?/? mice, it increased by only 5–10 mmHg. In contrast, Nedd4-2?/? or did not affect the hypertension caused by sc infusion of Ang II. These findings substantiate the concept that enhanced ENaC activity causes salt-induced pressor responses mainly through EO inhibiting the ?2-isoform of Na+, K+-ATPase in the brain. PMID:25991719

  5. Time-Induced Progressive Alteration of Kir Current in Cerebral Smooth Muscle Cells of Stroke-Prone Spontaneously Hypertensive Rats

    PubMed Central

    Bastide, Michčle; Ouk, Thavarak; Bordet, Régis

    2013-01-01

    We investigated the involvement of potassium inward rectifier current (Kir) impairment in smooth muscle cells of cerebral arteries under the condition of increased susceptibility of stroke, in spontaneously hypertensive stroke-prone (SHRsp) rats compared to spontaneously hypertensive (SHR) ones as well as to controls (WKY). Kir current was studied with whole-cell patch-clamp techniques on freshly isolated single smooth muscle cells (SMC) of middle cerebral artery (MCA) from SHRsp, SHR, and WKY male rats (are range 12–32 weeks). A significant and progressive Kir current density reduction was observed on SMC of SHRsp rats from the 22nd week of age on, as opposed to the Kir current density stability observed over the same time in the SMC of WKY and SHR rats. The Kir density alteration was correlated to the age of the SHRsp animals. These results suggest that in the cerebral vascular smooth muscle cells of SHRsp rats, there is a progressive Kir channel impairment, leading to a reduction of Kir current density. This impairment may underpin a lack of vasodilation of the MCA and be implicated in the stroke-proneness observed on SHRsp animals. PMID:23710341

  6. Significance of echocardiographic assessment for right ventricular function after balloon pulmonary angioplasty in patients with chronic thromboembolic induced pulmonary hypertension.

    PubMed

    Tsugu, Toshimitsu; Murata, Mitsushige; Kawakami, Takashi; Yasuda, Risako; Tokuda, Hanako; Minakata, Yugo; Tamura, Yuichi; Kataoka, Masaharu; Hayashida, Kentaro; Tsuruta, Hikaru; Maekawa, Yuichiro; Inoue, Soushin; Fukuda, Keiichi

    2015-01-15

    Balloon pulmonary angioplasty (BPA) may improve hemodynamics and exercise tolerance in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We studied consecutive 25 patients with CTEPH who underwent BPA and evaluated hemodynamics by right-sided heart catheterization. Right ventricular (RV) function was assessed before and after BPA by echocardiography including speckle-tracking echocardiography and 3-dimensional echocardiography. BPA improved the mean pulmonary artery pressure, pulmonary vascular resistance, and cardiac index. BPA also ameliorated the 3-dimentional RV volume, RV ejection fraction, and RV systolic peak strain, all of which were significantly correlated with hemodynamic parameters. The changes in cardiac index were significantly correlated with those in 3-dimentional RV volume index. Furthermore, RV dyssynchrony quantified by the RV strain analyses was ameliorated after BPA even in patients with mild pulmonary hypertension, implicating the merit of BPA in this patient population with CTEPH. BPA not only improved the hemodynamics in patients with CTEPH, but also ameliorated RV remodeling and dyssynchrony as assessed by 3-dimensional echocardiography or speckle-tracking echocardiography. Thus, the assessment of RV function may provide valuable information about the appropriate indication for BPA, its efficacy, and the therapeutic goal for patients with CTEPH. PMID:25476559

  7. NF-?B pathway is involved in CRP-induced effects on pulmonary arterial endothelial cells in chronic thromboembolic pulmonary hypertension.

    PubMed

    Wynants, Marijke; Vengethasamy, Leanda; Ronisz, Alicja; Meyns, Bart; Delcroix, Marion; Quarck, Rozenn

    2013-12-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by thrombofibrotic obstruction of proximal pulmonary arteries. The cellular and molecular mechanisms underlying the pathogenesis remain incompletely understood, although we recently evidenced the potential involvement of the inflammatory marker C-reactive protein (CRP). We aimed to investigate the intracellular mechanisms induced by CRP in proximal pulmonary arterial endothelial cells (PAEC). PAEC were isolated from vascular material obtained during pulmonary endarterectomy. RNA was extracted from CRP-stimulated PAEC, and first-stand cDNA was generated. A RT(2) profiler PCR Array was used to evaluate the expression of 84 key genes related to NF-?B-mediated signal transduction. CRP-induced NF-?B activation was studied. The effects of pyrrolidine-dithio-carbamate ammonium (PDTC), an inhibitor of the NF-?B pathway, were investigated on CRP-induced adhesion of monocytes to PAEC, adhesion molecule expression, endothelin-1 (ET-1), interleukin-6 (IL-6), and von Willebrand factor (vWF) secretion. Compared with nonstimulated PAEC, serotonin receptor 2B was downregulated by 25%, inhibitor of NF-?B kinase subunit epsilon (IKBKE) by 30%, and toll-like receptor-4 and -6 by 18 and 39%, respectively, in CRP-stimulated PAEC. The transcription factor FOS was threefold upregulated. CRP induced RelA/NF-?Bp65 phosphorylation. PDTC dose dependently inhibited the adhesion of monocytes to CRP-stimulated PAEC. PDTC also inhibited the CRP-induced expression of ICAM-1 at the surface of PAEC. PDTC impaired the secretion of ET-1 by 18% and tended to inhibit the secretion of IL-6 by CRP-stimulated PAEC by 46%. PDTC did not inhibit the CRP-induced secretion of vWF. These results suggest an involvement of the NF-?B pathway in mediating different effects of CRP on proximal CTEPH-PAEC. PMID:24097561

  8. Types of Pulmonary Hypertension

    MedlinePLUS

    ... that group 1 is called pulmonary arterial hypertension (PAH) and groups 2 through 5 are called pulmonary ... hypertension.) Group 1 Pulmonary Arterial Hypertension Group 1 PAH includes: PAH that has no known cause. PAH ...

  9. Hypertension, Cardiac Hypertrophy, and Impaired Vascular Relaxation Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin are Associated with Increased Superoxide

    PubMed Central

    Kopf, Phillip G.; Huwe, Janice K.

    2009-01-01

    The mechanisms by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases the incidence of human cardiovascular disease are not known. We investigated the degree to which cardiovascular disease develops in mice following subchronic TCDD exposure. Adult male C57BL/6 mice were dosed with vehicle or 300 ng TCDD/kg by oral gavage three times per week for 60 days. Blood pressure was recorded by radiotelemetry and aortic endothelial function was assessed by acetylcholine-induced vasorelaxation. Mean arterial pressure of TCDD-exposed mice was increased significantly by day 4 and between days 7–10, 25–35, and 45–60 with two periods of normalization on days 11–24 and days 36–39. Consistent with a prolonged period of systemic hypertension, heart weight was increased and was associated with concentric left ventricular hypertrophy. Significant increases in superoxide production also were observed in the kidney, heart, and aorta of TCDD-exposed mice. Furthermore, increased aortic superoxide resulted in endothelial dysfunction as demonstrated by significant impairment of acetylcholine-induced vasorelaxation in TCDD-exposed mice, which was restored by tempol, a superoxide dismutase (SOD) mimetic. Our model is the first to definitely demonstrate that sustained AhR activation by TCDD increases blood pressure and induces cardiac hypertrophy, which may be mediated, in part, by increased superoxide. PMID:18850075

  10. Treating Hypertension in Pregnancy.

    PubMed

    Schlembach, Dietmar; Homuth, Volker; Dechend, Ralf

    2015-08-01

    Hypertension is present in about 10 % of all pregnancies. The frequency of chronic hypertension and that of gestational hypertension is increasing. The management of pregnant women with hypertension remains a significant, but controversial, public health problem. Although treatment of hypertension in pregnancy has shown to reduce maternal target organ damage, considerable debate remains concerning treatment. We review current evidence regarding treatment goals, the ideal treatment starting time, and which drugs are available for the treatment of hypertension in pregnancy. PMID:26126778

  11. Managing hypertension by polyphenols.

    PubMed

    Fernández-Arroyo, Salvador; Camps, Jordi; Menendez, Javier A; Joven, Jorge

    2015-06-01

    Some polyphenols, obtained from plants of broad use, induce a favorable endothelial response in hypertension and beneficial effects in the management of other metabolic cardiovascular risks. Previous studies in our laboratories using the calyces of Hibiscus sabdariffa as a source of polyphenols show that significant effects on hypertension are noticeable in humans only when provided in high amounts. Available data are suggestive in animal models and ex vivo experiments, but data in humans are difficult to acquire. Additionally, and despite the low bioavailability of polyphenols, intervention studies provide evidence for the protective effects of secondary plant metabolites. Assumptions on public health benefits are limited by the lack of scientific knowledge, robust data derived from large randomized clinical trials, and an accurate assessment of the bioactive components provided by common foodstuff. Because it is likely that clinical effects are the result of multiple interactions among different polyphenols rather than the isolated action of unique compounds, to provide polyphenol-rich botanical extracts as dietary supplements is a suggestive option. Unfortunately, the lack of patent perspectives for the pharmaceutical industries and the high cost of production and release for alimentary industries will hamper the performance of the necessary clinical trials. Here we briefly discuss whether and how such limitations may complicate the extensive use of plant-derived products in the management of hypertension and which steps are the necessary to deal with the predictable complexity in a possible clinical practice. PMID:25714729

  12. Neonatal hypertension.

    PubMed

    Batisky, Donald L

    2014-09-01

    The incidence of neonatal hypertension (HTN) remains low, at less than 2%, and its etiology is varied. Strict definitions of HTN in neonates are unavailable, and the decision to treat is based on opinion rather than evidence. More studies are needed to define normal blood pressure in neonates and to refine current reference values, thus permitting a better definition of HTN. Most causes of neonatal HTN, the most common of which seems to be renovascular disease, are determined by history and basic clinical investigations. Treatment is guided by clinical judgment and expert opinion, given the limited number of clinical trials. PMID:25155725

  13. Cardiac Metabolic Alterations in Hypertensive Obese Pigs.

    PubMed

    Zhang, Xin; Li, Zi-Lun; Eirin, Alfonso; Ebrahimi, Behzad; Pawar, Aditya S; Zhu, Xiang-Yang; Lerman, Amir; Lerman, Lilach O

    2015-08-01

    Obesity and hypertension are major risk factors for cardiovascular diseases, and their growing coexistence accounts for an increase in adverse cardiac events, but the mechanisms are yet to be determined. We hypothesized that obesity exacerbates mitochondrial dysregulation imposed by hypertension and augments left ventricular dysfunction. Obesity-prone Ossabaw pigs were randomized to lean (standard diet) and obese (high-fat diet), without (Lean-sham and Obese-sham) or with renovascular hypertension (Lean-hypertension and Obese-hypertension), induced after 12 weeks of diet (n=7 each). Cardiac function, myocardial perfusion and oxygenation, and microvascular remodeling were assessed 4 weeks later. Mitochondrial biogenesis signals and structural proteins, respiratory chain complex activities, and mitochondrial self-degradation were examined, as was fibrosis. Obesity alone exerted no apparent effect on mitochondrial dynamics, but aggravated in hypertensive hearts the reduction of mitochondrial proteins, deoxyribonucleic acid content, and respiratory chain complex IV subunits activity, and amplified mitochondrial self-degradation. Synergistic interaction of obesity with hypertension also exacerbated myocardial fibrosis and left ventricular diastolic dysfunction. Mitochondrial content, respiratory chain complex IV subunits activity, and mitophagy were correlated with myocardial fibrosis. These findings suggest that obesity aggravates in renovascular hypertension cardiac mitochondrial aberrations. Mitochondrial function may regulate the progression of cardiac injury and functional deterioration in hypertension concomitant with obesity. PMID:26077566

  14. Correlation of bevacizumab-induced hypertension and outcome in the BOXER study, a phase II study of capecitabine, oxaliplatin (CAPOX) plus bevacizumab as peri-operative treatment in 45 patients with poor-risk colorectal liver-only metastases unsuitable for upfront resection

    PubMed Central

    Dewdney, A; Cunningham, D; Barbachano, Y; Chau, I

    2012-01-01

    Background: Bevacizumab is commonly used in combination with chemotherapy in the treatment of metastatic colorectal cancer, but to date, despite extensive research, no predictive or prognostic biomarkers for bevacizumab have been identified. The development of bevacizumab-induced arterial hypertension has recently been suggested as a potential predictive biomarker. Methods: Blood pressure was recorded during the BOXER study, a phase II study of capecitabine, oxaliplatin (CAPOX) plus bevacizumab as peri-operative treatment in 45 patients with poor-risk colorectal liver-only metastases unsuitable for upfront resection. In this analysis, the development of bevacizumab-induced hypertension was correlated with clinical outcomes. Results: Fifteen percent of patients developed ?grade 1 hypertension while receiving neoadjuvant chemotherapy, and 4% developed grade 3 hypertension. There was no correlation between the development of hypertension and radiological response rate (P=0.642), progression-free survival (P=0.644) or overall survival (P=0.480) in those who developed hypertension compared with those who did not. Conclusion: Bevacizumab-induced hypertension did not predict radiological response or survival in our study. The results highlight a number of important issues regarding the use of hypertension as a biomarker. PMID:22531628

  15. Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

    PubMed Central

    2012-01-01

    Background Previous reports suggest that omega-3 (n-3) polyunsaturated fatty acids (PUFA) supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD. Methods We used spontaneously hypertensive rats (SHR). SHR dams were given n-3 PUFA (EPA and DHA)-enriched feed (n-6/n-3 of 1:2.7) during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY) control rats were given control-feed (n-6/n-3 of 7:1). During postnatal days (PND) 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography. Results n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms in both sexes. PMID:23228189

  16. Restless legs syndrome and hypertension in Chinese pregnant women.

    PubMed

    Ma, Shengli; Shang, Xiaoping; Guo, Yu; Liu, Gangqiong; Yang, Jinjian; Xue, Rui

    2015-06-01

    Hypertension is a common complication of pregnancy, and studies show that pregnant women are more likely to suffer from restless legs syndrome (RLS). Pregnant women with hypertension and RLS often experience disrupted sleep patterns because of activation of the nervous system. The present study aimed to clarify the relationship between hypertension and RLS in pregnant women, and their impact on sleep. We enrolled 3,781 pregnant women who were admitted at our hospital for delivery between May 2011 and May 2014. The face-to-face questionnaire used to gather data included the International RLS Study Group criteria for diagnosis, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and hypertension diagnosis. Depending on the time of occurrence of hypertension, it was divided into two different types: pregnancy-induced hypertension and chronic hypertension in pregnancy. Out of 3,781 patients, 453 fulfilled the diagnostic criteria for RLS and 486 met the diagnostic criteria for hypertension. Among patients with RLS, prophylactic iron supplementation was less frequently taken during pregnancy. Pregnancy-induced hypertension, rather than chronic hypertension in pregnancy, was found to be more frequent in patients with RLS; pregnant women with RLS had higher PSQI and ESS scores than pregnant controls. In our study, RLS was frequent in pregnant women, especially in those without prophylactic iron supplementation. Patients with RLS described more serious sleep disruption and excessive daytime sleepiness (EDS). In addition, pregnancy-induced hypertension was more common in patients with RLS. PMID:25647293

  17. The dual AngII/AVP receptor gene N119S/C163R variant exhibits sodium-induced dysfunction and cosegregates with salt-sensitive hypertension in the Dahl salt-sensitive hypertensive rat model.

    PubMed Central

    Ruiz-Opazo, Nelson; Lopez, Lyle V.; Herrera, Victoria L. M.

    2002-01-01

    BACKGROUND: Essential hypertension is a prevalent complex polygenic disease and a major risk factor for cardiovascular disease, the leading cause of death in developed countries. Because of its complex and multifactorial nature, its genetic determinants still remain largely unknown. The Dahl salt-sensitive hypertensive rat model exhibits impaired sodium handling, which is hypothesized to play a key role in the pathophysiology of polygenic hypertension. Thus, genes associated with renal regulation of salt and water balance are a priori likely candidates for a causative role in hypertension pathogenesis. The functional properties and renal-specific expression of the recently characterized AngII/AVP receptor suggest a putative modulator role in tubular sodium and fluid reabsorption. Based on these observations, we investigated the potential involvement of the AngII/AVP receptor in salt-sensitive hypertension. MATERIALS AND METHODS:We performed cosegregation analysis of the AngII/AVP receptor locus with salt-sensitive hypertension in an F2 (Dahl S X Dahl salt-resistant [R]) hybrid male cohort characterized for blood pressure by radiotelemetry after 8 weeks of high salt challenge. Further molecular analysis was done to identify putative AngII/AVP receptor molecular variants that could account for the AngII/ AVP receptor involvement in salt-sensitive hypertension pathogenesis. RESULTS:The AngII/AVP receptor was mapped to rat chromosome 1, 1.7 cM centromeric to the D1Rat188 marker by radiation hybrid mapping analysis. Quantitative trait locus (QTL) analysis detected a highly significant linkage of the AngII/AVP receptor locus with high blood pressure (LRS = 13.8, p= 0.0002). Molecular characterization of the Dahl S and Dahl R AngII/AVP receptor cDNAs revealed two amino acid substitutions in the Dahl S AngII/AVP receptor (N119S, C163R) when compared to the Dahl R AngII/AVP receptor. These mutations are associated with an increased receptor affinity for both ligands (AVP and AngII) and an enhanced G(s)-coupling by the receptor resulting in increased activation of adenylate cyclase with concomitant increase in cAMP production. CONCLUSIONS: The observed molecular dysfunction in the Dahl S AngII/AVP receptor is consistent with increased tubular sodium and fluid reabsorption observed in Dahl S rats. Interestingly, the AngII/AVPr locus is within the narrowed chromosome 1 QTL region for blood pressure detected in different rat intercross linkage analyses. Altogether, the data strongly suggest that the AngII/AVP receptor is a hypertension susceptibility gene in the Dahl S rat model, as well as raises the hypothesis that it too underlies the chromosome 1 blood pressure QTL identified in other hypertension rat models. PMID:11984003

  18. Calcineurin inhibitors and hypertension: a role for pharmacogenetics?

    PubMed

    Moes, Arthur D; Hesselink, Dennis A; Zietse, Robert; van Schaik, Ron H N; van Gelder, Teun; Hoorn, Ewout J

    2014-06-01

    Hypertension is a common side effect of calcineurin inhibitors (CNIs), which are drugs used to prevent rejection after transplantation. Hypertension after kidney transplantation has been associated with earlier graft failure and higher cardiovascular mortality in the recipient. Recent data indicate that enzymes and transporters involved in CNI pharmacokinetics and pharmacodynamics, including CYP3A5, ABCB1, WNK4 and SPAK, are also associated with salt-sensitive hypertension. These insights raise the question whether polymorphisms in the genes encoding these proteins increase the risk of CNI-induced hypertension. Predicting who is at risk for CNI-induced hypertension may be useful for when selecting specific interventions, including dietary salt restriction, thiazide diuretics or a CNI-free immunosuppressive regimen. This review aims to explore the pharmacogenetics of CNI-induced hypertension, highlighting the knowns and unknowns. PMID:25141899

  19. Low renin hypertension

    PubMed Central

    Sahay, Manisha; Sahay, Rakesh K.

    2012-01-01

    Low renin hypertension is an important and often underdiagnosed cause of hypertension. It may be associated with high aldosterone levels as in Conn's syndrome or low aldosterone levels as in Liddle syndrome, and syndrome of apparent mineralocorticoid excess, glucocorticoid remediable hypertension etc. Some forms of essential hypertension are also associated with low renin levels. Hypokalemia may be an important finding in low renin hypertension. The aldosterone to renin ratio helps in correct diagnosis. The treatment varies with etiology hence an accurate diagnosis is essential. Aldosterone antagonists play an important role in medical management of some varieties of low renin hypertension. PMID:23087856

  20. Experimental models of melatonin-deficient hypertension.

    PubMed

    Simko, Fedor; Reiter, Russel J; Pechanova, Olga; Paulis, Ludovit

    2013-01-01

    Melatonin secreted by the pineal gland plays an important role in the regulation of blood pressure (BP) and its administration reduces hypertension both in animals and humans. There are two experimental models of melatonin-deficient hypertension: one induced by pinealectomy and another by continuous 24 hour exposure to light. Both models cause melatonin deficiency and prevent darkness-mediated nocturnal melatonin secretion and are associated with increased BP and myocardial, vascular and renal dysfunction. These models also lead to neurohumoral activation of the renin-angiotensin system, sympathetic nervous system, adrenocorticotrophin-glucocorticoid axis and cause insulin resistance. Together, these alterations contribute to rise in blood pressure by vasoconstrictive or circulatory fluid volume overload. The light induced hypertension model mimics the melatonin deficiency in patients with insufficient nocturnal BP decline, in those who have night shift or who are exposed to environmental light pollution. For this reason, this model is useful in development of anti-hypertensive drugs. PMID:23276947

  1. Psychosocial factors in the development of hypertension.

    PubMed

    Steptoe, A

    2000-07-01

    The role of psychosocial factors in human hypertension is being investigated with three research strategies: epidemiological studies of blood pressure, psychological characteristics and life experience in population samples, naturalistic studies of the covariation between blood pressure, psychological state and everyday life events, and experimental studies of cardiovascular and neuroendocrine responses to behavioural stimuli. This article summarizes recent research on hypertension and psychological traits, job characteristics and social support, emphasizing the convergent knowledge deriving from complementary research strategies. The roles of stress-induced cardiovascular responses and prejudicial life styles in mediating influences on risk of hypertension are discussed. PMID:10949069

  2. Sex-specific immune modulation of primary hypertension.

    PubMed

    Sandberg, Kathryn; Ji, Hong; Hay, Meredith

    2015-04-01

    It is well known that the onset of essential hypertension occurs earlier in men than women. Numerous studies have shown sex differences in the vasculature, kidney and sympathetic nervous system contribute to this sex difference in the development of hypertension. The immune system also contributes to the development of hypertension; however, sex differences in immune system modulation of blood pressure (BP) and the development of hypertension has only recently begun to be explored. Here we review findings on the effect of one's sex on the immune system and specifically how these effects impact BP and the development of primary hypertension. We also propose a hypothesis for why mechanisms underlying inflammation-induced hypertension are sex-specific. These studies underscore the value of and need for studying both sexes in the basic science exploration of the pathophysiology of hypertension as well as other diseases. PMID:25498375

  3. Work-Related Maternal Risk Factors and the Risk of Pregnancy Induced Hypertension and Preeclampsia during Pregnancy. The Generation R Study

    Microsoft Academic Search

    Jaap Jan Nugteren; Claudia A. Snijder; Albert Hofman; Vincent W. V. Jaddoe; Eric A. P. Steegers; Alex Burdorf

    2012-01-01

    ObjectiveTo study the associations between physically demanding work and occupational exposure to chemicals and hypertensive disorders during pregnancy within a large birth cohort study, the Generation R Study.MethodsAssociations between occupational characteristics and hypertensive disorders during pregnancy were studied in 4465 pregnant woman participating in a population-based prospective cohort study from early pregnancy onwards in the Netherlands (2002–2006). Mothers who filled

  4. A new model of Type 2 (non-insulin-dependent) diabetes mellitus in spontaneously hypertensive rats: diabetes induced by neonatal streptozotocin treatment

    Microsoft Academic Search

    M. Iwase; M. Kikuchi; K. Nunoi; M. Wakisaka; Y. Maki; S. Sadoshima; M. Fujishima

    1986-01-01

    Summary  This study was designed to develop an animal model of Type 2 (non-insulin-dependent) diabetes with persistent hypertension. Male spontaneously hypertensive rats were treated with 25.0, 37.5, 50.0, 62.5 or 75.0 mg\\/kg of streptozotocin given intraperitoneally at 2 days of age and maintained for 12 weeks. In the rats which received 50.0 mg\\/kg or more streptozotocin, overt hyperglycaemia gradually and consistently

  5. Secondary Forms of Hypertension

    Microsoft Academic Search

    Kjell Tullus

    \\u000a In most studies, hypertension in children has been secondary to an identifiable cause in a large majority of those studied\\u000a (1,2). This has changed during the relatively recent epidemic of childhood obesity, where primary hypertension in many centers\\u000a now is the most common cause form of hypertension (3). In adults primary hypertension is the dominating diagnosis. This chapter will discuss

  6. Hypertensive crisis in children

    Microsoft Academic Search

    Jayanthi Chandar; Gastón Zilleruelo

    Hypertensive crisis is rare in children and is usually secondary to an underlying disease. There is strong evidence that the\\u000a renin-angiotensin system plays an important role in the genesis of hypertensive crisis. An important principle in the management\\u000a of children with hypertensive crisis is to determine if severe hypertension is chronic, acute, or acute-on-chronic. When it\\u000a is associated with signs

  7. Hypertension artérielle et anesthésie

    Microsoft Academic Search

    T Barbry; P Coriat

    2004-01-01

    Hypertension is one of the most important risk factors for cerebrovascular disease and ischaemic heart disease. Postoperative adverse outcomes of hypertension include cardiac death, left ventricular hypertrophy (with impaired diastolic function) leading to ventricular failure, myocardial ischaemia and infarction, renal damage and cerebrovascular accidents. The role of the anaesthetist for patients suffering from chronic hypertension goes beyond that in most

  8. Diabetes and arterial hypertension

    Microsoft Academic Search

    P. L. Drury

    1983-01-01

    Summary  The epidemiology, pathogenesis, significance and management of hypertension in diabetic subjects are discussed. In Type 1 diabetes the presence of diastolic hypertension is closely related to the presence of diabetic nephropathy, from the stage of persistent proteinuria onwards. There may also be some elevation of systolic pressure. The apparent increased prevalence of hypertension in Type 2 diabetes is largely explicable,

  9. Chronic Thromboembolic Pulmonary Hypertension

    Microsoft Academic Search

    William R. Auger; Nick H. Kim; Terence K. Trow

    2010-01-01

    hronic thromboembolic pulmonary hypertension (CTEPH) has emerged as one of the leading causes of severe pulmonary hypertension. The disease is notoriously underdiagnosed, and the true prevalence is still unclear. CTEPH is characterized by intraluminal thrombus organiza- tion and fibrous stenosis or complete obliteration of pulmo- nary arteries.1 The consequence is an increased pulmonary vascular resistance resulting in pulmonary hypertension and

  10. Involvement of the atrial natriuretic peptide in the reduction of arterial pressure induced by swimming but not by running training in hypertensive rats.

    PubMed

    Endlich, Patrick W; Firmes, Luciana B; Gonçalves, Washington L S; Gouvea, Sonia A; Moysés, Margareth R; Bissoli, Nazaré S; Reis, Adelina M; Abreu, Glaucia R

    2011-08-01

    The aim of this study was to compare, under resting conditions, the influence of chronic training in swimming or running on mean arterial pressure (MAP) and the involvement of the natriuretic peptide system in this response. Two-month-old male spontaneously hypertensive rats (SHR) were divided into three groups-sedentary (SD), swimming (SW) and running (RN)-and were trained for eight weeks under regimens of similar intensities. Atria tissue and plasma atrial natriuretic peptide (ANP) concentrations were measured by radioimmunoassay. ANP mRNA levels in the right and left atria as well as the natriuretic peptide receptors (NPR), NPR-A and NPR-C, mRNA levels in the kidney were determined by real-time PCR. Autoradiography was used to quantify NPR-A and NPR-C in mesenteric adipose tissue. Both training modalities, swimming and running, reduced the mean arterial pressure (MAP) of SHR. Swimming, but not running, training increased plasma levels of ANP compared to the sedentary group (P<0.05). Expression of ANP mRNA in the left atrium was reduced in the RN compared to the SD group (P<0.05). Expression of NPR-A and NPR-C in the kidneys of the SW group decreased significantly (P<0.05) compared to the SD group. Although swimming increased (125)I-ANP binding to mesenteric adipose tissue, displacement by c-ANF was reduced, indicating a reduction of NPR-C. These results suggest that the MAP reduction induced by exercise in SHR differs in its mechanisms between the training modalities, as evidenced by the finding that increased levels of ANP were only observed after the swimming regimen. PMID:21762739

  11. A single exposure to particulate or gaseous air pollution increases the risk of aconitine-induced cardiac arrhythmia in hypertensive rats.

    PubMed

    Hazari, Mehdi S; Haykal-Coates, Najwa; Winsett, Darrell W; Costa, Daniel L; Farraj, Aimen K

    2009-12-01

    Epidemiological studies demonstrate an association between arrhythmias and air pollution. Aconitine-induced cardiac arrhythmia is widely used experimentally to examine factors that alter the risk of arrhythmogenesis. In this study, Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats acutely exposed to synthetic residual oil fly ash (s-ROFA) particles (450 mug/m(3)) were "challenged" with aconitine to examine whether a single exposure could predispose to arrhythmogenesis. Separately, SH rats were exposed to varied particulate matter (PM) concentrations (0.45, 1.0, or 3.5 mg/m(3) s-ROFA), or the irritant gas acrolein (3 ppm), to better assess the generalization of this challenge response. Rather than directly cause arrhythmias, we hypothesized that inhaled air pollutants sensitize the heart to subsequent dysrhythmic stimuli. Twenty-four hour postexposure, urethane-anesthetized rats were monitored for heart rate (HR), electrocardiogram, and blood pressure (BP). SH rats had higher baseline HR and BP and significantly longer PR intervals, QRS duration, QTc, and JTc than WKY rats. PM exposure caused a significant increase in the PR interval, QRS duration, and QTc in WKY rats but not in SH rats. Heart rate variability was significantly decreased in WKY rats after PM exposure but increased in SH rats. Cumulative dose of aconitine that triggered arrhythmias in air-exposed SH rats was lower than WKY rats and even lower for each strain postexposure. SH rats exposed to varied concentrations of PM or acrolein developed arrhythmia at significantly lower doses of aconitine than controls; however, there was no PM concentration-dependent response. In conclusion, a single exposure to air pollution may increase the sensitivity of cardiac electrical conduction to disruption. Moreover, there seem to be host factors (e.g., cardiovascular disease) that increase vulnerability to triggered arrhythmias regardless of the pollutant or its concentration. PMID:19748997

  12. Chronic central nervous system MC3/4R blockade attenuates hypertension induced by nitric oxide synthase inhibition but not by angiotensin II infusion.

    PubMed

    da Silva, Alexandre A; do Carmo, Jussara M; Dubinion, John H; Bassi, Mirian; Mokhtarpouriani, Kasra; Hamza, Shereen M; Hall, John E

    2015-01-01

    We examined whether central melanocortin 3 and 4 receptor (MC3/4R) blockade attenuates the blood pressure (BP) responses to chronic L-NAME or angiotensin II (Ang II) infusion in Sprague-Dawley rats implanted with telemetry transmitters, venous catheters, and intracerebroventricular cannula into the lateral ventricle. After 5 days of control measurements, L-NAME (10 ?g/kg/min IV, groups 1 and 2) or Ang II (10 ng/kg/min IV, groups 3 and 4) were infused for 24 days, and starting on day 7 of L-NAME or Ang II infusion, the MC3/4R antagonist SHU-9119 (24 nmol/d, n=6/group; groups 1 and 3) or vehicle (saline 0.5 ?L/h, n=6/group; groups 2 and 4) was infused intracerebroventricularly for 10 days. A control normotensive group also received SHU-9119 for 10 days (n=5). L-NAME and Ang II increased BP by 40±3 and 56±5 mm Hg, respectively, although heart rate was slightly reduced. MC3/4R blockade doubled food intake and reduced heart rate (?40 to ?50 bpm) in all groups. MC3/4R blockade caused only a small reduction in BP in normotensive group (4 mm Hg) and no change in rats receiving Ang II, although markedly reducing BP by 21±4 mm Hg in L-NAME-treated rats. After SHU-9119 infusion was stopped, food intake, heart rate, and BP gradually returned to values observed before SHU-9119 infusion was started. Ganglionic blockade at the end of L-NAME or Ang II infusion caused similar BP reduction in both groups. These results suggest that the brain MC3/4R contributes, at least in part, to the hypertension induced by chronic L-NAME infusion but not by Ang II. PMID:25287400

  13. Epoxyeicosatrienoic acid analog attenuates angiotensin II hypertension and kidney injury.

    PubMed

    Khan, Abdul Hye; Falck, John R; Manthati, Vijaya L; Campbell, William B; Imig, John D

    2014-01-01

    Epoxyeicosatrienoic acids (EETs) contribute to blood pressure regulation leading to the concept that EETs can be therapeutically targeted for hypertension and the associated end organ damage. In the present study, we investigated anti-hypertensive and kidney protective actions of an EET analog, EET-B in angiotensin II (ANG II)-induced hypertension. EET-B was administered in drinking water for 14 days (10 mg/kg/d) and resulted in a decreased blood pressure elevation in ANG II hypertension. At the end of the two-week period, blood pressure was 30 mmHg lower in EET analog-treated ANG II hypertensive rats. The vasodilation of mesenteric resistance arteries to acetylcholine was impaired in ANG II hypertension; however, it was improved with EET-B treatment. Further, EET-B protected the kidney in ANG II hypertension as evidenced by a marked 90% decrease in albuminuria and 54% decrease in nephrinuria. Kidney histology demonstrated a decrease in renal tubular cast formation in EET analog-treated hypertensive rats. In ANG II hypertension, EET-B treatment markedly lowered renal inflammation. Urinary monocyte chemoattractant protein-1 excretion was decreased by 55% and kidney macrophage infiltration was reduced by 52% with EET-B treatment. Overall, our results demonstrate that EET-B has anti-hypertensive properties, improves vascular function, and decreases renal inflammation and injury in ANG II hypertension. PMID:25295006

  14. Probucol reduces oxysterol formation in hypertensive rabbits.

    PubMed

    Hodis, H N; Hashimoto, S; Mack, W J; Sevanian, A

    2000-09-01

    The role of lipid peroxidation during the pathogenesis of atherosclerosis has been described through numerous studies and has provided compelling evidence for free radical-mediated processes that link hypertension with atherosclerosis. However, there remains only limited information concerning peroxidative processes in hypertension and their modulation by antioxidants. In the present study, the formation of cholesterol oxidation products was used as a measure of in vivo lipid peroxidation after hypertension induced by coarctation of the aorta in New Zealand White rabbits. The rabbits were fed a standard chow diet devoid of cholesterol or cholesterol oxidation products such that the measured cholesterol oxides in the plasma and aortic tissues would most plausibly arise from endogenous oxidation of cholesterol. After 12 weeks of hypertension, all of the measured cholesterol oxides increased significantly over baseline levels in the surgically coarctated animals; however, this increase was significantly less in hypertensive probucol-treated animals. Similarly, the cholesterol oxide content of aortic tissue from the surgically coarctated animals was significantly greater than that found in normotensive control aortas, and probucol treatment significantly reduced the increase in cholesterol oxide content of aortic tissue relative to that of hypertensive animals not receiving the antioxidant. These findings in hypertensive animals suggest that cholesterol oxidation products measured in plasma and aortic tissue can be derived from endogenous free radical activity and that this activity is enhanced under specific pathological conditions. PMID:10988278

  15. Exercise-induced arterial hypertension - an independent factor for hypertrophy and a ticking clock for cardiac fatigue or atrial fibrillation in athletes?

    PubMed Central

    Leischik, Roman; Spelsberg, Norman; Niggemann, Hiltrud; Dworrak, Birgit; Tiroch, Klaus

    2014-01-01

    Background : Exercise-induced arterial hypertension (EIAH) leads to myocardial hypertrophy and is associated with a poor prognosis. EIAH might be related to the “cardiac fatigue” caused by endurance training. The goal of this study was to examine whether there is any relationship between EIAH and left ventricular hypertrophy in Ironman-triathletes. Methods: We used echocardiography and spiroergometry to determine the left ventricular mass (LVM), the aerobic/anaerobic thresholds and the steady-state blood pressure of 51 healthy male triathletes. The main inclusion criterion was the participation in at least one middle or long distance triathlon. Results: When comparing triathletes with LVM <220g  and athletes with LVM >220g there was a significant difference between blood pressure values (BP) at the anaerobic threshold (185.2± 21.5 mmHg vs. 198.8 ±22.3 mmHg, p=0.037). The spiroergometric results were: maximum oxygen uptake (relative VO 2max) 57.3 ±7.5ml/min/kg vs. 59.8±9.5ml/min/kg (p=ns). Cut-point analysis for the relationship of BP >170 mmHg at the aerobic threshold and the probability of LVM >220g showed a sensitivity of 95.8%, a specificity of 33.3%, with a positive predictive value of 56.8 %, a good negative predictive value of 90%. The probability of LVM >220g increased with higher BP during exercise (OR: 1.027, 95% CI 1.002-1.052, p= 0.034) or with higher training volume (OR: 1.23, 95% CI 1.04 -1.47, p = 0.019). Echocardiography showed predominantly concentric remodelling, followed by concentric hypertrophy. Conclusion: Significant left ventricular hypertrophy with LVM >220g is associated with higher arterial blood pressure at the aerobic or anaerobic threshold. The endurance athletes with EIAH may require a therapeutic intervention to at least prevent extensive stiffening of the heart muscle and exercise-induced cardiac fatigue. PMID:25132960

  16. Secondary Hypertension in Pregnancy.

    PubMed

    Malha, Line; August, Phyllis

    2015-07-01

    Hypertension is a common medical complication of pregnancy. Although 75-80 % of women with preexisting essential hypertension will have uncomplicated pregnancies, the presence of secondary forms of hypertension adds considerably to both maternal and fetal morbidity and mortality. Renovascular hypertension, pheochromocytoma, and Cushing's syndrome in particular are associated with accelerating hypertension, superimposed preeclampsia, preterm delivery, and fetal loss. Primary aldosteronism is a more heterogeneous disorder; there are well-documented cases where blood pressure and hypokalemia are improved during pregnancy due to elevated levels of progesterone. However, superimposed preeclampsia, worsening hypertension, and early delivery are also reported. When possible, secondary forms of hypertension should be diagnosed and treated prior to conception in order to avoid these complications. PMID:26068655

  17. Cardiopulmonary Responses of Wistar Kyoto, Spontaneously Hypertensive, and Stroke-prone Spontaneously Hypertensive Rats to Particulate Matter (PM) Exposure

    Microsoft Academic Search

    J. Grace Wallenborn; Mette C. Schladweiler; Abraham Nyska; Jo Anne Johnson; Ronald Thomas; Richard H. Jaskot; Judy H. Richards; Allen D. Ledbetter; Urmila P. Kodavanti

    2007-01-01

    Humans with underlying cardiovascular disease, including stroke, are more susceptible to ambient particulate matter (PM)-induced morbidity and mortality. We hypothesized that stroke-prone spontaneously hypertensive rats (SHRSP) would be more susceptible than healthy Wistar Kyoto (WKY) rats to PM-induced cardiac oxidative stress and pulmonary injury. We further postulated that PM-induced injury would be greater in SHRSP than in spontaneously hypertensive rats

  18. [Theoretical considerations and comments on the physiopathology in renovascular hypertension].

    PubMed

    Burnei, Gh; Grigorean, V T; Gavriliu, St; Du?escu, S; Georgescu, I; Iacobini, M; Vlad, C; Stoian, A R; Burnei, A; Neac?u, C M

    2008-01-01

    The researches performed during the last four decades did not elucidate completely the pathogenic mechanism of the renovascular hypertension. The present knowledge considers that the origins of renovascular hypertension are the imbalance between the renal hypotensive system located in the medullar renal site (antihypertensive and hypotensive substances) and the renal hypertensive system (renin-angiotensin-aldosterone) located cortically. As an additional mechanism in producing hypertension is involved the disorder of hydro electrolytic metabolism, as a result of decreased excretory function, inducing an increase of plasmatic natrium level, of volemia and interstitial liquid. PMID:19274913

  19. Top-Down Lipidomics Reveals Ether Lipid Deficiency in Blood Plasma of Hypertensive Patients

    Microsoft Academic Search

    Juergen Graessler; Dominik Schwudke; Peter E. H. Schwarz; Ronny Herzog; Andrej Shevchenko; Stefan R. Bornstein

    2009-01-01

    Background: Dyslipoproteinemia, obesity and insulin resistance are integrative constituents of the metabolic syndrome and are major risk factors for hypertension. The objective of this study was to determine whether hypertension specifically affects the plasma lipidome independently and differently from the effects induced by obesity and insulin resistance. Methodology\\/Principal Findings: We screened the plasma lipidome of 19 men with hypertension and

  20. Hypertension in pregnancy

    Microsoft Academic Search

    R. A. Duckett; L. Kenny; P. N. Baker

    2001-01-01

    Hypertension is associated with between 6–8% of pregnancies and has serious repercussions for both fetal and maternal well being. Hypertension may predate or develop during pregnancy. Pre-eclampsia, arguably the most important cause of hypertension in pregnancy, has a complex aetiology and pathophysiology. Pre-eclampsia is associated with a defect in placentation which may be secondary to abnormal genetic and immunological factors.

  1. Chronic Thromboembolic Pulmonary Hypertension

    Microsoft Academic Search

    Irene M. Lang; Walter Klepetko

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a poorly understood disorder. It is characterized by pulmonary hypertension\\u000a associated with an apparent failure to resolve extensive, typically major-vessel pulmonary thromboemboli. Although CTEPH is\\u000a believed to be a thromboembolic disease, the typical risk factors for venous thromboembolism are absent. According to the\\u000a 2003 Venice classification of pulmonary hypertension, CTEPH represents group IV of

  2. Peroxisome proliferator-activated receptor-c agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents

    Microsoft Academic Search

    Kudret Tureyen; Ramya Kapadia; Kellie K. Bowen; Irawan Satriotomo; Jin Liang; Douglas L. Feinstein; Raghu Vemuganti

    Thiazolidinediones (TZDs) are synthetic agonists of the lig- and-activated transcription factor peroxisome proliferator- activated receptor-c (PPARc). TZDs are known to curtail inflammation associated with peripheral organ ischemia. As inflammation precipitates the neuronal death after stroke, we tested the efficacy of TZDs in preventing brain dam- age following transient middle cerebral artery occlusion (MCAO) in adult rodents. As hypertension and diabetes

  3. Lifestyle and hypertension.

    PubMed

    Beilin, L J; Puddey, I B; Burke, V

    1999-09-01

    Lifestyle factors are critical determinants of blood pressure levels operating against a background of genetic susceptibility. Excess body fat is a predominant cause of hypertension with additive effects of dietary salt, alcohol, and physical inactivity. Controlled trials in hypertensives show blood pressure lowering effects of supplemental potassium, fibre, n-3 fatty acids, and diets rich in fruit and vegetables and low in saturated fats. Some population studies show an inverse relationship between dietary protein and blood pressure levels. Regular coffee drinking raises blood pressure in hypertensives. The role of "stress" remains enigmatic, with "job strain" being a possible independent risk factor for hypertension. PMID:10509554

  4. [Hungarian Hypertension Registry].

    PubMed

    Kiss, István; Kékes, Ede

    2014-05-11

    Today, hypertension is considered endemic throughout the world. The number of individuals with high blood pressure and the increasing risk, morbidity and mortality caused by hypertension despite modern therapy do not decrease sufficiently. Hypertension has become a public health issue. Prevention and effective care require integrated datasets about many features, clinical presentation and therapy of patients with hypertension. The lack of this database in Hungary prompted the development of the registry which could help to provide population-based data for analysis. Data collection and processing was initiated by the Hungarian Society of Hypertension in 2002. Data recording into the Hungarian Hypertension Registry was performed four times (2002, 2005, 2007, 2011) and the registry currently contains data obtained from 108,473 patients. Analysis of these data indicates that 80% of the patients belong to the high or very high cardiovascular risk group. The registry provides data on cardiovascular risk of the hypertensive populations and the effectiveness of antihypertensive therapy in Hungary. Based on international experience and preliminary analysis of data from the Hungarian Hypertension Registry, establishment of hypertension registry may support the effectiveness of public health programs. A further step would be needed for proper data management control and the application of professional principles of evidence-based guidelines in the everyday practice. PMID:24796784

  5. Pediatric endocrine hypertension

    PubMed Central

    Bhavani, Nisha

    2011-01-01

    Endocrine causes of hypertension are rare in children and screening for endocrine hypertension in children should be carried out only after ruling out renal and renovascular causes. Excess levels and/or action of mineralocorticoids associated with low renin levels lead to childhood hypertension and this can be caused by various conditions which are discussed in detail in the article. Childhood pheochromocytomas are being increasingly diagnosed because of the improved application of genetic testing for familial syndromes associated with pheochromocytomas. Adolescents with polycystic ovarian syndrome (PCOS) can also have hypertension associated with their obese phenotype. PMID:22145140

  6. Hypertension in women.

    PubMed

    Rangarajan, U; Kochar, M S

    2000-06-01

    More women than men eventually develop hypertension in the United States due to their higher numbers and longer longevity. The white coat hypertension is also more common in women. Alcohol, obesity and oral contraceptives are important causes of rise in blood pressure among women. On the other hand, hormone replacement therapy may decrease cardiovascular mortality in the postmenopausal woman. Women with left ventricular hypertrophy are at a greater risk of death than men. Fibromuscular hyperplasia and primary aldosteronism are more common as causes of secondary hypertension in women. Nonpharmacologic therapy, such as weight reduction, exercise, salt and alcohol reduction, should always be tried prior to medical treatment of hypertension and are very useful adjunctive measures in controlling hypertension. ACE inhibitors and angiotensin receptor blockers are contraindicated in pregnancy and should be avoided in women with childbearing potential. Hypertension remains a major public health problem among black women. Although the antihypertensive drug therapy seems to benefit white women the least, proportionately more of them comply with their antihypertensive therapy. Hypertension is the most common chronic medical condition requiring visits to the physicians, as well as prescription medications, in the United States. The epidemiology, clinical course, response to treatment and ultimate outcome of essential hypertension may vary with gender. More women than men eventually develop hypertension in the US due to their higher numbers and longer longevity. PMID:10927986

  7. Hypertensive emergencies in pregnancy.

    PubMed

    Vadhera, Rakesh B; Simon, Michelle

    2014-12-01

    Hypertensive disorders of pregnancy complicate 7% to 10% of pregnancies and are among the major causes of maternal and perinatal morbidity and mortality. Recently American College of Obstetricians and Gynecologists Taskforce on Hypertension during Pregnancy modified the diagnosis and management of hypertension in pregnancy, recommending prompt diagnosis, admission, close monitoring, and treatment. They strive to decrease maternal mortality and systemic complications. Labetalol, hydralazine, or nifedipine are considered first-line treatment, and either can be used to stabilize the patient with similar outcomes. Definite treatment is delivery of the fetus and should be considered based on the etiology of the hypertensive crisis and gestational age. PMID:25314092

  8. Hypertensive brain stem encephalopathy.

    PubMed

    Liao, Pen-Yuan; Lee, Chien-Chang; Chen, Cheng-Yu

    2015-01-01

    A 48-year-old man presented with headache and extreme hypertension. Computed tomography showed diffuse brain stem hypodensity. Magnetic resonance imaging revealed diffuse brain stem vasogenic edema. Hypertensive brain stem encephalopathy is an uncommon manifestation of hypertensive encephalopathy, which classically occurs at parietooccipital white matter. Because of its atypical location, the diagnosis can be challenging. Moreover, the coexistence of hypertension and brain stem edema could also direct clinicians toward a diagnosis of ischemic infarction, leading to a completely contradictory treatment goal. PMID:25082596

  9. HYPAZ: Hypertension Induced by Pazopanib

    ClinicalTrials.gov

    2015-07-18

    Renal Cell Carcinoma; Soft Tissue Sarcoma; Glioblastoma; Ovarian Cancer; Cervical Cancer; Breast Cancer; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Pancreatic Cancer; Melanoma; Gastrointestinal Cancer

  10. Stress and hypertension.

    PubMed

    Kulkarni, S; O'Farrell, I; Erasi, M; Kochar, M S

    1998-12-01

    Stress can cause hypertension through repeated blood pressure elevations as well as by stimulation of the nervous system to produce large amounts of vasoconstricting hormones that increase blood pressure. Factors affecting blood pressure through stress include white coat hypertension, job strain, race, social environment, and emotional distress. Furthermore, when one risk factor is coupled with other stress producing factors, the effect on blood pressure is multiplied. Overall, studies show that stress does not directly cause hypertension, but can have an effect on its development. A variety of non-pharmacologic treatments to manage stress have been found effective in reducing blood pressure and development of hypertension, examples of which are meditation, acupressure, biofeedback and music therapy. Recent results from the National Health and Nutrition Examination Survey indicate that 50 million American adults have hypertension (defined to be a systolic blood pressure of greater than 139 mm Hg or a diastolic blood pressure of greater than 89 mm Hg). In 95% of these cases, the cause of hypertension is unknown and they are categorized as "essential" hypertension. Although a single cause may not be identified, the general consensus is that various factors contribute to blood pressure elevation in essential hypertension. In these days of 70 hour work weeks, pagers, fax machines, and endless committee meetings, stress has become a prevalent part of people's lives; therefore the effect of stress on blood pressure is of increasing relevance and importance. Although stress may not directly cause hypertension, it can lead to repeated blood pressure elevations, which eventually may lead to hypertension. In this article we explore how stress can cause hypertension and what can be done about it. PMID:9894438

  11. Difference in effects of stretch on depressive effect of endothelium-derived nitric oxide on noradrenaline- and high-K+-induced contractions between the aortae from normotensive and spontaneously hypertensive rats.

    PubMed

    Sekiguchi, F; Miyake, Y; Nakazumi, S; Shimamura, K; Yamamoto, K; Sunano, S

    2001-02-01

    Difference in effects of stretch tension on endothelium-derived nitric oxide (EDNO)-dependent depression of noradrenaline (NA)- and high-K+-induced contraction between the aortae from normotensive Wistar Kyoto rats (WKY) a nd stroke-pronespontaneously hypertensive rats (SHRSP) was studied. NA-induced contraction in preparations both from WKY and SHRSP was augmented in the presence of N(omega)-nitro-L-arginine (L-NNA). This augmentation was minimized when the spontaneous tone, which was more prominent in preparations from SHRSP, was subtracted and the effects of L-NNA became less prominent in preparations from SHRSP. The effects of L-NNA were maximal at the stretch tension of 15 mN and, then, decreased as stretch tension increased in both preparations when the spontaneous tone was subtracted. The effects of L-NNA were less prominent when the contraction was initiated by high-K+, although the effects of stretch on high-K+-induced contraction were similar to that of NA-induced contraction. These results suggested 1) that both NA- and high-K+-induced contractions are depressed by EDNO, 2) that the release of EDNO induced by high-K+ is less than that by NA, 3) that increase in stretch tension decreases the release of EDNO, and 4) that the depressive effect of EDNO on contraction is impaired in the aorta of SHRSP. PMID:11436982

  12. Hormones and Hypertension

    MedlinePLUS

    ... and factors such as eating too much salt, obesity, and the use of tobacco, alcohol, and certain medications play a part. Hormones made in the kidneys and in blood vessels play a key role in the start and continuation of primary hypertension. Secondary hypertension is due to other diseases such ...

  13. Hypertension in the elderly

    PubMed Central

    Lionakis, Nikolaos; Mendrinos, Dimitrios; Sanidas, Elias; Favatas, Georgios; Georgopoulou, Maria

    2012-01-01

    The elderly are the most rapidly growing population group in the world. Data collected over a 30-year period have demonstrated the increasing prevalence of hypertension with age. The risk of coronary artery disease, stroke, congestive heart disease, chronic kidney insufficiency and dementia is also increased in this subgroup of hypertensives. Hypertension in the elderly patients represents a management dilemma to cardiovascular specialists and other practioners. During the last years and before the findings of the Systolic Hypertension in Europe Trial were published, the general medical opinion considered not to decrease blood pressure values similarly to other younger patients, in order to avoid possible ischemic events and poor oxygenation of the organs (brain, heart, kidney). The aim of this review article is to highlight the importance of treating hypertension in aged population in order to improve their quality of life and lower the incidence of the cardiovascular complications. PMID:22655162

  14. Valsartan regulates myocardial autophagy and mitochondrial turnover in experimental hypertension.

    PubMed

    Zhang, Xin; Li, Zi-Lun; Crane, John A; Jordan, Kyra L; Pawar, Aditya S; Textor, Stephen C; Lerman, Amir; Lerman, Lilach O

    2014-07-01

    Renovascular hypertension alters cardiac structure and function. Autophagy is activated during left ventricular hypertrophy and linked to adverse cardiac function. The angiotensin II receptor blocker, valsartan, lowers blood pressure and is cardioprotective, but whether it modulates autophagy in the myocardium is unclear. We hypothesized that valsartan would alleviate autophagy and improve left ventricular myocardial mitochondrial turnover in swine renovascular hypertension. Domestic pigs were randomized to control, unilateral renovascular hypertension, and renovascular hypertension treated with valsartan (320 mg/d) or conventional triple therapy (reserpine+hydralazine+hydrochlorothiazide) for 4 weeks after 6 weeks of renovascular hypertension (n=7 each group). Left ventricular remodeling, function, and myocardial oxygenation and microcirculation were assessed by multidetector computer tomography, blood oxygen level-dependent MRI, and microcomputer tomography. Myocardial autophagy, markers for mitochondrial degradation and biogenesis, and mitochondrial respiratory-chain proteins were examined ex vivo. Renovascular hypertension induced left ventricular hypertrophy and myocardial hypoxia, enhanced cellular autophagy and mitochondrial degradation, and suppressed mitochondrial biogenesis. Valsartan and triple therapy similarly decreased blood pressure, but valsartan solely alleviated left ventricular hypertrophy, ameliorated myocardial autophagy and mitophagy, and increased mitochondrial biogenesis. In contrast, triple therapy only slightly attenuated autophagy and preserved mitochondrial proteins, but elicited no improvement in mitophagy. These data suggest a novel potential role of valsartan in modulating myocardial autophagy and mitochondrial turnover in renovascular hypertension-induced hypertensive heart disease, which may possibly bolster cardiac repair via a blood pressure-independent manner. PMID:24752430

  15. [Resistant arterial hypertension].

    PubMed

    Bobrie, G; Coville, P

    1995-08-01

    The aim of the study was to determine the prevalence of resistant hypertension in our unit and the frequency of its various causes. Of the 890 patients seen for the first time between January 1, 1993, and June 30, 1994, 257 were referred for hypertension. Of the 62 (24.1%) patients referred for "resistant hypertension", only 25 met our criteria for resistance: blood pressure > or = 160 and/or 95 mmHg on the first visit to us without "white-coat" effect and at least two additive antihypertensive drugs at optimal doses. Of the 195 patients referred for other reasons, 10 met our criteria for resistance. Thus, the prevalence of resistant hypertension is 13.5%. A cause of resistant hypertension was found in 50% of the patients referred for resistant hypertension, in 72.2% of the patients who met our criteria for resistance and in 84% of the patients referred for resistant hypertension and who met our criteria for resistance. PMID:8572870

  16. Resistant hypertension - an update.

    PubMed

    Pasha, K; Towhiduzzaman, M; Manwar, A; Jahan, M U

    2015-04-01

    Patients with hypertension are increasing in Bangladesh. Among these patients a growing number of patients are having resistant hypertension faced by both primary care physicians and specialists. There is no data regarding prevalence of resistant hypertension in Bangladesh, but clinical trials abroad suggests that it is not rare, involving perhaps 20% to 30% of study participants. Cardiovascular risk is undoubtedly increased in such patients and the condition is often complicated by multiple other cardiovascular risk factors such as obesity, sleep apnea, diabetes, and chronic kidney disease. Resistant hypertension is almost always multifactorial in etiology. Successful treatment requires identification and reversal of lifestyle factors contributing to treatment resistance; diagnosis and appropriate treatment of secondary causes of hypertension; and use of effective multi drug regimens. Studies of resistant hypertension are limited by the high cardiovascular risk of patients within this subgroup, which generally precludes safe withdrawal of medications; presence of multiple disease processes and their associated medical therapies, which confound interpretation of study results. Therefore we should concentrate on expanding our knowledge of the causes of resistant hypertension which will allow for more effective prevention and/or treatment which is essential to improve long-term clinical management of this condition. PMID:26007281

  17. Susceptibility genes in hypertension.

    PubMed

    Armani, C; Botto, N; Andreassi, M G

    2011-01-01

    Hypertension is a complex, multifactorial disease; genetic factors represent one third to half of the inter-individual variability of blood pressure values. Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Recent advances in molecular biology have revealed the pathogenesis of hypertension in many of these conditions. Remarkably, the mechanism in every case has proved to be upregulation of sodium Na reabsorption in the distal nephron, with accompanying expansion of extracellular volume. On the contrary in the essential hypertension the underlying pathogenetic mechanism is more complex because of interplay between several 'risk' genes and environmental factors. It is assumed that blood pressure is under the control of a large number of genes each of which has only relatively mild effects. It has therefore been difficult to discover the genes that contribute to blood pressure variation using traditional approaches including candidate gene studies and linkage studies. Recent development of genotyping technology made large scale genome-wide association studies possible. This approach and the study of monogenic forms of hypertension has led to the discovery of novel and robust candidate genes for human essential hypertension, many of which require functional analysis in experimental models. This review summarizes the current findings for candidate genes associated with blood pressure and focuses on recent advances and future potential of pharmacogenetics of hypertension, with the intent to clarify what amount of these investments in basic science research will be delivered into benefits to patients. PMID:21861838

  18. Perioperative hypertension management

    PubMed Central

    Varon, Joseph; Marik, Paul E

    2008-01-01

    Perioperative hypertension is commonly encountered in patients that undergo surgery. While attempts have been made to standardize the method to characterize the intraoperative hemodynamics, these methods still vary widely. In addition, there is a lack of consensus concerning treatment thresholds and appropriate therapeutic targets, making absolute recommendations about treatment difficult. Nevertheless, perioperative hypertension requires careful management. When treatment is necessary, therapy should be individualized for the patient. This paper reviews the pharmacologic agents and strategies commonly used in the management of perioperative hypertension. PMID:18827911

  19. [Chronic thromboembolic pulmonary hypertension].

    PubMed

    Vavera, Zden?k

    2015-03-01

    In recent years, we have witnessed a growing interest in diseases of pulmonary circulation. It is due to the development of specific drug therapy for pulmonary hypertension (PH), improving the availability and performance of endarterectomy techniques of pulmonary artery. This technique has been established as method of choice for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, the crucial issue is early indication of treatment, right diagnosis and determination of exact type of pulmonary hypertension. Modern therapeutic approaches provide better prognosis, quality of life and even possibility to cure the patients, especially suffering from CTEPH. This article discusses the issue of CTEPH. PMID:25873119

  20. Orexin, cardio-respiratory function, and hypertension

    PubMed Central

    Li, Aihua; Nattie, Eugene

    2014-01-01

    In this review we focus on the role of orexin in cardio-respiratory functions and its potential link to hypertension. (1) Orexin, cardiovascular function, and hypertension. In normal rats, central administration of orexin can induce significant increases in arterial blood pressure (ABP) and sympathetic nerve activity (SNA), which can be blocked by orexin receptor antagonists. In spontaneously hypertensive rats (SHRs), antagonizing orexin receptors can significantly lower blood pressure under anesthetized or conscious conditions. (2) Orexin, respiratory function, and central chemoreception. The prepro-orexin knockout mouse has a significantly attenuated ventilatory CO2 chemoreflex, and in normal rats, central application of orexin stimulates breathing while blocking orexin receptors decreases the ventilatory CO2 chemoreflex. Interestingly, SHRs have a significantly increased ventilatory CO2 chemoreflex relative to normotensive WKY rats and blocking both orexin receptors can normalize this exaggerated response. (3) Orexin, central chemoreception, and hypertension. SHRs have higher ABP and SNA along with an enhanced ventilatory CO2 chemoreflex. Treating SHRs by blocking both orexin receptors with oral administration of an antagonist, almorexant (Almxt), can normalize the CO2 chemoreflex and significantly lower ABP and SNA. We interpret these results to suggest that the orexin system participates in the pathogenesis and maintenance of high blood pressure in SHRs, and the central chemoreflex may be a causal link to the increased SNA and ABP in SHRs. Modulation of the orexin system could be a potential target in treating some forms of hypertension. PMID:24574958

  1. A generalized physiological hyperreactivity to acute stressors in hypertensives.

    PubMed

    Nyklícek, Ivan; Bosch, Jos A; Amerongen, Arie V Nieuw

    2005-09-01

    Hypertensives have consistently been found to have a more reactive cardiovascular system than normotensives. In the present study, it was examined whether this enhanced cardiovascular stress reactivity generalizes to the hypothalamus-pituitary-adrenal (HPA) axis and the immune system. Forty-two unmedicated hypertensives and 21 normotensive controls performed five passive coping and active coping stressful tasks in the laboratory. In addition to the expected greater mean diastolic blood pressure reactivity to the tasks, hypertensives exhibited enhanced (baseline corrected) task salivary cortisol and secretory immunoglobulin A (S-IgA) levels. Moreover, correlations were found between blood pressure responses and task related cortisol activity and between baseline blood pressure levels and task-induced S-IgA levels. These results indicate that hypertensives not only have a hyperreactive cardiovascular system, but also an enhanced HPA axis and immune system reactivity to stress. A central stress mechanism may be responsible for the heightened generalized stress response in hypertensives. PMID:16038773

  2. High Blood Pressure (Hypertension)

    MedlinePLUS

    ... Page Text Size: A A A Listen High Blood Pressure (Hypertension) Nearly 1 in 3 American adults ... if your doctor prescribes it, medicine. What Is Blood Pressure? Blood pressure is the force of blood ...

  3. What Causes Pulmonary Hypertension?

    MedlinePLUS

    ... types of PH. Group 1 pulmonary arterial hypertension (PAH) may have no known cause, or the condition ... diseases and conditions also can cause group 1 PAH. Examples include HIV infection, congenital heart disease , and ...

  4. Hypertensive heart disease

    MedlinePLUS

    ... failure: pathophysiology and diagnosis. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... Victor RG. Arterial hypertension. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  5. Pharmacotherapy of Pulmonary Hypertension

    PubMed Central

    Steinhorn, Robin H.

    2012-01-01

    Pulmonary arterial hypertension is a serious disease with significant morbidity and mortality. While it can occur idiopathically, it is more commonly associated with other cardiac or lung diseases. While most of the available therapies were tested in adult populations, and most therapies in children remain off-label, new reports and randomized trials are emerging that inform the treatment of pediatric populations. This review discusses currently available therapies for pediatric pulmonary hypertension, their biologic rationales, and evidence for their clinical effectiveness. PMID:23036248

  6. Diastolic function in hypertension

    Microsoft Academic Search

    Robert A. Phillips; Joseph A. Diamond

    2001-01-01

    Diastolic dysfunction in patients with hypertension may present as asymptomatic findings on noninvasive testing, or as fulminant\\u000a pulmonary edema, despite normal left ventricular systolic function. Up to 40% of hypertensive patients presenting with clinical\\u000a signs of congestive heart failure have normal systolic left ventricular function. In this article we review the pathophysiologic\\u000a factors affecting diastolic function in individuals with diastolic

  7. Chronic Thromboembolic Pulmonary Hypertension

    Microsoft Academic Search

    William R. Auger; Peter F. Fedullo

    Chronic thromboembolic pulmonary hypertension (CTEPH) is an important form of pulmonary hypertension to detect because prompt\\u000a treatment can lead to a surgical cure. The true incidence is unknown, but it is estimated to occur in 1% to 3% of patients\\u000a following acute thromboembolism. Detection may be difficult, because symptoms are nonspecific and other diagnoses are often\\u000a made before that of

  8. Chronic thromboembolic pulmonary hypertension

    Microsoft Academic Search

    P. Dartevelle; E. Fadel; S. Mussot; A. Chapelier; P. Herve; M. de Perrot; J. Cerrina; F. L. Ladurie; D. Lehouerou; M. Humbert; O. Sitbon; G. Simonneau

    2004-01-01

    ABSTRACT: Pulmonary arterial hypertension is a severe disease that has been ignored for a long time. However, over the past 20 yrs chest physicians, cardiologists and thoracic,surgeons,have,shown,increasing interest in this disease because,of the development of new therapies, that have improved both the outcome and quality of life of patients, including pulmonary transplantation and prostacyclin therapy. Chronic thromboembolic,pulmonary,arterial hypertension,(CTEPH) can be

  9. Management: Cirrhotic Portal Hypertension

    Microsoft Academic Search

    Joseph K. Lim; Guadalupe Garcia-Tsao

    \\u000a Gastroesophageal varices are a direct consequence of portal hypertension, the main complication of cirrhosis. An understanding\\u000a of the pathophysio­logy of portal hypertension has led to significant improvements in the prevention and treatment of variceal\\u000a hemorrhage. However, variceal hemorrhage continues to carry a significant mortality. By screening all patients with cirrhosis\\u000a for varices, applying prophylaxis appropriately, actively managing acute variceal hemorrhage,

  10. Early co-expression of cyclooxygenase-2 and renin in the rat kidney cortex contributes to the development of N(G)-nitro-L-arginine methyl ester induced hypertension.

    PubMed

    Guzmán-Hernández, Elizabeth Alejandrina; Villalobos-Molina, Rafael; Sánchez-Mendoza, María Alicia; Del Valle-Mondragón, Leonardo; Pastelín-Hernández, Gustavo; Ibarra-Barajas, Maximiliano

    2015-04-01

    We investigated the involvement of cyclooxygenase-2 (COX-2) and the renin-angiotensin system in N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Male Wistar rats were treated with L-NAME (75.0 mg·(kg body mass)(-1)·day(-1), in their drinking water) for different durations (1-33 days). COX-2 and renin mRNA were measured using real-time PCR in the renal cortex, and prostanoids were assessed in the renal perfusate, whereas angiotensin II (Ang?II) and Ang?(1-7) were quantified in plasma. In some rats, nitric oxide synthase inhibition was carried out in conjunction with oral administration of captopril (30.0 mg·kg(-1)·day(-1)) or celecoxib (1.0 mg·kg(-1)·day(-1)) for 2 or 19 days. We found a parallel increase in renocortical COX-2 and renin mRNA starting at day 2 of treatment with L-NAME, and both peaked at 19-25 days. In addition, L-NAME increased renal 6-Keto-PGF(1?) (prostacyclin (PGI2) metabolite) and plasma Ang?II from day 2, but reduced plasma Ang?(1-7) at day 19. Captopril prevented the increase in blood pressure, which was associated with lower plasma Ang?II and increased COX-2-derived 6-Keto-PGF(1?) at day 2 and plasma Ang?(1-7) at day 19. Celecoxib partially prevented the increase in blood pressure; this effect was associated with a reduction in plasma Ang?II. These findings indicate that renal COX-2 expression increased in parallel with renin expression, renal PGI2 synthesis, and plasma Ang?II in L-NAME-induced hypertension. PMID:25761067

  11. Resistant hypertension and chronotherapy.

    PubMed

    Prkacin, Ingrid; Balenovic, Diana; Djermanovic-Dobrota, Vesna; Lukac, Iva; Drazic, Petra; Pranjic, Iva-Klara

    2015-04-01

    Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing's syndrome, thyroid diseases, aortic coarctation. For diagnosing patient's history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of "non-dipper" hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures. PMID:26005390

  12. Amlodipine-induced reduction of oxidative stress in the brain is associated with sympatho-inhibitory effects in stroke-prone spontaneously hypertensive rats.

    PubMed

    Hirooka, Yoshitaka; Kimura, Yoshikuni; Nozoe, Masatsugu; Sagara, Yoji; Ito, Koji; Sunagawa, Kenji

    2006-01-01

    Amlodipine is a dihydropyridine calcium channel blocker that is widely used for the treatment of hypertensive patients and has an antioxidant effect on vessels in vitro. The aim of the present study was to examine whether treatment with amlodipine reduced oxidative stress in the brains of stroke-prone spontaneously hypertensive rats (SHRSP). The animals received amlodipine, nicardipine or hydralazine for 30 days in their drinking water. Levels of thiobarbituric acid-reactive substances (TBARS) in the brain (cortex, cerebellum, hypothalamus, and brainstem) were measured before and after each treatment. Systolic blood pressure decreased to similar levels in the amlodipine-, nicardipine-, and hydralazine-treated groups. Urinary norepinephrine excretion was significantly reduced in SHRSP after treatment with amlodipine, but not with nicardipine or hydralazine. Levels of TBARS in the cortex, cerebellum, hypothalamus, and brainstem were significantly higher in SHRSP than in Wistar-Kyoto rats (WKY), and were reduced in amlodipine-treated, but not in nicardipine- or hydralazine-treated, SHRSP. Electron spin resonance spectroscopy revealed increased levels of reactive oxygen species in the brains of SHRSP, which were reduced by treatment with amlodipine. Intracisternal infusion of amlodipine also reduced systolic blood pressure, urinary norepinephrine excretion, and the levels of TBARS in the brain. These results suggested that oxidative stress in the brain was enhanced in SHRSP compared with WKY rats. In addition, antihypertensive treatment with amlodipine reduced oxidative stress in all areas of the brain examined and decreased blood pressure without a reflex increase in sympathetic nerve activity in SHRSP. PMID:16715653

  13. Superoxide dismustase mimetic tempol decreases blood pressure by increasing renal medullary blood flow in hyperinsulinemic-hypertensive rats

    Microsoft Academic Search

    Shizuka Onuma; Kazushige Nakanishi

    2004-01-01

    Insulin resistance and compensatory hyperinsulinemia often coexist in hypertensive patients, which may play a role in the development of hypertension. Because medullary blood flow (MBF), which is strongly influenced by the nitric oxide (NO) system, is thought to be an important component of blood pressure and sodium balance, we focused particularly on MBF in fructose-induced hypertensive rats. Moreover, it has

  14. [Sodium and hypertension].

    PubMed

    de Wardener, H E

    1996-09-01

    Over several million years the human race was programmed to eat a diet which contained about 15 mmol of sodium (1 g of sodium chloride) per day. It is only five to ten thousand years ago that we became addicted to salt. Today we eat about 150 mmol of sodium (9-12 g of salt) per day. It is now apparent that this sudden rise in sodium intake (in evolutionary terms) is the most likely cause for the rise in blood pressure with age that occurs in the majority of the world's population. Those which consume less than 60 mmol/day do not develop hypertension. The reason for the rise in sodium intake is not known but it is probable that an important stimulus was the discovery that meat could be preserved by immersion into a concentrated salt solution. This seemingly miraculous power endowed salt with such magical and medicinal qualities that it became a symbol of goodness and health. It was not until 1904 Ambard and Beaujard suggested that on the contrary dietary salt could be harmful and raise the blood pressure. At first the idea did not prosper and it continues to be opposed by a diminishing band. The accumulated evidence that sodium intake is related to the blood pressure in normal man and animals and in inherited forms of hypertension has been obtained from experimental manipulations and studies of human populations. The following observation links sodium and hypertension. An increase in sodium intakes raises the blood pressure of the normal rat, dog, rabbit, baboon, chimpanzee and man. Population studies have demonstrated a significant correlation between sodium intake and the customary rise in blood pressure with age. The development of hypertensive strains of rats has revealed that the primary genetic lesion which gives rise to hypertension resides in the kidney where it impairs the urinary excretion of sodium. There is similar but less convincing evidence in essential hypertension. The kidney in both essential hypertension and hypertensive strains of rats share a number of functional abnormalities most of which are capable of impairing sodium excretion. Essential hypertension would appear to be as much a renal disturbance related to the intake of sodium as hypertension secondary to renal disease. PMID:8952809

  15. Pulmonary arterial hypertension in pregnancy.

    PubMed

    Obi?an, Sarah G; Cleary, Kirsten L

    2014-08-01

    Pulmonary hypertension is a medical condition characterized by elevated pulmonary arterial pressure and secondary right heart failure. Pulmonary arterial hypertension is a subset of pulmonary hypertension, which is characterized by an underlying disorder of the pulmonary arterial vasculature. Pulmonary hypertension can also occur secondarily to structural cardiac disease, autoimmune disorders, and toxic exposures. Although pregnancies affected by pulmonary hypertension and pulmonary arterial hypertension are rare, the pathophysiology exacerbated by pregnancy confers both high maternal and fetal mortality and morbidity. In light of new treatment modalities and the use of a multidisciplinary approach to care, maternal outcomes may be improving. PMID:25037519

  16. A Blueberry-Enriched Diet Attenuates Nephropathy in a Rat Model of Hypertension via Reduction in Oxidative Stress

    Microsoft Academic Search

    Carrie M. Elks; Scott D. Reed; Nithya Mariappan; Barbara Shukitt-Hale; James A. Joseph; Donald K. Ingram; Joseph Francis; Carmine Zoccali

    2011-01-01

    Objective and BackgroundTo assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Oxidative stress (OS) appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-induced renal injury; however, attention has shifted recently to the therapeutic potential of natural products as antioxidants. Blueberries (BB) have among the

  17. Protective actions of nebivolol on chronic nitric oxide synthase inhibition-induced hypertension and chronic kidney disease in the rat: a comparison with angiotensin II receptor blockade

    PubMed Central

    Tsarova, Tatsiana; Sasser, Jennifer M.; Baylis, Chris

    2012-01-01

    Background. Nitric oxide (NO) deficiency contributes to chronic kidney disease (CKD) progression and hypertension. The ?-blocker, nebivolol (N), also enhances NO production, and we studied whether N attenuates CKD and hypertension caused by chronic NO synthase inhibition (CNOSI). Methods. Male Sprague–Dawley rats on 6 weeks of CNOSI (L-NAME, 150 mg/L drinking water) received placebo (P), N (10 mg/kg/day), olmesartan (O, 2.5 mg/kg/day) or N + O. Blood pressure (BP) and urine protein and NOx (metabolites of NO) were monitored throughout. We measured glomerular sclerosis (GS), creatinine clearance (CCr) and components of the NO and oxidant pathways in the renal cortex. Results. BP increased >50 mmHg in P by weeks 4–6, but no change occurred in N, O or N + O. P rats developed proteinuria and GS and CCr was ?30% of normal. In N, O and N + O, all values remained normal. In renal cortex of P, p22phox and nitrotyrosine abundance as well as H2O2 levels were higher and extracellular superoxide dismutase (EC SOD) was lower versus normal kidneys. N, O and N + O normalized p22phox, H2O2 and EC SOD and increased Mn SOD above normal. The cortical neuronal NO synthase (nNOS) ? abundance increased in P and this was prevented by N, O and N + O. Conclusion. We suggest that the major benefit from both N and O is reduction in oxidative stress in the renal cortex, which may potentiate residual local NO. There was no additive benefit of N + O since each drug effectively prevented injury, but a combination may be beneficial where protection is incomplete with each drug. The increased nNOS? protein seen early in the course of the CKD may contribute to the evolving GS. PMID:21856762

  18. Masked hypertension and hidden uncontrolled hypertension after renal transplantation

    Microsoft Academic Search

    Dusan Paripovic; Mirjana Kostic; Brankica Spasojevic; Divna Kruscic; Amira Peco-Antic

    2010-01-01

    Arterial hypertension is a risk factor affecting graft function in pediatric kidney transplants. Recent pediatric studies\\u000a reported a high prevalence of hypertension, especially nocturnal hypertension in this population. Data regarding the prevalence\\u000a of masked hypertension in pediatric patients with kidney transplants are still scarce. The aim of this cross-sectional study\\u000a was to assess the prevalence of masked and hidden uncontrolled

  19. Pregnancy with Portal Hypertension

    PubMed Central

    Aggarwal, Neelam; Negi, Neha; Aggarwal, Aakash; Bodh, Vijay; Dhiman, Radha K.

    2014-01-01

    Even though pregnancy is rare with cirrhosis and advanced liver disease, but it may co-exist in the setting of non-cirrhotic portal hypertension as liver function is preserved but whenever encountered together is a complex clinical dilemma. Pregnancy in a patient with portal hypertension presents a special challenge to the obstetrician as so-called physiological hemodynamic changes associated with pregnancy, needed for meeting demands of the growing fetus, worsen the portal hypertension thereby putting mother at risk of potentially life-threatening complications like variceal hemorrhage. Risks of variceal bleed and hepatic decompensation increase many fold during pregnancy. Optimal management revolves round managing the portal hypertension and its complications. Thus management of such cases requires multi-speciality approach involving obstetricians experienced in dealing with high risk cases, hepatologists, anesthetists and neonatologists. With advancement in medical field, pregnancy is not contra-indicated in these women, as was previously believed. This article focuses on the different aspects of pregnancy with portal hypertension with special emphasis on specific cause wise treatment options to decrease the variceal bleed and hepatic decompensation. Based on extensive review of literature, management from pre-conceptional period to postpartum is outlined in order to have optimal maternal and perinatal outcomes. PMID:25755552

  20. How Is Pulmonary Hypertension Treated?

    MedlinePLUS

    ... Pulmonary Arterial Hypertension Group 1 pulmonary arterial hypertension (PAH) includes PH that's inherited, that has no known ... certain drugs or conditions. Treatments for group 1 PAH include medicines and medical procedures. Medicines Your doctor ...

  1. Stress and hypertension.

    PubMed Central

    Mustacchi, P.

    1990-01-01

    In susceptible persons emotional stress results in immediate sympathetic stimulation, with a vasomotor response that results in a high-output state and elevated blood pressure; the vasopressor response seems to be transient. There seems to be no longitudinal epidemiologic validation of the attractive hypothesis that transiently elevated blood pressures are the prelude to fixed hypertension, however. The acquisition of hypertension by populations abandoning their traditional mode of living has been attributed to the sociocultural stress inherent in westernization, but these studies usually have not taken into account concomitants of this type of acculturation, such as dietary changes and increased body weight. The inverse relationship of blood pressure levels to education could explain the development of hypertension when aspiration to upward mobility is thwarted. The severity of perceived occupational stress relates inversely to blood pressure, suggesting that familiarity with a job renders the demands made by the work environment more predictable and less threatening in terms of vasopressor response. PMID:2219875

  2. Oxidative stress and hypertension.

    PubMed

    Harrison, David G; Gongora, Maria Carolina

    2009-05-01

    This review has summarized some of the data supporting a role of ROS and oxidant stress in the genesis of hypertension. There is evidence that hypertensive stimuli, such as high salt and angiotensin II, promote the production of ROS in the brain, the kidney, and the vasculature and that each of these sites contributes either to hypertension or to the untoward sequelae of this disease. Although the NADPH oxidase in these various organs is a predominant source, other enzymes likely contribute to ROS production and signaling in these tissues. A major clinical challenge is that the routinely used antioxidants are ineffective in preventing or treating cardiovascular disease and hypertension. This is likely because these drugs are either ineffective or act in a non-targeted fashion, such that they remove not only injurious ROS Fig. 5. Proposed role of T cells in the genesis of hypertension and the role of the NADPH oxidase in multiple cells/organs in modulating this effect. In this scenario, angiotensin II stimulates an NADPH oxidase in the CVOs of the brain, increasing sympathetic outflow. Sympathetic nerve terminals in lymph nodes activate T cells, and angiotensin II also directly activates T cells. These stimuli also activate expression of homing signals in the vessel and likely the kidney, which attract T cells to these organs. T cells release cytokines that stimulate the vessel and kidney NADPH oxidases, promoting vasoconstriction and sodium retention. SFO, subfornical organ. 630 Harrison & Gongora but also those involved in normal cell signaling. A potentially important and relatively new direction is the concept that inflammatory cells such as T cells contribute to hypertension. Future studies are needed to understand the interaction of T cells with the CNS, the kidney, and the vasculature and how this might be interrupted to provide therapeutic benefit. PMID:19427495

  3. Dietary Chloride as a Determinant of ``Sodium-Dependent'' Hypertension

    Microsoft Academic Search

    Theodore W. Kurtz; R. Curtis Morris

    1983-01-01

    The uninephrectomized rat given desoxycorticosterone (DOC) provides a classic model of ``sodium-dependent'' hypertension. In such rats, the extent to which a given dietary intake of sodium induced an increase in blood pressure depended on whether or not the anionic component of the sdoium salt was chloride. With normal and high dietary intakes of sodium, sodium chloride induced increases in blood

  4. Atrial Arrhythmia in Ageing Spontaneously Hypertensive Rats: Unraveling the Substrate in Hypertension and Ageing

    PubMed Central

    Lau, Dennis H.; Shipp, Nicholas J.; Kelly, Darren J.; Thanigaimani, Shivshankar; Neo, Melissa; Kuklik, Pawel; Lim, Han S.; Zhang, Yuan; Drury, Karen; Wong, Christopher X.; Chia, Nicholas H.; Brooks, Anthony G.; Dimitri, Hany; Saint, David A.; Brown, Lindsay; Sanders, Prashanthan

    2013-01-01

    Background Both ageing and hypertension are known risk factors for atrial fibrillation (AF) although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR). Methods SHR were studied at 12 and 15 months of age (n?=?8 per group) together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY). Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP), atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis. Results Compared to WKY controls, the SHR demonstrated: Higher systolic blood pressure (p<0.0001), bi-atrial enlargement (p<0.05), bi-ventricular hypertrophy (p<0.05), lower atrial ERP (p?=?0.008), increased atrial conduction heterogeneity (p?=?0.001) and increased atrial interstitial fibrosis (p?=?0.006) & CD68-positive macrophages infiltration (p<0.0001). These changes resulted in higher atrial arrhythmia inducibility (p?=?0.01) and longer induced AF episodes (p?=?0.02) in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01) and atrial conduction heterogeneity (p<0.01) without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages. Conclusions Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria. PMID:24013508

  5. Mineralocorticoid actions in the brain and hypertension.

    PubMed

    Huang, Bing S; Leenen, Frans H H

    2011-06-01

    Mineralocorticoid receptors (MR) and epithelial sodium channels (ENaC) in the brain mediate central aldosterone-induced sympathetic hyperactivity and hypertension. Enzymes for biosynthesis of aldosterone are present in the brain, and aldosterone can be produced locally in the brain. Hypothalamic aldosterone levels increase in Dahl salt-sensitive rats on high-salt diet, and in Wistar rats with chronic central infusion of sodium-rich artificial cerebrospinal fluid (CSF) or with subcutaneous infusion of angiotensin II. Functional studies using antagonists of MR, ENaC, and ouabain-like compounds ("ouabain"), as well as specific aldosterone synthase inhibitors, suggest that an increase in local synthesis of aldosterone via MR and ENaC in the brain increases "ouabain" and thereby causes enhanced AT(1) receptor stimulation, leading to sympathoexcitation and hypertension. An increase in CSF sodium or an increase in angiotensinergic output from circumventricular organs such as the subfornical organ projecting to hypothalamic nuclei may increase local production of aldosterone and "ouabain" in magnocellular neurons in the supraoptic nucleus and paraventricular nucleus. This aldosterone-"ouabain" neuromodulatory mechanism appears to play a major role in salt-induced or angiotensin II-induced hypertension. PMID:21298576

  6. Oxidative stress and hypertension: Possibility of hypertension therapy with antioxidants

    PubMed Central

    Baradaran, Azar; Nasri, Hamid; Rafieian-Kopaei, Mahmoud

    2014-01-01

    Hypertension is a major risk factor for myocardial infarction, heart failure, stroke, peripheral arterial disease, and aortic aneurysm, and is a cause of chronic kidney disease. Hypertension is often associated with metabolic abnormalities such as diabetes and dyslipidemia, and the rate of these diseases is increasing nowadays. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of hypertension. A reduction in superoxide dismutase and glutathione peroxidase activity has been observed in newly diagnosed and untreated hypertensive subjects, which are inversely correlated with blood pressure. Hydrogen peroxide production is also higher in hypertensive subjects. Furthermore, hypertensive patients have higher lipid hydroperoxide production. Oxidative stress is also markedly increased in hypertensive patients with renovascular disease. If oxidative stress is indeed a cause of hypertension, then, antioxidants should have beneficial effects on hypertension control and reduction of oxidative damage should result in a reduction in blood pressure. Although dietary antioxidants may have beneficial effects on hypertension and cardiovascular risk factors, however, antioxidant supplementation has not been shown consistently to be effective and improvement is not usually seen in blood pressure after treatment with single or combination antioxidant therapy in subjects thought to be at high risk of cardiovascular disease. This matter is the main focus of this paper. A list of medicinal plants that have been reported to be effective in hypertension is also presented. PMID:25097610

  7. Pulmonary hypertension caused by pulmonary venous hypertension

    PubMed Central

    2014-01-01

    Abstract The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is extraordinarily variable, ranging from no impact on pulmonary vascular resistance (PVR) to a marked increase. The reasons for this are unknown. Both acutely reversible pulmonary vasoconstriction and pathological remodeling (especially medial hypertrophy and intimal hyperplasia) account for increased PVR when present. The mechanisms involved in vasoconstriction and remodeling are not clearly defined, but increased wall stress, especially in small pulmonary arteries, presumably plays an important role. Myogenic contraction may account for increased vascular tone and also indirectly stimulate remodeling of the vessel wall. Increased wall stress may also directly cause smooth muscle growth, migration, and intimal hyperplasia. Even long-standing and severe pulmonary hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an important clinical problem, especially because PVH due to left ventricular noncompliance lacks definitive therapy. The role of targeted PH therapy in patients with PVH-PH is unclear at this time. Most prospective studies indicate that these medications are not helpful or worse, but there is ample reason to think that a subset of patients with PVH-PH may benefit from phosphodiesterase inhibitors or other agents. A different approach to evaluating possible pharmacologic therapy for PVH-PH may be required to better define its possible utility. PMID:25610595

  8. UNILATERAL RENAL DISEASE AND HYPERTENSION

    PubMed Central

    Burns, Edgar

    1953-01-01

    Cure is obtained in about 20 per cent of patients with unilateral renal disease and hypertension who have nephrectomy primarily for relief of hypertension. Carrying out urologic studies on a larger number of hypertensive patients might result in tracing the condition to renal disease in more cases. Renal angiography more accurately indicates renal origin of hypertension than any other diagnostic study. When it can reasonably be established that hypertension is of renal origin, nephrectomy should be performed unless there is some general contraindication to an operative procedure. PMID:13106723

  9. Top-Down Lipidomics Reveals Ether Lipid Deficiency in Blood Plasma of Hypertensive Patients

    Microsoft Academic Search

    Juergen Graessler; Dominik Schwudke; Peter E. H. Schwarz; Ronny Herzog; Andrej Shevchenko; Stefan R. Bornstein; Jose A. L. Calbet

    2009-01-01

    BackgroundDyslipoproteinemia, obesity and insulin resistance are integrative constituents of the metabolic syndrome and are major risk factors for hypertension. The objective of this study was to determine whether hypertension specifically affects the plasma lipidome independently and differently from the effects induced by obesity and insulin resistance.Methodology\\/Principal FindingsWe screened the plasma lipidome of 19 men with hypertension and 51 normotensive male

  10. Kidney and hypertension

    Microsoft Academic Search

    Marcin Adamczak; Martin Zeier; Ralf Dikow; Eberhard Ritz

    2002-01-01

    Kidney and hypertension. There is a unique relationship between the kidney and blood pressure (BP): on the one hand, renal dysfunction and particularly renal disease cause an increase in BP, while on the other hand, high BP accelerates loss of function of the diseased kidney. Transplantation studies, both in experimental animals and humans, documented that “blood pressure goes with the

  11. Chronic thromboembolic pulmonary hypertension.

    PubMed

    Wittine, Lara M; Auger, William R

    2010-04-01

    The pulmonary hypertension (PH) and right heart dysfunction that results from chronic thromboembolic involvement of the pulmonary vascular bed is potentially curable with surgical endarterectomy. Over the past several decades, growing clinical experience has brought about increased recognition of this treatable form of PH. Moreover, advances in cardiothoracic surgical techniques have given an increasing number of patients with chronic thromboembolic PH (CTEPH) a surgical remedy with decreasing perioperative morbidity and mortality risks. The availability of pulmonary hypertensive-specific medical therapy for CTEPH patients with surgically inaccessible disease also has been a positive therapeutic advance over the past several years. However, despite this progress, chronic thromboembolic disease as a sequela of acute pulmonary emboli continues to be underappreciated. Furthermore, even if CTEPH has been appropriately diagnosed, misinterpretation of diagnostic information may lead to the inappropriate exclusion of patients from surgical consideration. This may result in the prescription of pulmonary hypertensive medical therapy in CTEPH patients with potentially surgically correctable disease. This difficulty arises from a lack of objective criteria as to what constitutes surgical chronic thromboembolic disease, which primarily is a result of the variability in surgical experience in specialty centers in the United States. Consequently, clinicians must be wary about using pulmonary hypertensive medications in CTEPH patients. Before prescription, it is important to exclude patients from surgical consideration by consulting a specialized center with expertise in this discipline. PMID:20376164

  12. Hypertension in pregnancy

    Microsoft Academic Search

    Richard Hayman

    2004-01-01

    A diagnosis of hypertension may be made in 5–8% of all pregnancies. Pre-eclampsia, a disease associated with defective placentation, is arguably the most important cause of maternal and fetal morbidity and mortality associated with a rise in maternal blood pressure. This clinical syndrome has a complex aetiology and pathophysiology, and is possibly the result of an as yet unidentified circulating

  13. Aldosterone and arterial hypertension

    Microsoft Academic Search

    Stefan Pilz; Eberhard Ritz; Barbara Obermayer-Pietsch; Thomas R. Pieber; Andreas Tomaschitz

    2009-01-01

    In the setting of primary aldosteronism, elevated aldosterone levels are associated with increased blood pressure. Aldosterone concentrations within the normal range, however, can also alter blood pressure. Furthermore, the aldosterone-to-renin ratio, an indicator of aldosterone excess, is associated with hypertension, even in patients without excessive absolute aldosterone levels. In this Review we assess the data on the role of aldosterone

  14. Chronic thromboembolic pulmonary hypertension.

    PubMed

    Kim, Nick H; Delcroix, Marion; Jenkins, David P; Channick, Richard; Dartevelle, Philippe; Jansa, Pavel; Lang, Irene; Madani, Michael M; Ogino, Hitoshi; Pengo, Vittorio; Mayer, Eckhard

    2013-12-24

    Since the last World Symposium on Pulmonary Hypertension in 2008, we have witnessed numerous and exciting developments in chronic thromboembolic pulmonary hypertension (CTEPH). Emerging clinical data and advances in technology have led to reinforcing and updated guidance on diagnostic approaches to pulmonary hypertension, guidelines that we hope will lead to better recognition and more timely diagnosis of CTEPH. We have new data on treatment practices across international boundaries as well as long-term outcomes for CTEPH patients treated with or without pulmonary endarterectomy. Furthermore, we have expanded data on alternative treatment options for select CTEPH patients, including data from multiple clinical trials of medical therapy, including 1 recent pivotal trial, and compelling case series of percutaneous pulmonary angioplasty. Lastly, we have garnered more experience, and on a larger international scale, with pulmonary endarterectomy, which is the treatment of choice for operable CTEPH. This report overviews and highlights these important interval developments as deliberated among our task force of CTEPH experts and presented at the 2013 World Symposium on Pulmonary Hypertension in Nice, France. PMID:24355646

  15. [Chronic thromboembolic pulmonary hypertension].

    PubMed

    Kim, Nick H; Delcroix, Marion; Jenkins, David P; Channick, Richard; Dartevelle, Philippe; Jansa, Pavel; Lang, Irene; Madani, Michael M; Ogino, Hitoshi; Pengo, Vittorio; Mayer, Eckhard

    2014-10-01

    Since the last World Symposium on Pulmonary Hypertension in 2008, we have witnessed numerous and exciting developments in chronic thromboembolic pulmonary hypertension (CTEPH). Emerging clinical data and advances in technology have led to reinforcing and updated guidance on diagnostic approaches to pulmonary hypertension, guidelines that we hope will lead to better recognition and more timely diagnosis of CTEPH. We have new data on treatment practices across international boundaries as well as long-term outcomes for CTEPH patients treated with or without pulmonary endarterectomy. Furthermore, we have expanded data on alternative treatment options for select CTEPH patients, including data from multiple clinical trials of medical therapy, including 1 recent pivotal trial, and compelling case series of percutaneous pulmonary angioplasty. Lastly, we have garnered more experience, and on a larger international scale, with pulmonary endarterectomy, which is the treatment of choice for operable CTEPH. This report overviews and highlights these important interval developments as deliberated among our task force of CTEPH experts and presented at the 2013 World Symposium on Pulmonary Hypertension in Nice, France. (J Am Coil Cardiol 2013;62:D92-9) ©2013 by the American College of Cardiology Foundation. PMID:25697039

  16. Paranormal healing and hypertension

    Microsoft Academic Search

    Jaap J Beutler; Johannes T M Attevelt; Sybo A Schouten; Joop A J Faber; Evert J Dorhout Mees; Gijsbert G Geijskes

    1988-01-01

    A prospective randomised trial was carried out to see whether paranormal healing by laying on of hands might reduce blood pressure in essential hypertension and whether such an effect might be due to a paranormal, psychological, or placebo factor. Patients were randomised to three treatment groups: paranormal healing by laying on of hands (n=40), paranormal healing at a distance (n=37),

  17. Airways Hyperresponsiveness Following a Single Inhalation Exposure to Doxorubicin-Induced Heart Failure Prevents Airways Transition Metal-Rich Particulate Matter in Hypertensive Rats

    EPA Science Inventory

    Exposure to particulate matter (PM) air pollution results in airways hyperresponsiveness (AHR), however it also results in adverse cardiovascular effects, particularly in individuals with underlying cardiovascular disease. The impact of pre-existing cardiac deficit on PM-induced ...

  18. Effects of Captopril on the Renin Angiotensin System, Oxidative Stress, and Endothelin in Normal and Hypertensive Rats

    PubMed Central

    Bolterman, Rodney J.; Manriquez, Melissa C.; Ruiz, M. Clara Ortiz; Juncos, Luis A.; Romero, J. Carlos

    2006-01-01

    There is substantial evidence suggesting that angiotensin II plays an important role in elevating blood pressure of spontaneously hypertensive rats, despite normal plasma renin activity, and that converting enzyme inhibitors (captopril) can effectively normalize blood pressure in the spontaneously hypertensive rats. One mechanism by which angiotensin II induces hypertension is via oxidative stress and endothelin, as seen in subpressor angiotensin II—induced hypertension. In fact, it has been shown that antioxidants lower mean arterial pressure in spontaneously hypertensive rats. However, the relationship between angiotensin II, oxidative stress, and endothelin in the spontaneously hypertensive rats is still relatively undefined. This study examines the relationship between mean arterial pressure, plasma renin activity, angiotensin II, oxidative stress, and endothelin in spontaneously hypertensive rats compared with normotensive Wistar Kyoto rats, and the effects of captopril on this association. Untreated spontaneously hypertensive rats had increased plasma angiotensin II levels despite normal plasma renin activity, oxidative stress, and endothelin. Captopril treatment in spontaneously hypertensive rats lowered mean arterial pressure, angiotensin II, oxidative stress, and endothelin, and increased plasma renin activity. In contrast, captopril increased plasma renin activity (suggesting effective captopril treatment) but did not significantly alter mean arterial pressure, angiotensin II, oxidative stress, or endothelin of Wistar Kyoto rats. These results suggest that in spontaneously hypertensive rats, angiotensin II is a primary instigator of hypertension, and that captopril selectively lowers angiotensin II, oxidant stress, and endothelin, which in turn may contribute to the blood pressure-lowering efficacy of captopril in spontaneously hypertensive rats. PMID:16087785

  19. Calcium Channel Blockades Exhibit Anti-Inflammatory and Antioxidative Effects by Augmentation of Endothelial Nitric Oxide Synthase and the Inhibition of Angiotensin Converting Enzyme in the NG-Nitro-L-Arginine Methyl Ester-Induced Hypertensive Rat Aorta: Vasoprotective Effects beyond the Blood Pressure-Lowering Effects of Amlodipine and Manidipine

    Microsoft Academic Search

    Hiroe Toba; Yoshitsugu Nakagawa; Shunsuke Miki; Takahiro Shimizu; Akiko Yoshimura; Riyako Inoue; Jun Asayama; Miyuki Kobara; Tetsuo Nakata

    2005-01-01

    Long-acting dihydropyridine calcium channel blockades have been shown to limit the progression of atherosclerosis and decrease the incidence of cardiovascular events in humans and animals. To investigate the vasoprotective effects beyond the blood pressure-lowering effects of these agents, amlodipine (20 mg\\/kg\\/day) and manidipine (10 mg\\/kg\\/day) were administered by gavage to NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats for 2 weeks. L-NAME

  20. Natriuretic peptides buffer renin-dependent hypertension.

    PubMed

    Demerath, Theo; Staffel, Janina; Schreiber, Andrea; Valletta, Daniela; Schweda, Frank

    2014-06-15

    The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP(-/-)) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP(-/-) mice were hypertensive and had reduced PRC compared with that in wild-type ANP(+/+) mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP(-/-) mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A(-/-) mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A(+/+) mice. However, the higher blood pressure in GC-A(-/-) mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A(-/-) mice than in GC-A(+/+) mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II. PMID:24717731

  1. The iron chelator Dp44mT inhibits the proliferation of cancer cells but fails to protect from doxorubicin-induced cardiotoxicity in spontaneously hypertensive rats

    Microsoft Academic Search

    V. Ashutosh Rao; Jun Zhang; Sarah R. Klein; Parvaneh Espandiari; Alan Knapton; Jennifer S. Dickey; Eugene Herman; Emily B. Shacter

    Purpose  The iron chelator Dp44mT is a potent topoisomerase II? inhibitor with novel anticancer activity. Doxorubicin (Dox), the current\\u000a front-line therapy for breast cancer, induces a dose-limiting cardiotoxicity, in part through an iron-mediated pathway. We\\u000a tested the hypothesis that Dp44mT can improve clinical outcomes of treatment with Dox by alleviating cardiotoxicity.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  The general cardiac and renal toxicities induced by Dox were

  2. Pulmonary hypertension produced in rats by ingestion of Crotalaria spectabilis seeds

    Microsoft Academic Search

    J. Michael Kay; Peter Harris; Donald Heath

    1967-01-01

    The oral administration of Crotalaria spectabilis seeds to young rats induces pulmonary hypertension in them associated with right ventricular hypertrophy and an increase in the medial thickness of the pulmonary trunk and muscular pulmonary arteries. This appears to be the first direct demonstration that the oral administration of an agent may bring about pulmonary hypertension.

  3. Relation of renal blood flow and cerebral blood flow at perforating artery region in essential hypertension

    Microsoft Academic Search

    K. Takatsugi; M. Mukai; H. Mawatari; K. Goya; K. Matsuzaki

    2000-01-01

    Arteriolosclerosis is an important vascular change induced by hypertension. Blood flow of kidney and perforating artery area in the brain in essential hypertensive patients are determined by the severity of arteriolosclerosis in each region. The aim of the study was to evaluate relation of effective renal plasma flow (ERPF) and regional cerebral blood flow (rCBF) including basal ganglia as perforating

  4. Possible induction of diabetes by treatment of hypertension with indapamide (with four case reports)

    Microsoft Academic Search

    Zhang Jian-liang; Qin Yong-wen; Zheng Xing; Qiu Jian-li; Cao Jiang; Xu Rong-liang

    2004-01-01

    Objective: To study therapy with indapamide impairing carbohydrate metabolism in essential hypertension patients and achieve earlier prevention, diagnoses and treatment of diabetes induced by indapamide. Methods: Four cases of essential hypertension patients (1 male and 3 females) were observed through process of therapy with indapamide and laboratory investigations. Results: After 4- to 14-month period of therapy with the combination of

  5. Chronic thromboembolic pulmonary hypertension: animal models.

    PubMed

    Mercier, Olaf; Fadel, Elie

    2013-05-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease due to pulmonary artery obstruction by persistent organised clots related to one or more episodes of acute pulmonary embolism. To date, the pathogenesis of CTEPH remains unexplained. Pulmonary endarterectomy removes obstruction from pulmonary vessels and can cure patients. However, some unreachable distal pulmonary obstruction and/or associated distal pulmonary vasculopathy could induce persistent pulmonary hypertension, the main postoperative complication. The pathophysiology of CTEPH is not fully understood and improving knowledge of this disease could improve our future surgical and medical management. Many attempts, conducted over several decades, have failed to reproduce this chronic disease in animals. However, several animal models have provided insights into the pathophysiology and pathogenesis of CTEPH. Here, we review all the animal models that have improved the comprehension of CTEPH and hold promise for further investigations. This short review analyses strengths and weaknesses of all animal models available to study the pathophysiology of CTEPH. PMID:23314897

  6. Enalapril improves heart failure induced by monocrotaline without reducing pulmonary hypertension in rats: roles of preserved myocardial creatine kinase and lactate dehydrogenase isoenzymes

    Microsoft Academic Search

    Kyosuke Ishikawa; Hidekazu Hashimoto; Sachio Mitani; Yukio Toki; Kenji Okumura; Takayuki Ito

    1995-01-01

    We investigated the redistribution of myocardial isoenzymes of creatine kinase (CK) and lactate dehydrogenase (LD) in rats with right heart failure induced by monocrotaline and assessed the effect of enalapril, an angiotensin converting enzyme inhibitor. Wistar rats were divided into four groups: (1) control (n = 20), (2) control + enalapril (25 mg\\/kg\\/day) (n = 22), (3) monocrotaline (50 mg\\/kg)

  7. Pediatric pulmonary arterial hypertension.

    PubMed

    Wu, Dan-Chen; Zhang, Hong-Da; Jing, Zhi-Cheng

    2013-12-01

    Pulmonary arterial hypertension (PAH) can cause morbidity and mortality in children. Although adult and pediatric PAH share many similarities, many differences have been found in children. Thus, a new classification for pediatric pulmonary hypertensive vascular disease has been proposed. Both child and adult gene mutation carriers with PAH tend to have worse prognoses. Pediatric patients present with better preserved functional class, and parents should pay high attention to any children with unexplained shortness of breath, fatigue or syncope, as symptoms of PAH in children are often misleading. Right heart catheterization is necessary for diagnosis. Although there are few medications approved for pediatric PAH and evidence-based treatment algorithms for children are still lacking, the survival of pediatric patients has been improved significantly since targeted therapies approved for adults were introduced to pediatric patients. PAH in children is unique, and further studies are needed to have a better understanding of it. PMID:24163011

  8. Pharmacologically induced release and modulation of /sup 3/H-norepinephrine (NE) from the isolated portal vein of the spontaneously hypertensive rat (SHR)

    SciTech Connect

    Zhang, S.Q.; Westfall, T.C.

    1986-03-05

    The purpose of the present study was to probe the mechanism for the enhancement of the field-stimulation induced release of /sup 3/H-NE from blood vessels of the SHR compared to normotensive rats. The results of two types of experiments are reported here. First, the effect of nicotine as well as tyramine in inducing the release of /sup 3/H-NE from the superfused portal vein was compared to field stimulation. Secondly, the modulatory effect of serotonin (5-HT) and methacholine (M) on the field stimulation induced release of /sup 3/H-NE was examined. In contrast to the enhancement of the field stimulation induced release of /sup 3/H-NE from the portal vein of the SHR compared to WKY, both nicotine and tyramine produced a similar release of NE from blood vessel obtained from both strains. The fractional release of /sup 3/H-NE to 10/sup -4/, 10/sup -3/ and 10/sup -2/M nicotine was 0.21, 0.67 and 45.5 from WKY and 0.14, 0.68 and 42.4 from SHR. The fractional release of /sup 3/H-NE to 10/sup -4/ and 10/sup -3/M tyramine was 6 and 17 from WKY compared to 7.5 and 17.5 from SHR. The inhibition of /sup 3/H-NE release from the portal vein by both 5-HT and M was similar in blood vessels obtained from SHR and WKY. These results are consistent with there being a defect in the exocytotic induced release of NE from noradrenergic neurons at the vascular neuroeffector junction.

  9. Hypertensive Emergencies in Children

    Microsoft Academic Search

    Pankaj Hari; Aditi Sinha

    2011-01-01

    Hypertensive emergencies, though uncommon in children, are potentially life threatening. While targeting blood pressure reduction\\u000a to below the 90th percentile for age, gender and height, mean arterial blood pressure should be gradually lowered by one-fourth\\u000a of the planned reduction over 8–12 h, a further fourth over the next 8–12 h, and the final 50% over the 24 h after that. Frequent\\u000a invasive or

  10. Chronic Thromboembolic Pulmonary Hypertension

    Microsoft Academic Search

    Lara M. Wittine; William R. Auger

    2010-01-01

    Opinion statement  The pulmonary hypertension (PH) and right heart dysfunction that results from chronic thromboembolic involvement of the pulmonary\\u000a vascular bed is potentially curable with surgical endarterectomy. Over the past several decades, growing clinical experience\\u000a has brought about increased recognition of this treatable form of PH. Moreover, advances in cardiothoracic surgical techniques\\u000a have given an increasing number of patients with chronic

  11. Lifestyle intervention in hypertension.

    PubMed

    Marley, J

    1989-05-01

    Patients are often interested in taking some responsibility for treating their own illnesses, especially in a symptom-free condition such as hypertension. Confusing information is available on non-pharmacological measures, which often results in none of these treatments being offered to the patient. This review discusses what is of value, what may be helpful and what is likely to be worthless. PMID:2602299

  12. Portal hypertensive enteropathy

    PubMed Central

    Mekaroonkamol, Parit; Cohen, Robert; Chawla, Saurabh

    2015-01-01

    Portal hypertensive enteropathy (PHE) is a condition that describes the pathologic changes and mucosal abnormalities observed in the small intestine of patients with portal hypertension. This entity is being increasingly recognized and better understood over the past decade due to increased accessibility of the small intestine made possible by the introduction of video capsule endoscopy and deep enteroscopy. Though challenged by its diverse endoscopic appearance, multiple scoring systems have been proposed to classify the endoscopic presentation and grade its severity. Endoscopic findings can be broadly categorized into vascular and non-vascular lesions with many subtypes of both categories. Clinical manifestations of PHE can range from asymptomatic incidental findings to fatal gastrointestinal hemorrhage. Classic endoscopic findings in the setting of portal hypertension may lead to a prompt diagnosis. Occasionally histopathology and cross sectional imaging like computed tomography or magnetic resonance imaging may be helpful in establishing a diagnosis. Management of overt bleeding requires multidisciplinary approach involving hepatologists, endoscopists, surgeons, and interventional radiologists. Adequate resuscitation, reduction of portal pressure, and endoscopic therapeutic intervention remain the main principles of the initial treatment. This article reviews the existing evidence on PHE with emphasis on its classification, diagnosis, clinical manifestations, endoscopic appearance, pathological findings, and clinical management. A new schematic management of ectopic variceal bleed is also proposed. PMID:25729469

  13. [Hypertension in pregnancy].

    PubMed

    Beaufils, M

    2001-10-01

    Hypertension occurs in 10 to 15 p cent of pregnancies. Among them, 10 to 20% also have proteinuria. This situation defines preeclampsia, and involves a serious threat on foetal and even maternal prognosis. Presence of the hepatic (HELLP) syndrome still severely worsens the prognosis. Pathophysiology of preeclampsia is based on a very early abnormality of placentation, leading to insufficient blood supply to the foeto-placental unit. At the maternal level, the main consequence of placental ischemia is diffuse endothelial dysfunction, responsible for systemic vasoconstriction and clotting abnormalities. In such a context, merely lowering blood pressure with drugs is quite inefficient, or even harmful. The prognosis of this disease is mainly related to the pertinence of obstetrical management. An early preventive strategy is the most logical approach of preeclampsia, its modalities remain under discussion. Hypertension has a high recurrence rate on subsequent pregnancies. It is most often linked to a high global vascular risk level, therefore many of those patients will become permanent hypertensives in the near future. PMID:11725713

  14. Ocular manifestations of systemic hypertension.

    PubMed

    Schubert, H D

    1998-12-01

    Recent population-based studies suggest that the fundus lesions of hypertension also occur in people without hypertension. In experimental studies, hypertensive lesions, which used to be the backbone of older classifications of the severity of hypertension, did not correlate sufficiently with severity to allow reliable grading. Hypertensive retinopathy, choroidopathy, and optic neuropathy are independent processes. Vascular narrowing appears to occur early in the disease process, whereas retinal hemorrhages and retinal lipid may occur later. Branch vein occlusion is a complication of hypertension, whereas open-angle glaucoma may not be. Choroidal neovascularization in the fellow eyes of patients with macular degeneration is associated with high blood pressure. Laser treatment for this disorder is less effective in patients with high blood pressure than it is in normotensive individuals, which suggests that choroidal neovascularization may be an expression of chronic hypertensive choroidopathy. Hypertensive optic neuropathy, a variant of ischemic optic neuropathy, has delayed onset compared with retinopathy and, in experimental studies, has not been linked to the severity of hypertension. Given these findings, it may be better to describe than to grade fundus lesions. In either event, it is important to take blood pressures accurately. Fundus lesions suggest high blood pressure. Sphygmomanometry is more specific and reliable than funduscopy in making that diagnosis. PMID:10387339

  15. Effects of amlodipine orotate on hypertension-related complications in spontaneously hypertensive rats.

    PubMed

    Choi, Seul Min; Kim, Jee Eun; Ahn, Byoung Ok; Kwon, Jong Won

    2006-01-01

    Hypertension is a common problem in elderly patients, which usually requires chronic therapy under various physiological conditions including low gastric acidity (hypo- or anacidity). This study investigated a new salt type of amlodipine (CAS 88150-42-9) on blood pressure and hypertension-related complications in stroke-prone spontaneously hypertensive rats (SHR-SP). Amlodipine orotate was prepared by reacting orotic acid and amlodipine to increase the dissolution rate at higher gastric pH conditions. Twelve-week-old SHR-SP were randomly divided into five groups to receive either amlodipine orotate or amlodipine besylate (CAS 111470-99-6) at the doses of 3 and 10 mg/kg/day orally for four weeks. The age-matched normotensive Wistar Kyoto rats (WKY) served as the normal positive control group. The systolic blood pressure was reduced in the amlodipine treated SHR-SP in a dose-dependent manner with a similar potency irrespective of the salt type. Both amlodipines also reduced the left ventricular hypertrophy at high doses and concentration-dependently inhibited the Ca2+ induced contraction with a similar potency. Furthermore, semi-quantitative analysis of a cerebral injury revealed that the two salts of amlodipine reduced the stroke-re-lated lesions to a similar degree. These results suggest that the amlodipine orotate is effective in terms of its effects on hypertension, cardiac hypertrophy and stroke-related cerebral damage in SHR-SP. PMID:16478000

  16. Splanchnic-aortic inflammatory axis in experimental portal hypertension

    PubMed Central

    Aller, Maria-Angeles; de las Heras, Natalia; Nava, Maria-Paz; Regadera, Javier; Arias, Jaime; Lahera, Vicente

    2013-01-01

    Splanchnic and systemic low-grade inflammation has been proposed to be a consequence of long-term prehepatic portal hypertension. This experimental model causes minimal alternations in the liver, thus making a more selective study possible for the pathological changes characteristic of prehepatic portal hypertension. Low-grade splanchnic inflammation after long-term triple partial portal vein ligation could be associated with liver steatosis and portal hypertensive intestinal vasculopathy. In fact, we have previously shown that prehepatic portal hypertension in the rat induces liver steatosis and changes in lipid and carbohydrate metabolism similar to those produced in chronic inflammatory conditions described in metabolic syndrome in humans. Dysbiosis and bacterial translocation in this experimental model suggest the existence of a portal hypertensive intestinal microbiome implicated in both the splanchnic and systemic alterations related to prehepatic portal hypertension. Among the systemic impairments, aortopathy characterized by oxidative stress, increased levels of proinflammatory cytokines and profibrogenic mediators stand out. In this experimental model of long-term triple portal vein ligated-rats, the abdominal aortic proinflammatory response could be attributed to oxidative stress. Thus, the increased aortic reduced-nicotinamide-adenine dinucleotide phosphate [NAD(P)H] oxidase activity could be associated with reactive oxygen species production and promote aortic inflammation. Also, oxidative stress mediated by NAD(P)H oxidase has been associated with risk factors for inflammation and atherosclerosis. The splanchnic and systemic pathology that is produced in the long term after triple partial portal vein ligation in the rat reinforces the validity of this experimental model to study the chronic low-grade inflammatory response induced by prehepatic portal hypertension. PMID:24307792

  17. Microglia Participate in Neurogenic Regulation of Hypertension.

    PubMed

    Shen, Xiao Z; Li, You; Li, Liang; Shah, Kandarp H; Bernstein, Kenneth E; Lyden, Patrick; Shi, Peng

    2015-08-01

    Hypertension is associated with neuroinflammation and increased sympathetic tone. Interference with neuroinflammation by an anti-inflammatory reagent or overexpression of interleukin-10 in the brain was found to attenuate hypertension. However, the cellular mechanism of neuroinflammation, as well as its impact on neurogenic regulation of blood pressure, is unclear. Here, we found that hypertension, induced by either angiotensin II or l-N(G)-nitro-l-arginine methyl ester, is accompanied by microglial activation as manifested by microgliosis and proinflammatory cytokine upregulation. Targeted depletion of microglia significantly attenuated neuroinflammation, glutamate receptor expression in the paraventricular nucleus, plasma vasopressin level, kidney norepinephrine concentration, and blood pressure. Furthermore, when microglia were preactivated and transferred into the brains of normotensive mice, there was a significantly prolonged pressor response to intracerebroventricular injection of angiotensin II, and inactivation of microglia eliminated these effects. These data demonstrate that microglia, the resident immune cells in the brain, are the major cellular factors in mediating neuroinflammation and modulating neuronal excitation, which contributes to the elevated blood pressure. PMID:26056339

  18. Mechanical properties of normotensive and hypertensive carotid and coronary arteries and their quantification 

    E-print Network

    Duraiswamy, Nandini

    2000-01-01

    model of pigs, subjected to two, five, and nine weeks of hypertension. We found that increased blood pressure induced changes in the multiaxial stress-stretch response of the tested arteries. Changes were significant both in the axial and circumferential...

  19. Hypertension (High Blood Pressure)

    NSDL National Science Digital Library

    Patient Education Institute

    This patient education program discusses hypertension including the causes, complications, risk factors, diagnosis, and management of the disease. It also explains what blood pressure is. This resource is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: This tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

  20. Management of portal hypertension

    PubMed Central

    Samonakis, D; Triantos, C; Thalheimer, U; Patch, D; Burroughs, A

    2004-01-01

    Treatment of portal hypertension is evolving based on randomised controlled trials. In acute variceal bleeding, prophylactic antibiotics are mandatory, reducing mortality as well as preventing infections. Terlipressin or somatostatin combined with endoscopic ligation or sclerotherapy is the best strategy for control of bleeding but there is no added effect of vasoactive drugs on mortality. Non-selective ß-blockers are the first choice therapy for both secondary and primary prevention; if contraindications or intolerance to ß-blockers are present then band ligation should be used. Novel therapies target the increased intrahepatic resistance caused by microcirculatory intrahepatic deficiency of nitric oxide and contraction of activated intrahepatic stellate cells. PMID:15537846

  1. Chronic thromboembolic pulmonary hypertension.

    PubMed

    Marshall, Peter S; Kerr, Kim M; Auger, William R

    2013-12-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease with high mortality and few treatment options. This article reviews the epidemiology of CTEPH and identifies risk factors for its development. The pathobiology and the progression from thromboembolic events to chronically increased right-sided pressures are discussed. The diagnosis and assessment of CTEPH requires several modalities and the role of these is detailed. The pre-operative evaluation assesses peri-operative risk and determines the likelihood of benefit from PTE. Pulmonary thromboendarterectomy (PTE) remains the treatment of choice in appropriate patients. Nonsurgical therapies for CTEPH may provide benefit in patients who cannot be offered surgery. PMID:24267304

  2. The Immune System in Hypertension

    ERIC Educational Resources Information Center

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  3. Renovascular Hypertension and Ischemic Nephropathy

    Microsoft Academic Search

    Stephen C. Textor; Lilach Lerman

    2010-01-01

    Renovascular disease remains among the most prevalent and important causes of secondary hypertension and renal dysfunction. Many lesions reduce perfusion pressure including fibromuscular diseases and renal infarction, but most are caused by atherosclerotic disease. Epidemiologic studies establish a strong association between atherosclerotic renal-artery stenosis (ARAS) and cardiovascular risk. Hypertension develops in patients with renovascular disease from a complex set of

  4. Renal Circulatory Effects of Acetazolamide in Patients With Essential Hypertension

    Microsoft Academic Search

    Yoshio Horita; Kazuaki Yakabe; Masato Tadokoro; Naofumi Suyama; Kohei Hayashida; Yuhei Kawano; Masanobu Miyazaki; Shigeru Kohno; Kouichi Taura

    2006-01-01

    Background: Reports indicate that acetazolamide (ACZ) induces the vasodilation of all vessels in animal models, as well as in small and medium kidney vessels in animal models. However, the effect of ACZ on the renal circulation of patients with essential hypertension remains unknown. In this study we examined the effects of a carbonic anhydrase inhibitor, acetazolamide (ACZ), on the renal

  5. Blood Pressure Variability and Stress Management Training for Essential Hypertension

    ERIC Educational Resources Information Center

    Garcia-Vera, Maria Paz; Sanz, Jesus; Labrador, Francisco J.

    2004-01-01

    The purpose of this study was to determine whether stress management training reduces blood pressure (BP) variability in hypertensive patients. Previous literature suggests that cardiovascular risk is not only a function of BP levels, but also of BP variability, and this partially depends on changes induced by the stress of everyday life. The…

  6. Hypertension, Anti-Hypertensive Medication Use, and Risk of Psoriasis

    PubMed Central

    Wu, Shaowei; Han, Jiali; Li, Wen-Qing; Qureshi, Abrar A.

    2014-01-01

    Importance Individuals with psoriasis are shown to have an elevated risk of hypertension, and anti-hypertensive medications, especially beta-blockers, have been linked to psoriasis development. However, the association of prior existing hypertension and anti-hypertensive medications with risk of incident psoriasis has not been accessed using prospective data. Objective To evaluate the association of hypertension and anti-hypertensive medications with risk of psoriasis based on data from the Nurses’ Health Study (NHS). Design Prospective cohort study (1996–2008). Setting Nurses’ Health Study. Participants A total of 77,728 U.S. women who provided biennially updated data on hypertension and anti-hypertensive medications. Main Outcome and Measure Physician-diagnosed psoriasis. Results We documented a total of 843 incident psoriasis cases during 1,066,339 person-years of follow-up. Compared to normotensive women, women with hypertension duration more than 6 years were at a higher risk of developing psoriasis [HR=1.27, 95% confidence interval (CI), 1.03–1.57]. In stratified analysis, the risk of psoriasis was higher among hypertensive women without medication [HR=1.49, 95% CI, 1.15–1.92] and among hypertensive women with current medication [HR=1.31, 95% CI, 1.10–1.55] when compared to normotensive participants without medication. Compared to women who never used beta-blockers, the multivariate HRs for psoriasis were 1.11 (95% CI, 0.82–1.51) for women who regularly used 1–2 years, 1.06 (95% CI, 0.79–1.40) for 3–5 years, and 1.39 (95% CI, 1.11–1.73) for 6 or more years (P for trend=0.009). There was no association between other individual anti-hypertensive drugs and risk of psoriasis. Conclusions Long-term hypertensive status is associated with an increased risk of psoriasis. Long-term regular use of beta-blockers may also increase the risk of psoriasis. PMID:24990147

  7. Inflammatory cytokines in pulmonary hypertension

    PubMed Central

    2014-01-01

    Pulmonary hypertension is an “umbrella term” used for a spectrum of entities resulting in an elevation of the pulmonary arterial pressure. Clinical symptoms include dyspnea and fatigue which in the absence of adequate therapeutic intervention may lead to progressive right heart failure and death. The pathogenesis of pulmonary hypertension is characterized by three major processes including vasoconstriction, vascular remodeling and microthrombotic events. In addition accumulating evidence point to a cytokine driven inflammatory process as a major contributor to the development of pulmonary hypertension. This review summarizes the latest clinical and experimental developments in inflammation associated with pulmonary hypertension with special focus on Interleukin-6, and its role in vascular remodeling in pulmonary hypertension. PMID:24739042

  8. Activation of Glomerular Mitogen-Activated Protein Kinases in Angiotensin TI-Mediated Hypertension

    Microsoft Academic Search

    AKINORI HAMAGUCHI; SHOKEI KIM; MASAHIKO YANO; SHINYA YAMANAKA; HIROSHI IWAO

    1998-01-01

    The in vito signal transduction pathway, responsible for hypertension-induced gbomerular injury, remains to be clar- ified. In this study, the effect of angiotensin II (Ang 11)-induced hypertension was examined on gbomerular mitogen-activated protein kinases (MAPK), including extracellular signal-regu- bated kinase (ERK) and c-jun NH,-terminal kinase (iNK), and on gbomerular transcription factors activator protein- 1 (AP- I) and Sp I. MAPK

  9. Hypertension and the kidney.

    PubMed

    Weir, M R; Wolfsthal, S D

    1991-09-01

    Pathophysiologic and hereditary mechanisms impacting on the kidneys are crucial for the initiation and maintenance of essential hypertension. An appreciation of these renal mechanisms is important for the institution of appropriate antihypertensive therapy. The clinician must develop a physiologic algorithm to control systemic blood pressure while maintaining adequate blood supply to the kidneys. This approach is particularly important in patients at higher risk for progressive renal insufficiency (i.e., older patients, blacks, diabetics, and those with chronic renal failure). Better perfusion reduces the likelihood of activating the compensatory neurohormonal systems that augment the intrarenal effects of the renin-angiotensin-aldosterone and sympathetic nervous systems, which ultimately may be responsible for renal structural changes leading to nephrosclerosis. In addition, dietary concerns are also important, particularly in the patients with evidence of early renal disease. Controlling blood pressure in a physiologic way by using drugs that can potentially dampen neurohormonal systems may prevent or at least delay the development of nephrosclerosis. Thus, the clinician should use an individualized therapeutic approach to the patient with hypertension. If nonpharmacologic means of blood pressure control are unsuccessful, an attempt should be made to blend the specific physiologic needs of the patient with specified pharmacologic antihypertensive mechanisms, paying particular attention to the preservation of renal function and perfusion. PMID:1946786

  10. Hypertensive Hypokalemic Disorders

    PubMed Central

    2007-01-01

    Hypokalemia is a common clinical problem. The kidney is responsible for long term potassium homoeostasis, as well as the serum potassium concentration. The main nephron site where K secretion is regulated is the cortical collecting duct, mainly via the effects of aldosterone. Aldosterone interacts with the mineralocorticoid receptor to increase sodium reabsorption and potassium secretion; the removal of cationic sodium makes the lumen relatively electronegative, thereby promoting passive potassium secretion from the tubular cell into the lumen through apical potassium channels. As a result, any condition that decreases the activity of renal potassium channels results in hyperkalemia (for example, amiloride intake or aldosterone deficiency) whereas their increased activity results in hypokalemia (for example, primary aldosteronism or Liddle's syndrome). The cause of hypokalemia can usually be determined from the history. If there is no apparent cause, the initial step is to see if hypokalemia is in associated with systemic hypertension or not. In the former group hypokalaemia is associated with a high mineralocorticoid effect or hyperactive sodium channel as in Liddle's syndrome. In hypertensive hypokalemic patients, measurement of the renin, aldosterone, and cortisol concentrations would be of help in differential diagnosis. PMID:24459498

  11. Hypertensive emergencies in children.

    PubMed

    Hari, Pankaj; Sinha, Aditi

    2011-05-01

    Hypertensive emergencies, though uncommon in children, are potentially life threatening. While targeting blood pressure reduction to below the 90th percentile for age, gender and height, mean arterial blood pressure should be gradually lowered by one-fourth of the planned reduction over 8-12 h, a further fourth over the next 8-12 h, and the final 50% over the 24 h after that. Frequent invasive or non-invasive blood pressure monitoring is essential, as is monitoring for sensorial alteration and loss of papillary reflexes. Few antihypertensive agents have been examined in children. Continuous intravenous infusions of short acting drugs such as nitroprusside, labetalol and nicardipine are preferred to intravenous boluses of hydralazine or diazoxide. If severe symptoms are absent, oral agents such as nifedipine, clonidine, minoxidil, hydralazine, labetalol, captopril, and prazosin may be used. Nicardipine and labetalol are particularly suited in emergencies with intracranial bleeding or ischemic stroke, while furosemide, sodium nitroprusside and nitroglycerine are useful in congestive cardiac failure. Therapy with oral antihypertensive drugs should be instituted within 6-12 h of parenteral therapy, and the latter gradually withdrawn over the next 12-48 h. Oral agents have limited application as primary therapy, except when administration of intravenous infusion is likely to be delayed. This article provides a summary of the clinical approach to evaluation and management of severe symptomatic hypertension in children. PMID:21271305

  12. Thiazolidinedione Treatment Decreases Oxidative Stress in Spontaneously Hypertensive Heart Failure Rats Through Attenuation of Inducible Nitric Oxide Synthase–Mediated Lipid Radical Formation

    PubMed Central

    Kadiiska, Maria B.; Bonini, Marcelo G.; Ruggiero, Christine; Cleland, Ellen; Wicks, Shawna; Stadler, Krisztian

    2012-01-01

    The current study was designed to test the hypothesis that inducible nitric oxide synthase (iNOS)-mediated lipid free radical overproduction exists in an insulin-resistant rat model and that reducing the accumulation of toxic metabolites is associated with improved insulin signaling and metabolic response. Lipid radical formation was detected by electron paramagnetic resonance spectroscopy with in vivo spin trapping in an obese rat model, with or without thiazolidinedione treatment. Lipid radical formation was accompanied by accumulation of toxic end products in the liver, such as 4-hydroxynonenal and nitrotyrosine, and was inhibited by the administration of the selective iNOS inhibitor 1400 W. The model showed impaired phosphorylation of the insulin signaling pathway. Ten-day rosiglitazone injection not only improved the response to an oral glucose tolerance test and corrected insulin signaling but also decreased iNOS levels. Similar to the results with specific iNOS inhibition, thiazolidinedione dramatically decreased lipid radical formation. We demonstrate a novel mechanism where a thiazolidinedione treatment can reduce oxidative stress in this model through reducing iNOS-derived lipid radical formation. Our results suggest that hepatic iNOS expression may underlie the accumulation of lipid end products and that reducing the accumulation of toxic lipid metabolites contributes to a better redox status in insulin-sensitive tissues. PMID:22315311

  13. Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries.

    PubMed

    Zou, Q; Leung, S W S; Vanhoutte, P M

    2015-08-01

    Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine contributes to these relaxations. Aortic rings of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were contracted with prostaglandin F2 ? and exposed to progressive mild hypothermia (from 37 to 31°C). Hypothermia induced endothelium-dependent, N?-nitro-l-arginine methyl ester-sensitive relaxations, which were reduced by atropine, but not by mecamylamine, in SHR but not in WKY rat aortae. The responses in SHR aortae were also reduced by acetylcholinesterase (the enzyme responsible for acetylcholine degradation), bromoacetylcholine (inhibitor of acetylcholine synthesis), hemicholinium-3 (inhibitor of choline uptake), and vesamicol (inhibitor of acetylcholine release). The mild hypothermia-induced relaxations in both SHR and WKY rat aortae were inhibited by AMTB [N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide; the transient receptor potential (TRP) M8 inhibitor]; only those in SHR aortae were inhibited by HC-067047 [2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide; TRPV4 antagonist] while those in WKY rat aortae were reduced by HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; TRPA1 antagonist]. The endothelial uptake of extracellular choline and release of cyclic guanosine monophosphate was enhanced by mild hypothermia and inhibited by HC-067047 in SHR but not in WKY rat aortae. Compared with WKY rats, the SHR preparations expressed similar levels of acetylcholinesterase and choline acetyltransferase, but a lesser amount of vesicular acetylcholine transporter, located mainly in the endothelium. Thus, mild hypothermia causes nitric oxide-dependent relaxations by opening TRPA1 channels in WKY rat aortae. By contrast, in SHR aortae, TRPV4 channels are opened, resulting in endothelial production of acetylcholine, which, in an autocrine manner, activates muscarinic receptors on neighboring cells to elicit endothelium-dependent relaxations in response to mild hypothermia. PMID:26060231

  14. Increasing trend in admissions for malignant hypertension and hypertensive encephalopathy in the United States.

    PubMed

    Polgreen, Linnea A; Suneja, Manish; Tang, Fan; Carter, Barry L; Polgreen, Philip M

    2015-05-01

    Malignant hypertension and hypertensive encephalopathy are life-threating manifestations of hypertension. These syndromes primarily occur in patients with a history of poorly controlled hypertension. The purpose of this study was to investigate national trends in hospital admissions for malignant hypertension, hypertensive encephalopathy, and essential hypertension. This was a retrospective cohort study that used the Nationwide Inpatient Sample. We identified all hospitalizations between 2000 and 2011, during which a primary diagnosis of malignant hypertension (ICD 9 code: 401.0), hypertensive encephalopathy (ICD 9 code: 437.2), or essential hypertension (ICD 9 code: 401.9) was recorded. Time series models were estimated for malignant hypertension, hypertensive encephalopathy, essential hypertension and also for the combined series. A piecewise linear regression analyses was performed to investigate whether there were changes in the trends of these series. In addition, we also compared the characteristics of patients with these diagnoses. The estimated number of admissions for both malignant hypertension and hypertensive encephalopathy increased dramatically after 2007, whereas discharges for essential hypertension fell, and there was no change in trend for the combined series. Costs rose substantially for patients with these diagnoses after 2007, but mortality significantly fell for malignant hypertension and mortality for hypertensive encephalopathy did not change. The dramatic increase in the number of hospital admissions for hypertensive encephalopathy and malignant hypertension should have resulted in dramatic increases in morbidity, but it did not. The change is most likely related to changes in coding related to diagnostic-related groups that occurred in 2007. PMID:25801877

  15. Primary aldosteronism in a referral hypertension center

    Microsoft Academic Search

    Giuseppe Regolisti; Franco Perazzoli; Aurelio Negro; Carlo Sani; Simona Davoli; Pietro Coghi; Ermanno Rossi

    2001-01-01

    Primary aldosteronism (PA) is a potentially curable form of secondary hypertension, but is regarded as being relatively rare in unselected hypertensive populations. The prevalence and characteristics of PA were evaluated on 1046 subsequent hypertensive patients (pts) sent to a referral Hypertension Center between January 1st 1997 and December 31st 1999. Screening of PA was performed with the captopril test. Final

  16. [Hypertension in the Negro patient].

    PubMed

    Timmers, G J; Schouten, J A; ter Wee, P M; Gans, R O

    1999-01-30

    Essential hypertension appears to be more prevalent among blacks than among whites and has an earlier onset in blacks. Many data in this field come from studies in the African-American population. Hypertension-related complications, e.g. ischaemic heart disease, (end stage) renal failure and cerebrovascular disease, are encountered more often among blacks and frequently run a more severe course. Factors that might explain the racial difference in prevalence of hypertension and hypertensive complications include both genetic and environmental variables. Hypertension in blacks is characterized by salt sensitivity, a tendency towards expanded plasma volume and low plasma renin levels. Socioeconomic factors, the higher prevalence of obesity and insulin resistance may contribute to the high prevalence of hypertension in blacks. Aggressive antihypertensive therapy appears mandatory in the black hypertensive, possibly with lower goal blood pressures than the 140/90 mmHg generally recommended. Diuretic monotherapy proves to be the first-line therapy, calcium channel blockers are an attractive alternative. Black patients are frequently less responsive to monotherapy with angiotensin-converting enzyme (ACE) inhibitors and beta-blocking agents. This black/white difference in therapeutic response can, however, be eliminated by addition of a diuretic. PMID:10086150

  17. The immune system in hypertension.

    PubMed

    Trott, Daniel W; Harrison, David G

    2014-03-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely contribute to end-organ damage. We and others have shown that mice lacking adaptive immune cells, including recombinase-activating gene-deficient mice and rats and mice with severe combined immunodeficiency have blunted hypertension to stimuli such as ANG II, high salt, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Agonistic antibodies to the ANG II receptor, produced by B cells, contribute to hypertension in experimental models of preeclampsia. The central nervous system seems important in immune cell activation, because lesions in the anteroventral third ventricle block hypertension and T cell activation in response to ANG II. Likewise, genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and immune cell activation. Current evidence indicates that the production of cytokines, including tumor necrosis factor-?, interleukin-17, and interleukin-6, contribute to hypertension, likely via effects on both the kidney and vasculature. In addition, the innate immune system also appears to contribute to hypertension. We propose a working hypothesis linking the sympathetic nervous system, immune cells, production of cytokines, and, ultimately, vascular and renal dysfunction, leading to the augmentation of hypertension. Studies of immune cell activation will clearly be useful in understanding this common yet complex disease. PMID:24585465

  18. The immune system in hypertension

    PubMed Central

    Trott, Daniel W.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely contribute to end-organ damage. We and others have shown that mice lacking adaptive immune cells, including recombinase-activating gene-deficient mice and rats and mice with severe combined immunodeficiency have blunted hypertension to stimuli such as ANG II, high salt, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Agonistic antibodies to the ANG II receptor, produced by B cells, contribute to hypertension in experimental models of preeclampsia. The central nervous system seems important in immune cell activation, because lesions in the anteroventral third ventricle block hypertension and T cell activation in response to ANG II. Likewise, genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and immune cell activation. Current evidence indicates that the production of cytokines, including tumor necrosis factor-?, interleukin-17, and interleukin-6, contribute to hypertension, likely via effects on both the kidney and vasculature. In addition, the innate immune system also appears to contribute to hypertension. We propose a working hypothesis linking the sympathetic nervous system, immune cells, production of cytokines, and, ultimately, vascular and renal dysfunction, leading to the augmentation of hypertension. Studies of immune cell activation will clearly be useful in understanding this common yet complex disease. PMID:24585465

  19. Perivascular adipose tissue, vascular reactivity and hypertension.

    PubMed

    Oriowo, Mabayoje A

    2015-01-01

    Most blood vessels are surrounded by a variable amount of adventitial adipose tissue, perivascular adipose tissue (PVAT), which was originally thought to provide mechanical support for the vessel. It is now known that PVAT secretes a number of bioactive substances including vascular endothelial growth factor, tumor necrosis factor-alpha (TNF-?), leptin, adiponectin, insulin-like growth factor, interleukin-6, plasminogen activator substance, resistin and angiotensinogen. Several studies have shown that PVAT significantly modulated vascular smooth muscle contractions induced by a variety of agonists and electrical stimulation by releasing adipocyte-derived relaxing (ADRF) and contracting factors. The identity of ADRF is not yet known. However, several vasodilators have been suggested including adiponectin, angiotensin 1-7, hydrogen sulfide and methyl palmitate. The anticontractile effect of PVAT is mediated through the activation of potassium channels since it is abrogated by inhibiting potassium channels. Hypertension is characterized by a reduction in the size and amount of PVAT and this is associated with the attenuated anticontractile effect of PVAT in hypertension. However, since a reduction in size and amount of PVAT and the attenuated anticontractile effect of PVAT were already evident in prehypertensive rats with no evidence of impaired release of ADRF, there is the possibility that the anticontractile effect of PVAT was not directly related to an altered function of the adipocytes per se. Hypertension is characterized by low-grade inflammation and infiltration of macrophages. One of the adipokines secreted by macrophages is TNF-?. It has been shown that exogenously administered TNF-? enhanced agonist-induced contraction of a variety of vascular smooth muscle preparations and reduced endothelium-dependent relaxation. Other procontractile factors released by the PVAT include angiotensin II and superoxide. It is therefore possible that the loss could be due to an increased amount of these proinflammatory and procontractile factors. More studies are definitely required to confirm this. PMID:24503717

  20. Haemodynamic and other studies on the renoprival hypertensive rat

    PubMed Central

    Ledingham, J. M.; Pelling, D.

    1970-01-01

    1. The optimal conditions for the development of hypertension after total nephrectomy were defined in the rat. Under these conditions, haemodynamic changes were then studied before and for 3 days after total nephrectomy in the unanaesthetized animal and compared with mock-nephrectomized controls. 2. Changes in cardiac output were followed with an electromagnetic flowmeter chronically implanted on the ascending aorta, and mean arterial pressure with an indwelling aortic cannula. 3. Haematocrit fell in animals developing hypertension, due to plasma volume expansion. Restriction of administered saline did not reduce the fall in haematocrit without also preventing development of the hypertension. 4. Cardiac output and stroke volume increased significantly on the second and third days after nephrectomy. Peripheral resistance remained unchanged and pulse rate tended to fall. 5. The increase in cardiac output appeared to be more than could be accounted for by anaemia alone, and it is suggested that plasma volume expansion was partly responsible. 6. In another group of rats developing renoprival hypertension a correlation was found between changes in plasma volume and arterial pressure over the three days. 7. Renoprival hypertension was accompanied by a slight but significant reduction in oxygen consumption in comparison with the controls. 8. No relationship was found between the changes in blood pressure, and plasma sodium and potassium levels. 9. It is concluded that the observed rise in cardiac output associated with renoprival hypertension as induced in this study was not attributable to anaemia nor to a rise in metabolic rate. The implications of this situation are discussed in relation to a theory of the pathogenesis of hypertension and the findings of other workers. ImagesFig. 9 PMID:5500786

  1. Lercanidipine in Hypertension

    PubMed Central

    Borghi, Claudio

    2005-01-01

    Lercanidipine is a lipophilic, dihydropyridine calcium antagonist with a long receptor half-life. Its slow onset of action helps to avoid reflex tachycardia associated with other dihydropyridines (DHPs). It produces even and sustained blood pressure lowering with once-daily dosing. It has equivalent antihypertensive efficacy to many other agents and is effective as initial monotherapy or in combination. Efficacy has been demonstrated in elderly as well as younger patients and also in the presence of other risk factors. Lercanidipine is well tolerated with DHP-associated adverse effects occurring early in treatment. The incidence of pedal edema and subsequent withdrawals has been found to be lower with lercanidipine than with amlodipine or nifedipine gastrointestinal transport system. Preclinical and preliminary clinical findings suggest lercanidipine may have beneficial effects on atherosclerosis and left ventricular hypertrophy. The efficacy and tolerability profiles of lercanidipine make it a suitable choice for treating hypertension in a wide range of affected patients. PMID:17319103

  2. Chronic thromboembolic pulmonary hypertension.

    PubMed

    Hoeper, Marius M; Madani, Michael M; Nakanishi, Norifumi; Meyer, Bernhard; Cebotari, Serghei; Rubin, Lewis J

    2014-07-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but debilitating and life-threatening complication of acute pulmonary embolism. CTEPH results from persistent obstruction of pulmonary arteries and progressive vascular remodelling. Not all patients presenting with CTEPH have a history of clinically overt pulmonary embolism. The diagnostic work-up to detect or rule out CTEPH should include ventilation-perfusion scintigraphy, which has high sensitivity and a negative predictive value of nearly 100%. CT angiography usually reveals typical features of CTEPH, including mosaic perfusion, part or complete occlusion of pulmonary arteries, and intraluminal bands and webs. Patients with suspected CTEPH should be referred to a specialist centre for right-heart catheterisation and pulmonary angiography. Surgical pulmonary endarterectomy remains the treatment of choice for CTEPH and is associated with excellent long-term results and a high probability of cure. For patients with inoperable CTEPH, various medical and interventional therapies are being developed. PMID:24898750

  3. [Hypertension in pregnancy].

    PubMed

    Lunati, Fabio; Dugnani, Maurizio; Campanini, Mauro

    2008-09-01

    In literature, there is not an unanimous agreement on the definition of hypertension in pregnancy. The most severe complications are pre-eclampsia and eclampsia which need an early diagnosis to be avoided. The problem of therapy is discussed: there is no evidence about the positive effect of a pharmacological treatment on the maternal and/or fetal clinical outcomes. In case of blood pressure < 180/110 mmHg, the alpha metil dopa is the first choice drug. Among calcium-antagonist drugs, the efficacy of nifedipine is proved; and in the pre-eclampsia, metil dopa, beta blockers and idralazine. Many questions are anyway still unsolved needing more studies. PMID:19044251

  4. Psychological symptoms and intermittent hypertension following acute microwave exposure.

    PubMed

    Forman, S A; Holmes, C K; McManamon, T V; Wedding, W R

    1982-11-01

    Two men who were accidentally, acutely irradiated with X-band microwave radiation have been followed up clinically for 12 months. Both men developed similar psychological symptoms, which included emotional lability, irritability, headaches, and insomnia. Several months after the incidents, hypertension was diagnosed in both patients. No organic basis for the psychological problems could be found nor could any secondary cause for the hypertension. A similar syndrome following microwave exposure has been described by the East Europeans. The two cases we report, with comparable subjective symptoms and hypertension following a common exposure, provide further strong, circumstantial evidence of cause and effect. A greater knowledge of the mechanisms involved in bioeffects which may be induced by radiofrequency and microwave radiation is definitely needed. PMID:7175588

  5. Arsenic and diabetes and hypertension in human populations: A review

    SciTech Connect

    Chen, C.-J. [Genomics Research Center, Academia Sinica, 128 Academia Road Section 2, Nankang, Taipei 11529, Taiwan (China); Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Miaoli, Taiwan Institute of Statistical Science, Academia Sinica, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University, Taipei, Taiwan (China); School of Public Health, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, Tzu-Chi University, Hualien, Taiwan (China); Graduate Institute of Preventive Medicine, National Taiwan University, Taipei, Taiwan (China)], E-mail: cjchen@ha.mc.ntu.edu.tw; Wang, S.-L.; Chiou, J.-M.; Tseng, C.-H.; Chiou, H.-Y.; Hsueh, Y.-M.; Chen, S.-Y.; Wu, M.-M.; Lai, M.-S. [Genomics Research Center, Academia Sinica, 128 Academia Road Section 2, Nankang, Taipei 11529, Taiwan (China); Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Miaoli, Taiwan Institute of Statistical Science, Academia Sinica, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University, Taipei, Taiwan (China); School of Public Health, Taipei Medical University, Taipei, Taiwan (China); Department of Public Health, Tzu-Chi University, Hualien, Taiwan (China); Graduate Institute of Preventive Medicine, National Taiwan University, Taipei, Taiwan (China)

    2007-08-01

    Long-term exposure to ingested arsenic from drinking water has been well documented to be associated with an increased risk of diabetes mellitus and hypertension in a dose-response relationship among residents of arseniasis-endemic areas in southwestern Taiwan and Bangladesh. An increased risk of self-reported hypertension but not diabetes was reported in a community-based study of residents who consumed drinking water with a low level of arsenic. Increased glycosylated hemoglobin level and systolic blood pressure were observed in workers occupationally exposed to arsenic. Inconsistent findings of arsenic and diabetes in occupational studies may result from the healthy worker effect and the variation in exposure measurement, age composition, number of patients, accuracy in diagnosis and classification of underlying causes of death, competing causes of death, and method to detect diabetes. The dose-response relationship and toxicological mechanisms of arsenic-induced diabetes and hypertension need further elucidation.

  6. Clinical overview of hypertensive crisis in children

    PubMed Central

    Yang, Wen-Chieh; Lin, Mao-Jen; Chen, Chun-Yu; Wu, Han-Ping

    2015-01-01

    Hypertensive emergencies and hypertensive urgencies in children are uncommonly encountered in the pediatric emergency department and intensive care units, but the diseases are potentially a life-threatening medical emergency. In comparison with adults, hypertension in children is mostly asymptomatic and most have no history of hypertension. Additionally, measuring accurate blood pressure values in younger children is not easy. This article reviews current concepts in pediatric patients with severe hypertension.

  7. Chronic administration of aqueous extract of Hibiscus sabdariffa attenuates hypertension and reverses cardiac hypertrophy in 2K-1C hypertensive rats

    Microsoft Academic Search

    I. P. Odigie; R. R. Ettarh; S. A. Adigun

    2003-01-01

    The effect of aqueous extract of petals of Hibiscus sabdariffa (HS) on the established stages of 2-Kidney, 1-Clip renovascular hypertension was investigated in Sprague–Dawley rats. Renovascular hypertension was induced by subjecting the animals to left renal artery clamping using a 0.2mm silver clip under ether anesthesia. Sham-operated (Sh-Op) rats served as controls.Six weeks after renal artery clamping, one group of

  8. Hypertension and insulin resistance: implications of mitochondrial dysfunction.

    PubMed

    Manucha, Walter; Ritchie, Bob; Ferder, León

    2015-01-01

    Mitochondria are the primary generators of cellular reactive oxygen species (ROS); their pathophysiological roles in hypertension and insulin resistance are but imperfectly understood. Mitochondrial dysfunction has been linked to the etiologies of many complex diseases, but many other factors, including the upregulation of the renin-angiotensin system (RAS) and vitamin D deficiency, have also been implicated in hypertension pathogenesis. Hypertension resulting from the disruption of the RAS contributes to the risk of cardiovascular disease. Likewise, experimental and clinical evidence indicate that RAS stimulation and low vitamin D levels are inversely related and represent risk factors associated with the pathogenesis of hypertension. Furthermore, RAS activation induces insulin resistance, resulting in increases in ROS levels. High levels of ROS are harmful to cells, having the potential to trigger both mitochondrial-mediated apoptosis and the degradation of the mitochondrial DNA. Diabetes risk is also associated with high levels of oxidative stress; taking vitamin D, however, may reduce that risk. The finding that mitochondria possess both a functional RAS and vitamin D receptors is the starting point for improving our understanding of the interaction of mitochondria and chronic disease states, which understanding should lead to decreases in the chronic disease burden attributable to hypertension, diabetes, or both. PMID:25432896

  9. Smooth Muscle-Mediated Connective Tissue Remodeling in Pulmonary Hypertension

    NASA Astrophysics Data System (ADS)

    Mecham, Robert P.; Whitehouse, Loren A.; Wrenn, David S.; Parks, William C.; Griffin, Gail L.; Senior, Robert M.; Crouch, Edmond C.; Stenmark, Kurt R.; Voelkel, Norbert F.

    1987-07-01

    Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to fourfold increase in elastin production was observed in pulmonary artery tissue and medial smooth muscle cells from hypertensive calves. This stimulation of elastin production was accompanied by a corresponding increase in elastin messenger RNA consistent with regulation at the transcriptional level. Conditioned serum harvested from cultures of pulmonary artery smooth muscle cells isolated from hypertensive animals contained one or more low molecular weight elastogenic factors that stimulated the production of elastin in both fibroblasts and smooth muscle cells and altered the chemotactic responsiveness of fibroblasts to elastin peptides. These results suggest that connective tissue changes in the pulmonary vasculature in response to pulmonary hypertension are orchestrated by the medial smooth muscle cell through the generation of specific differentiation factors that alter both the secretory phenotype and responsive properties of surrounding cells.

  10. ?3-adrenoceptors inhibit stimulated norepinephrine release in spontaneously hypertensive rats

    PubMed Central

    Berg, Torill

    2014-01-01

    Here, the influence of ?3-adrenoceptors on catecholamine release in normotensive and spontaneously hypertensive rats was analyzed. Blood pressure was recorded through a femoral artery catheter, and cardiac output by ascending aorta flow. Time from onset of flow to maximum rise in flow indicated inotropy. Total peripheral vascular resistance (TPR) was calculated. Norepinephrine release was stimulated with tyramine, which allowed presynaptic release-control to be reflected as changes in the plasma norepinephrine concentration. ?3-adrenoceptor agonist (BRL37344) reduced baseline vascular resistance, the tyramine-stimulated norepinephrine overflow and the positive inotropic response to tyramine in hypertensive but not normotensive rats. ?3-adrenoceptor antagonist (SR59230A) reduced tyramine-stimulated norepinephrine release in both strains and the secretion of epinephrine in hypertensive rats. SR59230A reduced tyramine-induced tachycardia in normotensive rats, and prevented down-regulation of the tyramine-induced rise in resistance in hypertensive rats. It was concluded that the contradicting results obtained by agonist vs. antagonist, could be explained by their interaction with two different ?-adrenoceptors: The BRL37344-dependent inhibition of stimulated norepinephrine release and positive inotropic response to tyramine was compatible with stimulation of ?3-adrenoceptor coupling to inhibitory G-protein. This was observed only in hypertensive rats during stimulated, high levels of circulating catecholamines. The effect of BRL37344 on baseline vascular resistance was compatible with activation of ?3-adrenoceptor coupling to endothelial nitric oxide synthase. The inhibitory effect of SR59230A on tyramine-stimulated norepinephrine release in both strains, the increased TPR-response to tyramine in hypertensive rats and tachycardia in normotensive rats may result from inhibition of the low-affinity-state ?1-adrenoceptor, also known as the putative ?4-adrenoceptor. PMID:25566095

  11. Hypertension and nephrosclerosis: a reappraisal and a new theory of renal ischemia.

    PubMed

    Moore, S

    1967-02-25

    An observation in human autopsy material showing a statistically close relationship between complicated atherosclerosis of the aorta, at or above the renal artery take-off, and nephrosclerosis of usual type (i.e. the "granular kidney" of essential hypertension) led to a study of platelet aggregates as a cause of renal lesions. The renal cortical surface is peculiarly sensitive to ischemic damage. When an embolic source, which sheds repeatedly, was placed in the thoracic aorta of rabbits, they became hypertensive. The hypertension persisted for six months, at which time the kidneys showed nephrosclerosis characterized by surface cortical lesions consisting of shrunken glomeruli and atrophical tubules, subtended by arterioles whose intimas showed fibrous thickening. It is suggested that the renal component of the hypertension so induced is transitory, serving as a trigger mechanism for sustained hypertension. PMID:6020068

  12. [Surgically curable hypertension (author's transl)].

    PubMed

    Gilloz, A; Tostain, J; Richard, A; Peyrard, A; Drogue, M

    A case of hypertension was cured by simultaneous surgical treatment of an obstructive urolithiasis associated with a pheochromocytoma. Primary devascularization of the adrenal tumor, reducing blood pressure and cardiac rhythm variations was allowed by preoperative arteriography. PMID:6275533

  13. Intracranial Hypertension: Medication and Surgery

    MedlinePLUS

    ... with idiopathic intracranial hypertension (IIH) were treated with octreotide, a synthetic hormone that is sometimes used in ... endocrine disorders. The results were very positive but octreotide as a possible therapy for IIH needs to ...

  14. Schistosomiasis-associated pulmonary hypertension

    PubMed Central

    Mocumbi, Ana Olga H.; Kim, Nick H.; Mandel, Jess

    2014-01-01

    Abstract Schistosomiasis, a parasite-borne disease, is highly prevalent in Africa and Asia; it is estimated that close to 20 million people worldwide have a severe form of the disease. The chronic form can affect the gastrointestinal system and lead to hepatosplenic disease, and it may cause cardiopulmonary complications, including pulmonary hypertension. The exact pathogenesis of schistosomiasis-associated pulmonary hypertension (Sch-PH) remains unclear, although several mechanisms, including parasitic arterial embolization, pulmonary arteriopathy, and portopulmonary hypertension–like pathophysiology, have been suggested. The immunopathology of the disease is also unclear, although there are similarities with the immunology of idiopathic pulmonary arterial hypertension (PAH). Finally, the treatment of Sch-PH has not been well studied. There is some evidence on treating the underlying infection, with unclear effect on Sch-PH, and advanced PAH therapies are now being suggested, but more studies are needed to confirm their efficacy. PMID:25610596

  15. Sildenafil treatment for portopulmonary hypertension

    Microsoft Academic Search

    F. Reichenberger; R. Voswinckel; E. Steveling; B. Enke; A. Kreckel; H. Olschewski; F. Grimminger; W. Seeger; H. A. Ghofrani

    2006-01-01

    Portopulmonary hypertension (POPH) is regarded as a subtype of pulmonary arterial hypertension (PAH); however, established PAH therapies have not been evaluated for this condition. The current authors treated 14 patients (four male, 10 female; mean (range) age 55 (39-75) yrs) with moderate (n51) or severe (n513) POPH caused by alcoholic liver disease (n57), chronic viral hepatitis (n53), autoimmune hepatitis (n53),

  16. Chronic Psychosocial Stress and Hypertension

    Microsoft Academic Search

    Tanya M. Spruill

    2010-01-01

    Genetic and behavioral factors do not fully explain the development of hypertension, and there is increasing evidence suggesting\\u000a that psychosocial factors may also play an important role. Exposure to chronic stress has been hypothesized as a risk factor\\u000a for hypertension, and occupational stress, stressful aspects of the social environment, and low socioeconomic status have\\u000a each been studied extensively. The study

  17. Spousal Caregiving and Incident Hypertension

    Microsoft Academic Search

    Benjamin D. Capistrant; J. Robin Moon; M. Maria Glymour

    2012-01-01

    BackgroundCaring for one's spouse has been associated with poor health, including risk of cardiovascular disease (CVD) onset and mortality. However, few studies have assessed the risk of incident hypertension associated with spousal caregiving. This paper investigates this association in a large, nationally representative sample of American older adults.MethodsMarried, hypertension-free, Health and Retirement Study (HRS) respondents aged 50+ in 2000, (n

  18. The immune system in hypertension.

    PubMed

    Harrison, David G

    2014-01-01

    Hypertension is generally attributed to perturbations of the vasculature, the kidney, and the central nervous system. During the past several years, it has become apparent that cells of the innate and adaptive immune system also contribute to this disease. Macrophages and T cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension, and likely contribute to end-organ damage. We have shown that mice lacking lymphocytes, such as recombinase-activating gene-deficient (RAG-1(-/-)) mice, have blunted hypertension in response to angiotensin II, increased salt levels, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Others have shown that mice with severe combined immunodeficiency have blunted hypertension in response to angiotensin II. Deletion of the RAG gene in Dahl salt-sensitive rats reduces the hypertensive response to salt feeding. The central nervous system seems to orchestrate immune cell activation. We produced lesions of the anteroventral third ventricle and showed that these block T cell activation in response to angiotensin II. Likewise, we showed that genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and T cell activation. Current evidence indicates that production of cytokines including tumor necrosis factor alpha, interleukin 17, and interleukin 6 contribute to hypertension, likely by promoting vasoconstriction, production of reactive oxygen species, and sodium reabsorption in the kidney. We propose a working hypothesis linking the sympathetic nervous system, immune cells, the production of cytokines, and ultimately vascular and renal dysfunction, leading to augmentation of hypertension. PMID:25125726

  19. Genetic Effects of Blood Pressure Quantitative Trait Loci on Hypertension-Related Organ Damage: Evaluation Using Multiple Congenic Strains

    Microsoft Academic Search

    Noriyoshi Ishikawa; Yuji Harada; Riruke Maruyama; Junichi Masuda; Toru Nabika

    2008-01-01

    On rat chromosome 1, quantitative trait loci (QTLs) for susceptibility to hypertension-related renal diseases and cerebral stroke are identified in a cluster, some of which have been previously claimed to be independent of hypertension. In this study, we therefore attempted to excise genomic regions contributing to salt-induced renal damage and cerebral stroke using five congenic rats for blood pressure QTL

  20. A neuroendocrine model of obesity worsen insulin resistance of spontaneously hypertensive rats: a new model of type 2 diabetes

    Microsoft Academic Search

    Carolina B. N. Ferreira; Andrea P. Pastore; Mario L. R. Cesaretti; Milton Ginoza; Maria Tereza Zanella; Artur B. Ribeiro; Osvaldo Kohlmann

    2003-01-01

    Obesity is frequently associated with hypertension and type 2 diabetes caracterized by an insulin resistance state, but in general models of inducible obesity in rats do not show an elevated blood pressure (BP).Aim: to evaluate the effects of an neuroendocrine model of obesity, eg neonatal monosodium glutamate (MSG) administration, on BP and glucose metabolism of spontaneously hypertensive rats (SHR).Methods: SHR

  1. Aliskiren versus ramipril in hypertension.

    PubMed

    Verdecchia, Paolo; Angeli, Fabio; Mazzotta, Giovanni; Martire, Paola; Garofoli, Marta; Gentile, Giorgio; Reboldi, Gianpaolo

    2010-06-01

    Aliskiren is an orally active direct renin inhibitor which inhibits the synthesis of angiotensin I by linking to active renin on a deep cleft of its molecular structure, the site of hydrolysis of the Leu10-Val11 bond of angiotensinogen. At variance with angiotensin-converting enzyme (ACE) inhibitors, aliskiren eliminates the main substrate for the 'escape' phenomenon (synthesis of angiotensin II from angiotensin I through alternative enzymatic pathways). The possibility that the antihypertensive effect of aliskiren differs from that of ACE inhibitors needs to be proved in specifically designed clinical trials. Over the past 2 years, three studies have been published which directly compared aliskiren with ramipril, in patients with hypertension. We made a pooled analysis of these studies. In order to avoid interference with additional drugs, analysis was restricted to trial periods when the two drugs were given as monotherapy. In each individual study, systolic blood pressure (BP) was slightly lower with aliskiren. Overall, systolic BP was lower with aliskiren than with ramipril (weighted mean difference between the treatments 1.84 mmHg; fixed effect model; p < 0.0001; and 1.87 mmHg; random effect model; p = 0.0055). The standardized mean difference between the treatments was 2.58 (fixed effect model; p < 0.0001) and 2.92 (random effect model; p = 0.0017) in favor of aliskiren. Compared with ramipril, aliskiren may have induced a more complete 'upstream' inhibition of the renin-angiotensin-aldosterone system, with consequent greater suppression of angiotensin II. Another potential explanation may be the longer terminal elimination halflife of aliskiren (about 40 hours) compared with ramiprilat (13-17 hours). These data provide further evidence that aliskiren monotherapy provides a sustained BP reduction over the 24 hours. PMID:20418269

  2. Prevalence of Hypertension in HIV-Positive Patients on Highly Active Retroviral Therapy (HAART) Compared with HAART-Naďve and HIV-Negative Controls: Results from a Norwegian Study of 721 Patients

    Microsoft Academic Search

    B. M. Bergersen; L. Sandvik; O. Dunlop; K. Birkeland; J. N. Bruun

    2003-01-01

    Highly active antiretroviral therapy (HAART) may induce dyslipidemia, insulin resistance and body fat distribution similar to that seen in the metabolic syndrome. Hypertension is often a part of the classic metabolic syndrome, but few studies are published about hypertension in HIV-positive patients on HAART. The aim of this study was to compare the prevalence of hypertension in HIV-positive patients on

  3. Central cardiovascular circuits contribute to the neurovascular dysfunction in angiotensin II hypertension.

    PubMed

    Capone, Carmen; Faraco, Giuseppe; Peterson, Jeffrey R; Coleman, Christal; Anrather, Josef; Milner, Teresa A; Pickel, Virginia M; Davisson, Robin L; Iadecola, Costantino

    2012-04-01

    Hypertension, a powerful risk factor for stroke and dementia, has damaging effects on the brain and its vessels. In particular, hypertension alters vital cerebrovascular control mechanisms linking neural activity to cerebral perfusion. In experimental models of slow-developing hypertension, free radical signaling in the subfornical organ (SFO), one of the forebrain circumventricular organs, is critical for the hormonal release and sympathetic activation driving the elevation in arterial pressure. However, the contribution of this central mechanism to the cerebrovascular alterations induced by hypertension remains uncertain. We tested the hypothesis that free radical production in the SFO is involved in the alterations in cerebrovascular regulation produced by hypertension. In a mouse model of gradual hypertension induced by chronic administration of subpressor doses of angiotensin II (AngII), suppression of free radicals in the SFO by overexpression of CuZn-superoxide dismutase (CuZnSOD) prevented the alteration in neurovascular coupling and endothelium-dependent responses in somatosensory cortex induced by hypertension. The SFO mediates the dysfunction via two signaling pathways. One involves SFO-dependent activation of the paraventricular hypothalamic nucleus, elevations in plasma vasopressin, upregulation of endothelin-1 in cerebral resistance arterioles and activation of endothelin type A receptors. The other pathway depends on activation of cerebrovascular AngII type 1 (AT1) receptors by AngII. Both pathways mediate vasomotor dysfunction by inducing vascular oxidative stress. The findings implicate for the first time the SFO and its efferent hypothalamic pathways in the cerebrovascular alterations induced by AngII, and identify vasopressin and endothelin-1 as potential therapeutic targets to counteract the devastating effects of hypertension on the brain. PMID:22492044

  4. Surgical Treatment of Cervical Spondylotic Myelopathy Associated Hypertension—A Retrospective Study of 309 Patients

    PubMed Central

    Jia, Wen-yu; Wang, Xia; Chen, Bin; Shahbaz, Muhammad; Nie, Lin; Cheng, Lei

    2015-01-01

    Hypertension is the most prevalent cardiovascular disease, and various risk factors are known to be involved in it. Cervical spondylotic myelopathy (CSM) is the most common non-traumatic cause of myelopathy, which displays neurological symptoms and may induce systemic symptoms. To date, it is still unknown whether CSM is associated with hypertension, and if so, whether the decompression operations can attenuate CSM associated hypertension. Here, a total of 309 patients with CSM who received anterior or posterior decompression surgery were enrolled as subjects. Blood pressure measurements were performed before and within one week after the surgery. Among the 309 subjects, 144 (46.6%) of them exhibited hypertension before surgery, a significantly higher ratio than that of the whole population. One week after surgery, blood pressure of 106 (73.6%) patients turned back to normal. Blood pressure of another 37(25.7%) patients decreased with different degrees, although still higher than normal. Moreover, it appears that both approaches were effective in improving blood pressure, while the posterior approach was more effective in decreasing systolic blood pressure. We speculate this type of hypertension might result from hyperactivity of sympathetic nervous system as the heart rate of these patients decreased after surgery as well. Collectively, compression of spinal cord in CSM patients might be associated with hypertension, and decompression surgery largely attenuated this type of hypertension. These findings prove CSM to be a potential associated factor of high blood pressure and may shed light on therapies of hypertension in clinics. PMID:26193469

  5. Electrophysiological Studies in Patients with Pulmonary Hypertension: A Retrospective Investigation

    PubMed Central

    Bandorski, Dirk; Schmitt, Jörn; Kurzlechner, Claudia; Erkapic, Damir; Hamm, Christian W.; Seeger, Werner; Ghofrani, Ardeschir; Höltgen, Reinhard; Gall, Henning

    2014-01-01

    Few studies have investigated patients with pulmonary hypertension and arrhythmias. Data on electrophysiological studies in these patients are rare. In a retrospective dual-centre design, we analysed data from patients with indications for electrophysiological study. Fifty-five patients with pulmonary hypertension were included (Dana Point Classification: group 1: 14, group 2: 23, group 3: 4, group 4: 8, group 5: 2, and 4 patients with exercised-induced pulmonary hypertension). Clinical data, 6-minute walk distance, laboratory values, and echocardiography were collected/performed. Nonsustained ventricular tachycardia was the most frequent indication (n = 15) for an electrophysiological study, followed by atrial flutter (n = 14). In summary 36 ablations were performed and 25 of them were successful (atrial flutter 12 of 14 and atrioventricular nodal reentrant tachycardia 4 of 4). Fluoroscopy time was 16 ± 14.4 minutes. Electrophysiological studies in patients with pulmonary hypertension are feasible and safe. Ablation procedures are as effective in these patients as in non-PAH patients with atrial flutter and atrioventricular nodal reentrant tachycardia and should be performed likewise. The prognostic relevance of ventricular stimulations and inducible ventricular tachycardias in these patients is still unclear and requires further investigation. PMID:24977152

  6. Angiotensin II-related hypertension and eye diseases

    PubMed Central

    Marin Garcia, Pablo Jesus; Marin-Castańo, Maria Encarna

    2014-01-01

    Systemic vascular disease, especially hypertension, has been suspected as a risk factor for some eye diseases including, diabetic retinopathy and age-related macular degeneration. Hypertension can contribute to chronic diseases by hemodynamic injury and/or cellular actions induced by hypertension-related hormones or growth factors. Among the most important is Angiotensin II (Ang II), which controls blood pressure and induces different cellular functions that may be dependent or independent of its effect on blood pressure. Importantly, as is true for heart, kidney and other organs, the renin-angiotensin system (RAS) is present in the eye. So, even in the absence of hypertension, local production of Ang II could be involved in eye diseases. The goal of this manuscript is to review the most relevant scientific evidence supporting the role of the RAS activation, in the development of age-related macular degeneration and diabetic retinopathy, and highlight the importance of Ang II in the etiology of these diseases. PMID:25276298

  7. Sildenafil Inhibits Hypoxia-Induced Pulmonary Hypertension

    Microsoft Academic Search

    L. Zhao; N. A. Mason; N. W. Morrell; B. Kojonazarov; A. Sadykov; A. Maripov; M. M. Mirrakhimov; A. Aldashev; M. R. Wilkins

    2001-01-01

    Background—This study investigated the effect of the phosphodiesterase 5 inhibitor sildenafil on the pulmonary vascular response to hypoxia in humans and mice. Methods and Results—In a randomized, double-blind study, sildenafil 100 mg or placebo was given orally to 10 healthy volunteers 1 hour before breathing 11% O2 for 30 minutes. Pulmonary artery pressure (PAP) was measured with an indwelling right

  8. [Postpartum pulmonary hypertension].

    PubMed

    Escalante, Juan Pablo; Diez, Ana; Figueroa Casas, Marcelo; Lasave, Alejandro; Cursack, Guillermo; Poy, Carlos; Rodríguez, María Soledad; Galuppo, Marcela; Zapata, Gerardo

    2015-01-01

    Pulmonary hypertension (PH) in pregnancy is a rare disorder that carries a high risk to mother and child, and as such, it is considered a contraindication to becoming pregnant. However, there are few published reports related to the diagnosis of this condition after delivery. We describe three PH cases diagnosed after their normal pregnancies and deliveries. Although the causes are unknown, several mechanisms such as hypercoagulation, placental hypoxia or amniotic fluid embolism have been considered as possible causes. It is difficult to define whether a PH diagnosed in the postpartum period, relates to an earlier asymptomatic PH period that was triggered by the physiological stress of labor or if it is a recently acquired condition. Despite the lack of data to support the absence of PH previous to pregnancy in our three patients, lack of events during this period, asymptomatic and normal deliveries, lead us to believe that they did not suffer this disease prior to pregnancy; considering that high hemodynamic demands impair a ventricle with little reserve, and its subsequent appearance at time of delivery. PMID:25637900

  9. Primary aldosteronism and hypertensive disease.

    PubMed

    Mosso, Lorena; Carvajal, Cristian; González, Alexis; Barraza, Adolfo; Avila, Fernando; Montero, Joaquín; Huete, Alvaro; Gederlini, Alessandra; Fardella, Carlos E

    2003-08-01

    Recent studies in hypertensive populations that have used the serum aldosterone (SA) to plasma renin activity (PRA) ratio as a screening test have demonstrated a high prevalence of primary aldosteronism (PA). This frequency is higher than that previously described when hypokalemia was used as a screening tool. However, other factors, such as the characteristics of hypertensive disease, could also influence the prevalence of PA. We studied 609 essential hypertensive patients, classified according to the Joint National Committee VI (JNC VI), in 3 different stages depending on the severity of their hypertensive disease. We measured SA and PRA and calculated the SA-PRA ratio for all patients. An SA-PRA ratio >25 was detected in 63 of 609 patients, and the fludrocortisone test confirmed the PA diagnoses in 37 of 609 (6.1%) cases. PA prevalence according to hypertension stage was as follows: stage 1, 6 of 301 cases (1.99%); stage 2, 15 of 187 cases (8.02%); and stage 3, 16 of 121 cases (13.2%). PA patients were slightly younger than the other hypertensive patients (48.4+/-10.5 vs 53.6+/-10.2 years; P<0.05). Serum potassium levels were normal in 36 of 37 PA patients; only 1 patient had minor hypokalemia. Computed tomography scans showed bilateral adrenal enlargement in 7 and an adrenal nodule in 2 cases. In summary, we found a high frequency of PA in essential hypertensives classified in stages 2 and 3 according to the JNC VI. The low frequency of computed tomography scan abnormalities and hypokalemia suggests that the diagnosis for most PA patients corresponds to attenuated forms of the disease. PMID:12796282

  10. Regional cerebral blood flow and arterial blood volume and their reactivity to hypercapnia in hypertensive and normotensive rats.

    PubMed

    Kim, Tae; Richard Jennings, J; Kim, Seong-Gi

    2014-03-01

    Chronic hypertension induces cerebrovascular remodeling, changing the inner diameter and elasticity of arterial vessels. To examine cerebrovascular morphologic changes and vasodilatory impairment in early-stage hypertension, we measured baseline (normocapnic) cerebral arterial blood volume (CBV(a)) and cerebral blood flow (CBF) as well as hypercapnia-induced dynamic vascular responses in animal models. All experiments were performed with young (3 to 4 month old) spontaneously hypertensive rats (SHR) and control Wistar-Kyoto rats (WKY) under ?1% isoflurane anesthesia at 9.4 Tesla. Baseline regional CBF values were similar in both animal groups, whereas SHR had significantly lower CBV(a) values, especially in the hippocampus area. As CBF is maintained by adjusting arterial diameters within the autoregulatory blood pressure range, CBV(a) is likely more sensitive than CBF for detecting hypertensive-mediated alterations. Unexpectedly, hypercapnia-induced CBF and blood-oxygenation-level-dependent (BOLD) response were significantly higher in SHR as compared with WKY, and the CBF reactivity was highly correlated with the BOLD reactivity in both groups. The higher reactivity in early-stage hypertensive animals indicates no significant vascular remodeling occurred. At later stages of hypertension, the reduced vascular reactivity is expected. Thus, CBF and CBV(a) mapping may provide novel insights into regional cerebrovascular impairment in hypertension and its progression as hypertension advances. PMID:24252849

  11. [Pulmonary hypertension in liver diseases].

    PubMed

    Savale, Laurent; Sattler, Caroline; Sitbon, Olivier

    2014-09-01

    Portopulmonary hypertension (PoPH) is defined by the combination of portal hypertension and precapillary pulmonary hypertension (mPAP ? 25 mmHg, PCWP < 15 mmHg and PVR > 3 Wood units). PoPH is characterised by pathobiological mechanisms that are similar to other forms of pulmonary arterial hypertension. Prevalence of PoPH is estimated at 0.5-5% among patients with portal hypertension with or without cirrhosis. Treatment strategies most commonly employed for PoPH patients are based on recommendations for idiopathic PAH management. Indeed, the choice of specific PAH treatment must take account the severity of the underlying liver disease. Prognosis of PoPH patients is dependent on both the severity of PAH and of the underlying liver disease. PoPH may be a contraindication for orthotopic liver transplantation (OLT) if mean pulmonary arterial pressure is > 35 mmHg associated with severe right ventricular dysfunction or high level of pulmonary vascular resistance (> 3-4 Wood units). Bridge therapy with specific PAH therapies should be considered in those patients in an attempt to improve pulmonary hemodynamic and thereby allow OLT with acceptable risk. Recent data suggest that stabilize, improve or cure PoPH seems to be possible by combining specific PAH therapies and liver transplantation in selected patients. Clinical and experimental evidences suggest that IFN therapy may be a possible risk factor for PAH. PMID:25148949

  12. Liver cirrhosis and arterial hypertension

    PubMed Central

    Henriksen, Jens H; Moller, Soren

    2006-01-01

    Characteristic findings in patients with cirrhosis are vasodilatation with low overall systemic vascular resistance, high arterial compliance, increased cardiac output, secondary activation of counter-regulatory systems (renin-angiotensin-aldosterone system, sympathetic nervous system, release of vasopressin), and resistance to vasopressors. The vasodilatory state is mediated through adrenomedullin, calcitonin gene-related peptide, nitric oxide, and other vasodilators, and is most pronounced in the splanchnic area. This constitutes an effective (although relative) counterbalance to increased arterial blood pressure. This review considers the alterations in systemic hemodynamics in patients with cirrhosis in relation to essential hypertension and arterial hypertension of the renal origin. Subjects with arterial hypertension (essential, secondary) may become normotensive during the development of cirrhosis, and arterial hypertension is rarely manifested in patients with cirrhosis, even in cases with renovascular disease and high circulating renin activity. There is much dispute as to the understanding of homoeostatic regulation in cirrhotic patients with manifest arterial hypertension. This most likely includes the combination of vasodilatation and vasoconstriction in parallel. PMID:16521178

  13. The Jamaican hypertension prevalence study.

    PubMed

    Ragoobirsingh, Dalip; McGrowder, Donovan; Morrison, Errol Y; Johnson, Pauline; Lewis-Fuller, Eva; Fray, John

    2002-07-01

    This study was designed to investigate the prevalence of hypertension in Jamaica. Jamaica has an area of 4,411 square miles and is divided into 14 parishes. The visited districts were randomly selected. The sample population was selected based upon a two-stage stratified random sampling design. Each dwelling in the "Sampling Universe" had an equal probability of being selected. The survey team spent a week in the districts in each parish selected. Employing the Statistical Institute of Jamaica's (STATIN) two-stage stratified random sampling design, preselected house-holds were visited. Non-response was documented and considered in the final analysis. Only individuals 15 years and older were allowed to participate in the study. The 2,064 subjects who participated were the basis for estimates of hypertension. Following logistic regression analysis, the main risk factors for hypertension are being female, advancing age, obesity, having diabetes and having a family history of hypertension. Jamaica has a point prevalence of hypertension of 30.8% in the 15-and-over age group. These findings would greatly assist in formulating policies to deal with this scourge of society. PMID:12126281

  14. Avicenna's doctrine about arterial hypertension.

    PubMed

    Emtiazy, Majid; Choopani, Rasool; Khodadoost, Mahmood; Tansaz, Mojgan; Dehghan, Sohrab; Ghahremani, Zeinab

    2014-01-01

    Arterial hypertension is a major risk factor for the development of cardiovascular diseases. Data from observational studies indicate that it may affect 90% of the general population during their lifetime. Despite much research that has been done, the exact cause of this disorder is still unknown. Avicenna (Ibn Sina) in his masterpiece The Canon of Medicine described most of the clinical features, causes, and complications which are consistent with hypertension symptoms based on modern medicine. He described in detail the symptoms of hypertension such as headache, heaviness in the head, sluggish movements, general redness and warm to touch feel of the body, prominent, distended and tense veins, fullness of the pulse, distension of the skin, coloured and dense urine, loss of appetite, weak eye sight, impairment of thinking, yawning, and drowsiness. Moreover, Avicenna described haemorrhage and sudden death as the complications of hypertension. Due to the importance of this issue, we wanted to call the reader's attention to Avicenna's views about what corresponds to hypertension in modern medicine. PMID:25310615

  15. Accelerated Hypertension after Venlafaxine Usage

    PubMed Central

    K?vrak, Yüksel; Güvenç, Tolga Sinan; Akbulut, Nurcihan; Ya?c?, ?brahim; Ç???ar, Gül?en; Gündüz, Süleyman; Balc?, Bahattin

    2014-01-01

    Venlafaxine is the first antidepressant that acts via inhibiting serotonin and noradrenaline reuptake. Hypertension is observed in doses exceeding 300?mg/day and is the most feared complication. We report a patient with accelerated hypertension after venlafaxine use observed at a dose of 150?mg/day. A 23-year-old patient with symptoms of insomnia, depression, anhedonia, fatigue admitted our clinic. Venlafaxine at a dose of 75?mg/day was initiated after he was diagnosed with major depressive disorder. After 5 months, venlafaxine dose was uptitrated to 150?mg/day due to inadequate response to drug. After using venlafaxine for ten months at the dose of 150?mg/day, he admitted our clinic with headache and epistaxis. He was hospitalized after his blood pressure was measured as 210/170?mmHg. No secondary causes for hypertension were found, and venlafaxine treatment was considered possible etiologic factor. After stopping venlafaxine treatment, his blood pressure was reverted back to normal limits. While mild elevation of blood pressure could be observed after venlafaxine treatment, this case shows that accelerated hypertension with a diastolic blood pressure rise above 120?mmHg could be observed at relatively low doses of venlafaxine. Close monitoring of blood pressure is necessary after initiation of treatment, as accelerated hypertension could cause endorgan damage with potentially catastrophic results. PMID:25328745

  16. Prevention of Hypertension, Cardiovascular Damage and Endothelial Dysfunction with Green Tea Extracts

    Microsoft Academic Search

    Michele Antonello; Domenico Montemurro; Massimo Bolognesi; Marco Di Pascoli; Anna Piva; Franco Grego; Daniele Sticchi; Luisa Giuliani; Spiridione Garbisa; Gian Paolo Rossi

    2007-01-01

    Background: We investigated the effect of green tea extract (GTE) in arterial hypertension with high oxidative stress. Angiotensin (Ang) II induces endothelial dysfunction (ED) that is crucial for the development of atherosclerosis and hypertension.Methods: Male Sprague-Dawley rats, 13 weeks old, randomly assigned to drinking water with or without GTE (6 mg\\/mL) received a vehicle, a high (700 ?g\\/kg\\/d) or a

  17. Bosentan in pulmonary arterial hypertension: a comparison between congenital heart disease and chronic pulmonary embolism

    Microsoft Academic Search

    M. G. J. Duffels; M. N. van der Plas; S. Surie; M. M. Winter; B. J. Bouma; M. Groenink; A. P. J. van Dijk; E. S. Hoendermis; R. M. F. Berger; P. Bresser; B. J. M. Mulder

    2009-01-01

    Background. In patients with pulmonary hypertension, it is unknown whether the treatment effect of bosentan is dependent on the duration\\u000a of pulmonary vessel changes. Therefore, we studied the response to bosentan in patients with life-long pulmonary vessel changes\\u000a (pulmonary arterial hypertension (PAH) due to congenital heart disease (CHD)) and in patients with subacutely induced pulmonary\\u000a vessel changes (chronic thromboembolic pulmonary

  18. Carbon monoxide reverses established pulmonary hypertension

    PubMed Central

    Zuckerbraun, Brian S.; Chin, Beek Yoke; Wegiel, Barbara; Billiar, Timothy R.; Czsimadia, Eva; Rao, Jayashree; Shimoda, Larissa; Ifedigbo, Emeka; Kanno, Shin; Otterbein, Leo E.

    2006-01-01

    Pulmonary arterial hypertension (PAH) is an incurable disease characterized by a progressive increase in pulmonary vascular resistance leading to right heart failure. Carbon monoxide (CO) has emerged as a potently protective, homeostatic molecule that prevents the development of vascular disorders when administered prophylactically. The data presented in this paper demonstrate that CO can also act as a therapeutic (i.e., where exposure to CO is initiated after pathology is established). In three rodent models of PAH, a 1 hour/day exposure to CO reverses established PAH and right ventricular hypertrophy, restoring right ventricular and pulmonary arterial pressures, as well as the pulmonary vascular architecture, to near normal. The ability of CO to reverse PAH requires functional endothelial nitric oxide synthase (eNOS/NOS3) and NO generation, as indicated by the inability of CO to reverse chronic hypoxia-induced PAH in eNOS-deficient (nos3?/?) mice versus wild-type mice. The restorative function of CO was associated with a simultaneous increase in apoptosis and decrease in cellular proliferation of vascular smooth muscle cells, which was regulated in part by the endothelial cells in the hypertrophied vessels. In conclusion, these data demonstrate that CO reverses established PAH dependent on NO generation supporting the use of CO clinically to treat pulmonary hypertension. PMID:16908624

  19. Nitric oxide and pulmonary hypertension

    PubMed Central

    2010-01-01

    Pulmonary hypertension is a serious complication of a number of lung and heart diseases that is characterized by peripheral vascular structural remodeling and loss of vascular tone. Nitric oxide can modulate vascular injury and interrupt elevation of pulmonary vascular resistance selectively; however, it can also produce cytotoxic oxygen radicals and exert cytotoxic and antiplatelet effects. The balance between the protective and adverse effects of nitric oxide is determined by the relative amount of nitric oxide and reactive radicals. Nitric oxide has been shown to be clinically effective in the treatment of congenital heart disease, mitrial valvular disease combined with pulmonary hypertension and in orthotropic cardiac transplantation patients. Additionally, new therapeutic modalities for the treatment of pulmonary hypertension, phosphodiesterase inhibitors, natriuretic peptides and aqueous nitric oxide are also effective for treatment of elevated pulmonary vascular resistance. PMID:20498805

  20. Hypertension and cochlear hearing loss.

    PubMed

    Przewo?ny, Tomasz; Gójska-Grymaj?o, Anna; Kwarciany, Mariusz; G?secki, Dariusz; Narkiewicz, Krzysztof

    2015-08-01

    This paper presents a review of experimental and clinical research on the contribution of hypertension to cochlear hearing loss. Hypertension is one of the crucial risk factors underlying pathophysiological processes taking place in the cochlea. Several mechanisms explaining these processes have been described, mainly in animal models, such as the disturbance of the inner ear potassium recycling process due to the detrimental action of natriuretic hormone, and the decrease in the cochlear oxygen partial pressure. Current evidence linking hypertension to sensorineural high-frequency cochlear hearing loss in humans may be confounded by other concomitant diseases or risk factors such as age, coronary artery disease, diabetes, obesity, hyperlipidemia, smoking and noise exposure. Therefore, further research in this field is clearly needed. PMID:26032520

  1. Genetic determinants of hypertension: An update

    Microsoft Academic Search

    Michael Harrison; Karen Maresso; Ulrich Broeckel

    2008-01-01

    Hypertension represents a global public health burden. In addition to the rarer Mendelian forms of hypertension, classic genetic\\u000a studies have documented a significant heritable component to the most common form, essential hypertension (EH). Extensive\\u000a efforts are under way to elucidate the genetic basis of this disease. Recently, a new form of Mendelian hypertension has been\\u000a identified, pharmacogenetic association studies in

  2. Long-Term Magnesium Supplementation in Essential Hypertension

    Microsoft Academic Search

    L. A. Ferrara; R. Iannuzzi; A. Castaldo; A. Iannuzzi; Dello Russo; M. Mancini

    1992-01-01

    The main objective of this clinical trial was to evaluate the effects of magnesium pidolate (15 mmol\\/day) on blood pressure at rest and during sympathetic stimulation induced by cold, isometric and tilt test; peripheral blood flow has been evaluated by strain-gauge plethysmography. Fourteen mild to moderate hypertensives (8 males, 6 females, age range 40-60 years) were randomly given magnesium or

  3. African American hypertensives: Cognition and self care

    Microsoft Academic Search

    Kay Louise Klymko

    2006-01-01

    Problem. While evidence is present supporting aging and hypertension's association with cognitive decline, few, if any, studies have related cognition, self-care, and blood pressure outcomes in African American elders with hypertension. Purpose. The purposes of this study were to: (a) describe types of cognitive functions in elder hypertensive African Americans, (b) test relationships among concepts in a mid-range theory derived

  4. Treatment of Arterial Hypertension in Obese Patients

    Microsoft Academic Search

    U. Wenzel; C. Krebs

    2006-01-01

    The prevalence of obesity is steadily increasing. Hypertension is one of the most common co-morbidities of obesity and significantly contributes to morbidity and mortality. Most obese hypertensive patients require antihypertensive drug treatment. However, current guidelines do not give specific recommendations for antihypertensive therapy of obese hypertensive patient. Some antihypertensive agents may have unwanted effects on the metabolic and hemodynamic abnormalities

  5. Hypertension in Children After Renal Transplantation

    Microsoft Academic Search

    Tomas Seeman

    2007-01-01

    Hypertension is a serious complication in children after renal transplantation, it is an important risk factor not only for graft loss but also for cardiovascular morbidity and mortality of transplanted patients. The etiology of posttrans- plant hypertension is multifactorial - pretransplant hypertension, damaged native kidneys, immunosuppressive therapy (steroids, cyclosporine, tacrolimus), renal graft artery stenosis and chronic allograft nephropathy are the

  6. Chronic hypokalaemia in a hypertensive patient

    PubMed Central

    Luft, Friedrich C.

    2012-01-01

    Hypokalaemia in hypertensive patients is a ‘red flag’ bringing to mind various classic secondary and genetic causes related to both hypokalaemia and hypertension. We encountered a patient who had an unusual cause for his disturbance that, to our knowledge, has not been described in hypertensive patients.

  7. Predictors of stroke pattern in hypertensive patients

    Microsoft Academic Search

    Isabel Lestro Henriques; Julien Bogousslavsky; Guy van Melle

    1996-01-01

    Background and purpose: Hypertension is a recognized risk factor for stroke. However, it is not clear why hypertensive patients may have different types and causes of stroke. Methods: The possible role of coexisting factors was studied in 1057 patients with hypertension and first stroke admitted to a population-based stroke center. We used logistic regression analysis (multivariate and polychotomous) and the

  8. Acute disseminated encephalomyelitis presenting with hypertensive emergency.

    PubMed

    Ganguly, Samrat; Das, Mousumi; Bagchi, Nilay Ranjan

    2014-04-01

    We report a 12-year-old girl presenting with acute disseminated encephalomyelitis (ADEM) along with hypertensive emergency. Hypertension persisted for few weeks following recovery and subsided with oral clonidine. Although autonomic instability in ADEM has been reported before, hypertensive emergency was not previously documented as presenting feature of ADEM. PMID:24327453

  9. The Flavonoid Quercetin Reverses Pulmonary Hypertension in Rats

    PubMed Central

    Moreno, Enrique; Moral-Sanz, Javier; Barreira, Bianca; Galindo, Pilar; Pandolfi, Rachele; Jimenez, Rosario; Moreno, Laura; Cogolludo, Angel; Duarte, Juan; Perez-Vizcaino, Francisco

    2014-01-01

    Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os) or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH. PMID:25460361

  10. Arginase inhibition alleviates hypertension in the metabolic syndrome

    PubMed Central

    El-Bassossy, Hany M; El-Fawal, Rania; Fahmy, Ahmed; Watson, Malcolm L

    2013-01-01

    Background and Purpose We have previously shown that arginase inhibition alleviates hypertension associated with in a diabetic animal model. Here, we investigated the protective effect of arginase inhibition on hypertension in metabolic syndrome. Experimental Approach Metabolic syndrome was induced in rats by administration of fructose (10% in drinking water) for 12 weeks to induce vascular dysfunction. Three arginase inhibitors (citrulline, norvaline and ornithine) were administered daily in the last 6 weeks of study before and tail BP was recorded in conscious animals. Concentration response curves for phenylephrine (PE), KCl and ACh in addition to ACh-induced NO generation were obtained in thoracic aorta rings. Serum glucose, insulin, uric acid and lipid profile were determined as well as reactive oxygen species (ROS) and arginase activity. Key Results Arginase activity was elevated in metabolic syndrome while significantly inhibited by citrulline, norvaline or ornithine treatment. Metabolic syndrome was associated with elevations in systolic and diastolic BP, while arginase inhibition significantly reduced elevations in diastolic and systolic BP. Metabolic syndrome increased vasoconstriction responses of aorta to PE and KCl and decreased vasorelaxation to ACh, while arginase inhibition completely prevented impaired responses to ACh. In addition, arginase inhibition prevented impaired NO generation and exaggerated ROS formation in metabolic syndrome. Furthermore, arginase inhibition significantly reduced hyperinsulinaemia and hypertriglyceridaemia without affecting hyperuricaemia or hypercholesterolaemia associated with metabolic syndrome. Conclusions and Implications Arginase inhibition alleviates hypertension in metabolic syndrome directly through endothelial-dependent relaxation/NO signalling protection and indirectly through inhibition of insulin resistance and hypertriglyceridaemia. PMID:23441715

  11. Chronic infusion of lisinopril into hypothalamic paraventricular nucleus modulates cytokines and attenuates oxidative stress in rostral ventrolateral medulla in hypertension.

    PubMed

    Li, Hong-Bao; Qin, Da-Nian; Ma, Le; Miao, Yu-Wang; Zhang, Dong-Mei; Lu, Yan; Song, Xin-Ai; Zhu, Guo-Qing; Kang, Yu-Ming

    2014-09-01

    The hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play a critical role in the generation and maintenance of sympathetic nerve activity. The renin-angiotensin system (RAS) in the brain is involved in the pathogenesis of hypertension. This study was designed to determine whether inhibition of the angiotensin-converting enzyme (ACE) in the PVN modulates cytokines and attenuates oxidative stress (ROS) in the RVLM, and decreases the blood pressure and sympathetic activity in renovascular hypertensive rats. Renovascular hypertension was induced in male Sprague-Dawley rats by the two-kidney one-clip (2K1C) method. Renovascular hypertensive rats received bilateral PVN infusion with ACE inhibitor lisinopril (LSP, 10?g/h) or vehicle via osmotic minipump for 4weeks. Mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and plasma proinflammatory cytokines (PICs) were significantly increased in renovascular hypertensive rats. The renovascular hypertensive rats also had higher levels of ACE in the PVN, and lower level of interleukin-10 (IL-10) in the RVLM. In addition, the levels of PICs, the chemokine MCP-1, the subunit of NAD(P)H oxidase (gp91(phox)) and ROS in the RVLM were increased in hypertensive rats. PVN treatment with LSP attenuated those changes occurring in renovascular hypertensive rats. Our findings suggest that the beneficial effects of ACE inhibition in the PVN in renovascular hypertension are partly due to modulation cytokines and attenuation oxidative stress in the RVLM. PMID:24937322

  12. DECREASED HEART RATE IS ASSOCIATED WITH CARBAMATE-INDUCED ACTIVATION OF PRO-INFLAMMATORY SERUM PROTEINS.

    EPA Science Inventory

    Previously we reported that chlorpyrifos (CHP), an irreversible cholinesterase (ChE) inhibitor, induces hypertension in rats. Concomitant with hypertension, we found an increase in C-reactive protein, macrophage inflammatory protein-2 , monocyte chemotactic protein-5 and interfer...

  13. Role of Hypertension in Aggravating A? Neuropathology of AD Type and Tau-Mediated Motor Impairment

    PubMed Central

    Díaz-Ruiz, C.; Wang, J.; Ksiezak-Reding, H.; Ho, L.; Qian, X.; Humala, N.; Thomas, S.; Martínez-Martín, P.; Pasinetti, G. M.

    2009-01-01

    Epidemiological evidence suggests that hypertension may accelerate the onset and progression of Alzheimer's disease (AD). In this study, we explored the role of hypertension in the neurodegenerative changes associated with A? and tau aggregation. We induced hypertension in APPswe Tg2576 and P301L-tauTg mouse models. In Tg2576 mice, experimental hypertension was associated with a significant increase of the accumulation of Amyloid-? (A?) peptides in brain tissue and a significant reduction of A? peptides in serum (P < .05). These results indicate that hypertension may promote AD-type A? neuropathology in Tg2576. In P301L-tauTg mice we found that the presence of hypertension was significantly associated with aggravated motor function assessed by hindlimb extension test (P = .01). These results suggest that hypertension may play a role in accelerating the progression of motor dysfunction associated with tau-related alterations. Our studies suggest that the management of blood pressure (BP) may alleviate AD-type A? neuropathology and neurological disorders associated with abnormal tau metabolism. PMID:19936102

  14. Angiotensin-converting enzyme gene polymorphisms and hypertension in occupational noise exposure in Egypt

    PubMed Central

    Zawilla, Nermin; Shaker, Dalia; Abdelaal, Amaal; Aref, Wael

    2014-01-01

    Background: The gene–environment interaction in the pathogenesis of hypertension has not been extensively studied in occupational noise. Objectives: The aim of this study was to determine the relationship between noise and hypertension in Egyptian workers, the interaction of angiotensin-converting enzyme (ACE) gene polymorphisms as modifiers, and the possible relationship between noise hearing impairment and hypertension. Methods: Study subjects were divided into two groups depending on noise exposure level. The control group (n?=?161) was exposed to noise intensity <85 dB and the exposed group (n?=?217) was exposed to noise intensity ?85 dB. A polymerase chain reaction was used to differentiate the various genotypes of ACE insertion/deletion (I/D) and ACE G2350A. Results: Noise significantly increased the likelihood of hypertension. Carriers of the genotypes AG, GG, and DD were vulnerable to hypertension on noise exposure. No association between hypertension and hearing impairment or noise-induced hearing loss (NIHL) was found. Conclusion: Our results support the association between ACE gene polymorphisms and occurrence of hypertension in noise-exposed workers. PMID:25000107

  15. Misconceptions and facts about treating hypertension.

    PubMed

    Argulian, Edgar; Grossman, Ehud; Messerli, Franz H

    2015-05-01

    Hypertension is a powerful risk factor strongly linked to adverse cardiovascular outcomes. Because of its high prevalence, health care providers at many levels are involved in treating hypertension. Distinct progress has been made in improving the rates of hypertension awareness and treatment over years, but the overall control of hypertension remains inadequate. Several recent guidelines from different sources have been put forward in an attempt to bridge the gap between existing evidence and clinical practice. Despite this effort, several misconceptions about treating hypertensive cardiovascular disease continue to persist among clinicians. This review highlights some of the misconceptions regarding antihypertensive therapy. PMID:25486449

  16. Role of magnesium in hypertension

    Microsoft Academic Search

    Bruno Sontia; Rhian M. Touyz

    2007-01-01

    Magnesium affects blood pressure by modulating vascular tone and reactivity. It acts as a calcium channel antagonist, it stimulates production of vasodilator prostacyclins and nitric oxide and it alters vascular responses to vasoactive agonists. Magnesium deficiency has been implicated in the pathogenesis of hypertension with epidemiological and experimental studies demonstrating an inverse correlation between blood pressure and serum magnesium levels.

  17. Classification of hypertension in pregnancy

    Microsoft Academic Search

    Mark A. Brown; Michael de Swiet

    1999-01-01

    In many ways there should be no need to classify hypertensive disorders in clinical practice. The very presence of rising blood pressure should alert the clinician to seek evidence for the development of pre-eclampsia and whether there are any emerging abnormalities of fetal growth and\\/or maternal renal, cerebral, hepatic or coagulation functions which may necessitate specific treatment, including delivery. While

  18. Body fluid compartments in hypertension

    Microsoft Academic Search

    R. CIANCI; F. CITRO; A. MIGNECO; F. BALDONI; M. C. MINISCI; N. DI DANIELE; A. DE LORENZO; Tor Vergata

    2006-01-01

    Background and Objec- tives: There is a correlation between the fluid and ionic homeostasis and blood pressure but it is not known if these body fluid changes rep- resent the cause or rather the effect of the blood pressure rise. We have estimated the compartmental distribution of body fluids by means of the Bioimpedance Spectroscopy (BIS) analysis in a hypertensive

  19. Genes and Pulmonary Arterial Hypertension

    Microsoft Academic Search

    Benjamin Sztrymf; Azzedine Yaďci; Barbara Girerd; Marc Humbert

    2007-01-01

    Familial pulmonary arterial hypertension (FPAH) was first described more than 50 years ago. Before the availability of modern genetic tools, studies of the genealogies demonstrated that these cases segregated as an autosomic dominant trait, with an incomplete penetrance and a genetic anticipation phenomenon by which age at onset of the disease is decreasing in the subsequent generations. Germline mutations in

  20. Arterial hemodynamics in human hypertension.

    PubMed

    Ting, C T; Brin, K P; Lin, S J; Wang, S P; Chang, M S; Chiang, B N; Yin, F C

    1986-12-01

    Differences in aortic impedance between normotensives and hypertensives are not well characterized. We examined impedance in 8 normotensive and 11 hypertensive (mean 96.7 vs. 122.2 mmHg) age-matched, Chinese patients undergoing cardiac catheterization at rest, during nitroprusside, and handgrip exercise before and after beta blockade (propranolol). Hypertensives had higher resistance (2,295 vs. 1713 dyn-s/cm5), characteristic impedance (145.7 vs. 93.9 dyn-s/cm5), total external power (1,579 vs. 1174 mW), peripheral reflections (ratio of backward to forward wave components of 0.54 vs. 0.44), and first zero crossing of impedance phase angle (4.15 vs. 2.97 Hz). These abnormalities were eliminated with vasodilatation. Differences between groups were not further exacerbated when pressure was increased during handgrip exercise. Beta blockade further increased resistance and reflections. Thus, hemodynamic abnormalities of essential hypertension (increased resistance, reflections, and pulse wave velocity, and decreased compliance) are compatible with an increased vasomotor tone that is further unmasked during generalized beta blockade. PMID:3782467

  1. Aminopeptidase N in arterial hypertension.

    PubMed

    Danziger, Robert S

    2008-09-01

    Aminopeptidase N (APN) or CD13 is a conserved type II integral membrane zinc-dependent metalloprotease in the M1 family of ectoenzymes. APN is abundant in the kidneys and central nervous system. Identified substrates include Angiotensin III (Ang III); neuropeptides, including enkephalins and endorphins; and homones, including kallidan and somatostatin. It is developmentally expressed, a myelomonocytic marker for leukemias, and a receptor for coronovirus. There is evolving support for APN in the regulation of arterial blood pressure and the pathogenesis of hypertension. In rodent strains, intracerebraventricular (i.c.v.) infusions of APN reduces, while inhibitors of APN activity have a pressor effect on blood pressure. Dysregulation of central APN has been linked to the pathogenesis of hypertension in the spontaneously hypertensive rat. There is evidence that renal tubule APN inhibits Na flux and plays a mechanistic role in salt-adaptation. A functional polymorphism of the ANP gene has been identified in the Dahl salt-sensitive rat. Signaling by APN impacting on blood pressure is likely mediated by regulation of the metabolism of Ang III to Ang IV. Whether APN regulates arterial blood pressure in humans or is a therapeutic target for hypertension are subjects for future exploration. PMID:18008160

  2. [The best of hypertension 2005].

    PubMed

    Chamontin, B

    2006-01-01

    In 2005, new data on the prognostic value of blood pressure measurement in the home and by ambulatory recordings were published from the Italian (PAMELA) and Japanese (OHASAMA) registers. The ambulatory BP has a greater prognostic value than that measured in the physician's office in hypertensive patients whereas the difference in prognostic value is less in normotensive patients. The prevalence of masked hypertension is estimated at 15 to 26% with reference to the diastolic and systolic BP. The cardiovascular risk is significantly higher in patients with permanent or masked hypertension compared with normotensive subjects and "white coat" hypertensive patients. The ASCOT trial showed that in primary prevention of hypotensive patients with more than 3 associated cardiovascular risk factors, a strategy based on amlodipine secondarily associated with a diuretic, provided better control of the blood pressure than that of a betablocker secondarily associated with a diuretic: the therapeutic trial was negative with respect to the primary criterion including fatal coronary events and non-fatal myocardial infarction but the trial was stopped prematurely because of a significant reduction in cardiovascular and global mortality in the amlodipine-perindopril arm compared with the atenolol-thiazide arm. The metaregression of Verdecchia confirmed that the reduction of the BP remains the essential beneficial factor of antihypertensive therapy, but suggested that; in addition to the reduction of the blood pressure, ACE inhibitors provided better protection against coronary disease than calcium antagonists whereas the calcium antagonists were superior to ACE inhibitors for prevention of stroke. The endothelium is confirmed as a potential therapeutic target. Endothelial dysfunction has been demonstrated in resistance and conduction vessels. The study of antihypertensive therapy on endothelial vasodilation is a new pharmacological approach which may help differentiate the benefits of different classes. New data has documented the relations between inflammation, the vessel and hypertension, and different cytokines hs-CRP, ICAM1, IL6, TNF alpha and MCP-1 may be implicated. The new HAS 2005 recommendations for the management of adult hypertensive patients have been published recently; they are an updated reference for the optimisation of treatment in everyday clinical practice in France. The value of auto-measurement and ambulatory BP recording, the necessary estimation of global cardiovascular risk, the use of the 5 classes of antihypertensive drugs having shown a reduction in cardiovascular morbid-mortality, constitute the key points of these recommendations. Finally, data is now available concerning the incidence of hypertension in France in a working population (IPHAF study) and is estimated at 3% in men and 1.34% in women. PMID:16479962

  3. Impedance Cardiographic (ICG) Assessment of Pregnant Women With Severe Hypertension to Assess Impact of Standard Therapy

    ClinicalTrials.gov

    2013-12-11

    Pregnancy; Proteinuria, With Hypertension (Severe Pre-eclampsia); Delivery; Proteinuria, With Gestational Hypertension (Pre-eclampsia, Severe); Pregnancy; Hypertension, Gestational Hypertension, With Albuminuria (Severe Pre-eclampsia)

  4. Characterization and Treatment of Resistant Hypertension

    PubMed Central

    Pisoni, Roberto; Ahmed, Mustafa I.; Calhoun, David A.

    2010-01-01

    Resistant hypertension is a common medical problem and carries a significantly increased risk of end organ damage and cardiovascular events as compared with more easily controlled hypertension. Resistant hypertension is most often related to isolated systolic hypertension and is characterized by aldosterone excess and increased intravascular volume. Its diagnosis requires the exclusion of pseudoresistance. The etiology of resistant hypertension is almost always multifactorial and common reversible contributing factors need to be identified and addressed. Secondary causes of hypertension such as primary aldosteronism, parenchymal and vascular kidney disease, and obstructive sleep apnea require investigation and effective treatment if present. Therapy for resistant hypertension should be based on use of rational drug class combinations at optimal doses with particular attention to adequate diuretic use. The addition of an aldosterone antagonist may further improve blood pressure control. PMID:19863864

  5. HYPERTENSION TELEMANAGEMENT IN AFRICAN AMERICANS

    PubMed Central

    Finkelstein, Joseph; Cha, Eunme

    2009-01-01

    Background We propose evaluation of a multi-component home automated telemanagement (HAT) system providing integrated support to both clinicians and patients in implementing hypertension treatment guidelines. Methods In a randomized clinical study 550 African Americans with hypertension are followed for 18 months. The major components of the intervention and control groups are identical and are based on the current standard of care. For the purpose of this study, we define “standard of care” as the expected evidence-based care provided according to the current hypertension treatment guidelines. While intervention and control groups are similar in terms of their care components, they differ in the mode of care delivery. For the control group the best attempt is made to deliver all components of a guideline-concordant care in a routine clinical environment whereas for the intervention group the routine clinical environment is enhanced with Health Information Technology (IT) that assists clinicians and patients in working together in implementing treatment guidelines. The HAT system guides patients in following their individualized treatment plans and helps care coordination team in monitoring the patient progress. The study design is aimed at addressing the main question of this trial: whether the addition of the IT-enhanced care coordination in the routine primary care setting can improve delivery of evidence-based hypertension care in African Americans. The outcome parameters include quality of life, medical care utilization, treatment compliance, psychosocial variables and improvement in blood pressure control rates. Conclusions The trial will provide insight on the potential impact of IT-enhanced care coordination in African Americans with poorly controlled hypertension. PMID:20031848

  6. Protective effects of grape seed proanthocyanidins on cardiovascular remodeling in DOCA-salt hypertension rats.

    PubMed

    Huang, Ling-Ling; Pan, Chen; Wang, Li; Ding, Ling; Guo, Kun; Wang, Hong-Zhi; Xu, A-Man; Gao, Shan

    2015-08-01

    Cardiovascular remodeling, as a hallmark of hypertension-induced pathophysiology, causes substantial cardiovascular morbidity and mortality. There is increasing evidence that has demonstrated a broad spectrum of pharmacological and therapeutic benefits of grape seed proanthocyanidins (GSP) against oxidative stress and cardiovascular diseases. In this study, 180- to 200-g SD rats treated with DOCA (120 mg/week sc with 1% NaCl and 0.2% KCl in drinking water) and GSP (150, 240, 384 mg/kg) or amlodipine (ALM) (5 mg/kg) for 4 weeks were recruited. The protective effects of GSP on blood pressure and cardiovascular remodeling in rats with DOCA-salt-induced hypertension were investigated. Our results indicated that DOCA-salt could induce hypertension, cardiovascular remodeling and dysfunction, oxidative stress and the release of endothelin-1 (ET-1) and could increase JNK1/2 and p38MAPK phosphorylation. GSP or ALM treatments significantly improved hypertension, cardiovascular remodeling and dysfunction and oxidative stress, restrained the release of ET-1 and down-regulated the JNK1/2 and p38MAPK phosphorylation. These findings demonstrate that GSP has protective effects against increase of blood pressure induced by DOCA-salt hypertension and cardiovascular remodeling by inhibiting the reactive oxygen species/mitogen-activated protein kinase pathway via restraining the release of ET-1. PMID:25937175

  7. Genetic control of renal thiazide receptor response to dietary NaCl and hypertension.

    PubMed

    Fanestil, D D; Vaughn, D A; Hyde, R H; Blakely, P

    1999-03-01

    Excess NaCl increases blood pressure in some strains of animals but not others. An 8% NaCl diet did not change renal thiazide receptor (TZR) density in two salt-resistant normotensive rat strains (Wistar-Kyoto and Sprague-Dawley) [Fanestil, D. D., D. A. Vaughn, and P. Blakely. Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R1241-R1245, 1997]. However, the renal response to salt differs in normal and hypertensive kidneys [Rettig, R., N. Bandelow, O. Patschan, B. Kuttler, B. Frey, and A. Uber. J. Hum. Hypertens. 10: 641-644, 1996]. Therefore, we examined two strains with salt-aggravated hypertension. Renal TZR did not change when Dahl-S (salt sensitive) animals became hypertensive with 8% dietary NaCl. In contrast, renal TZR decreased 34%, whereas blood pressure increased further, in SHR with 8% dietary NaCl. Blood pressure increased after NG-nitro-L-arginine in SHR, but renal TZR did not change, indicating the salt-induced decrease in TZR in SHR cannot be attributed nonspecifically to elevated arterial pressure. We conclude that the renal response to NaCl-induced increases in blood pressure can be genetically modulated independently of the genes that mediate either the primary hypertension or the salt sensitivity of the hypertension. This finding may be of use in future studies directed at identifying genotypes associated with salt-dependent hypertension. PMID:10070153

  8. Chronic Hypertension Leads to Neurodegeneration in the TgSwDI Mouse Model of Alzheimer's Disease.

    PubMed

    Kruyer, Anna; Soplop, Nadine; Strickland, Sidney; Norris, Erin H

    2015-07-01

    Numerous epidemiological studies link vascular disorders, such as hypertension, diabetes mellitus, and stroke, with Alzheimer's disease (AD). Hypertension, specifically, is an important modifiable risk factor for late-onset AD. To examine the link between midlife hypertension and the onset of AD later in life, we chemically induced chronic hypertension in the TgSwDI mouse model of AD in early adulthood. Hypertension accelerated cognitive deficits in the Barnes maze test (P<0.05 after 3 months of treatment; P<0.001 after 6 months), microvascular deposition of ?-amyloid (P<0.001 after 3 months of treatment; P<0.05 after 6 months), vascular inflammation (P<0.05 in the dentate gyrus and P<0.001 in the dorsal subiculum after 6 months of treatment), blood-brain barrier leakage (P<0.05 after 3 and 6 months of treatment), and pericyte loss (P<0.05 in the dentate gyrus and P<0.01 in the dorsal subiculum after 6 months of treatment) in these mice. In addition, hypertension induced hippocampal neurodegeneration at an early age in this mouse line (43% reduction in the dorsal subiculum; P<0.05), establishing this as a useful research model of AD with mixed vascular and amyloid pathologies. PMID:25941345

  9. Purinergic receptors in tubulointerstitial inflammatory cells: a pathophysiological mechanism of salt-sensitive hypertension.

    PubMed

    Franco, M; Bautista-Pérez, R; Pérez-Méndez, O

    2015-05-01

    Recent studies have suggested that both the tubulointerstitial inflammatory cells and the activation of purinergic receptors integrate common mechanisms that result in salt-sensitive hypertension. The basis of this hypothesis is that renal endothelial cells release ATP in response to shear stress in the setting of hypertension. It has been demonstrated that the over-expression and activation of the P2X7, P2Y12 and P2X1 receptors favour the elevation of blood pressure induced by high-salt intake. In addition, the release of interleukins and inflammatory mediators in the tubulointerstitial area appears to be related to the activation of these receptors. Renal vasoconstriction and tubulointerstitial injury develop as a result, which increase sodium reabsorption by epithelial cells. Consistent with these effects, the reduction of tubulointerstitial inflammation caused by immunosuppressants, such as mycophenolate mofetil, prevents the development of salt-sensitive hypertension. Also, P2X7-receptor knockout mice develop minor renal injury when hypertension is induced via the administration of deoxycorticosterone acetate and a high-salt diet. In the setting of angiotensin II-induced hypertension, which is an early stage in the development of salt-sensitive hypertension, an acute blockade with the specific, non-selective P2 antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid prevented the renal vasoconstriction induced by angiotensin II. In addition, it normalized glomerular haemodynamics and restored sodium excretion to control values. These findings suggest that chronic administration of P2 purinergic antagonists may prevent the deleterious effects of purinergic receptors during the development of salt-sensitive hypertension. PMID:25683649

  10. Obstructive sleep apnea syndrome (OSAS) and hypertension: Pathogenic mechanisms and possible therapeutic approaches

    PubMed Central

    Zhang, Wang

    2012-01-01

    Obstructive sleep apnea syndrome (OSAS), a chronic condition characterized by collapse of the pharynx during sleep, has been increasingly recognized as a health issue of growing importance over the last decade. Recently emerging evidence suggests that there is a causal link between OSAS and hypertension, and hypertension represents an independent risk factor in OSAS patients. However, the pathophysiological basis for patients with OSAS having an increased risk for hypertension remains to be elucidated. The main acute physiological outcomes of OSAS are intermittent hypoxia, intrapleural pressure changes, and arousal from sleep, which might induce endothelial dysfunction, sympathetic activation, renin–angiotensin–aldosterone system activation, lipid metabolism dysfunction, and increased oxidative stress. This brief review focuses on the current understanding of the complex association between OSAS and hypertension. PMID:23009224

  11. Reduced sodium concentration and increased sodium-potassium pump activity of erythrocytes in human hypertension

    SciTech Connect

    Simon, G.; Engel, C.R.

    1987-06-01

    Erythrocyte Nai, Nai/Ki and ouabain-sensitive and ouabain-insensitive /sup 86/Rb uptake (K transport) were measured in whole blood of 16 normotensive and 19 hypertensive white male subjects, within seconds or minutes after withdrawal of blood. Erythrocyte Nai and Nai/Ki were reduced (p less than 0.05), and ouabain-sensitive /sup 86/Rb uptake was increased (p less than 0.01) in hypertensive subjects. In a separate group of hypertensive white male subjects, an inverse correlation was found between erythrocyte Nai/Ki and ouabain-binding sites per erythrocyte (r = 0.85, p less than 0.01, n = 9). The abnormalities of erythrocyte cation fluxes in hypertensive subjects are similar to those induced by aldosterone in vascular smooth muscle cells and by glucocorticoid administration in the erythrocytes of human subjects, suggesting similarities in pathogenesis.

  12. Kidney Fibrosis in Hypertensive Rats: Role of Oxidative Stress

    PubMed Central

    Zhao, Wenyuan; Chen, Sue S.; Chen, Yuanjian; Ahokas, Robert A.; Sun, Yao

    2008-01-01

    Fibrosis of the glomerulus and the tubulointerstitium occurs in patients with hypertension. Studies have shown that renal oxidative stress appears in hypertensive kidney disease. The potential role of oxidative stress in renal fibrogenesis remains to be elucidated. Herein, we tested the hypothesis that oxidative stress contributes to the development of renal fibrosis during hypertension. Sprague-Dawley rats received angiotensin II (AngII; 9 ?g/h s.c.) for 4 weeks with/without co-treatment of antioxidants, apocynin and tempol (120 mg/kg/day each, p.o.). Untreated rats served as controls. Appearance of renal oxidative stress and its effect on the expression of transforming growth factor (TGF)-ß1, population of myofibroblasts, collagen synthesis/degradation and fibrosis in kidneys were examined. Chronic AngII infusion elevated systemic blood pressure (228 ± 6 mm Hg), which was accompanied with extensive renal fibrosis and oxidative stress represented as upregulated NADPH oxidase and suppressed superoxide dismutase (SOD). Co-treatment with antioxidants led to: (1) markedly decreased renal NADPH oxidase; (2) significantly attenuated gene expression of TGF-ß1, type I collagen, and tissue inhibitors of matrix metalloproteinase (TIMP)-I/-II in the kidney; (3) largely reduced population of myofibroblasts in both the cortex and medulla; (4) significantly reduced renal collagen volume, and (5) partially suppressed blood pressure (190 ± 8 mm Hg). Thus, prolonged AngII administration promotes renal oxidative stress, which is associated with hypertensive renal disease. AngII induces renal oxidative stress by increasing NADPH oxidase and reducing SOD in the kidney, which, in turn, upregulates collagen synthesis, while suppressing collagen degradation, thereby promoting the development of fibrosis in kidneys of hypertensive rats. PMID:18239381

  13. Brain ACE2 overexpression reduces DOCA-salt hypertension independently of endoplasmic reticulum stress.

    PubMed

    Xia, Huijing; de Queiroz, Thyago Moreira; Sriramula, Srinivas; Feng, Yumei; Johnson, Tanya; Mungrue, Imran N; Lazartigues, Eric

    2015-03-01

    Endoplasmic reticulum (ER) stress was previously reported to contribute to neurogenic hypertension while neuronal angiotensin-converting enzyme type 2 (ACE2) overexpression blunts the disease. To assess which brain regions are important for ACE2 beneficial effects and the contribution of ER stress to neurogenic hypertension, we first used transgenic mice harboring a floxed neuronal hACE2 transgene (SL) and tested the impact of hACE2 knockdown in the subfornical organ (SFO) and paraventricular nucleus (PVN) on deoxycorticosterone acetate (DOCA)-salt hypertension. SL and nontransgenic (NT) mice underwent DOCA-salt or sham treatment while infected with an adenoassociated virus (AAV) encoding Cre recombinase (AAV-Cre) or a control virus (AAV-green fluorescent protein) to the SFO or PVN. DOCA-salt-induced hypertension was reduced in SL mice, with hACE2 overexpression in the brain. This reduction was only partially blunted by knockdown of hACE2 in the SFO or PVN, suggesting that both regions are involved but not essential for ACE2 regulation of blood pressure (BP). DOCA-salt treatment did not increase the protein levels of ER stress and autophagy markers in NT mice, despite a significant increase in BP. In addition, these markers were not affected by hACE2 overexpression in the brain, despite a significant reduction of hypertension in SL mice. To further assess the role of ER stress in neurogenic hypertension, NT mice were infused intracerebroventricularlly with tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, during DOCA-salt treatment. However, TUDCA infusion failed to blunt the development of hypertension in NT mice. Our data suggest that brain ER stress does not contribute to DOCA-salt hypertension and that ACE2 blunts neurogenic hypertension independently of ER stress. PMID:25519733

  14. Emergency management of hypertension in children.

    PubMed

    Singh, Dinesh; Akingbola, Olugbenga; Yosypiv, Ihor; El-Dahr, Samir

    2012-01-01

    Systemic arterial hypertension in children has traditionally been thought to be secondary in origin. Increased incidence of risk factors like obesity, sedentary life-styles, and faulty dietary habits has led to increased prevalence of the primary arterial hypertension (PAH), particularly in adolescent age children. PAH has become a global epidemic worldwide imposing huge economic constraint on health care. Sudden acute increase in systolic and diastolic blood pressure can lead to hypertensive crisis. While it generally pertains to secondary hypertension, occurrence of hypertensive crisis in PAH is however rare in children. Hypertensive crisis has been further subclassified depending on presence or absence of end-organ damage into hypertensive emergency or urgency. Both hypertensive emergencies and urgencies are known to cause significant morbidity and mortality. Increasing awareness among the physicians, targeted at investigation of the pathophysiology of hypertension and its complications, better screening methods, generation, and implementation of novel treatment modalities will impact overall outcomes. In this paper, we discuss the etiology, pathogenesis, and management of hypertensive crisis in children. An extensive database search using keywords was done to obtain the information. PMID:22577545

  15. Hypertensive Retinopathy and Risk of Stroke

    PubMed Central

    Ong, Yi-Ting; Wong, Tien Y.; Klein, Ronald; Klein, Barbara E.K.; Mitchell, Paul; Sharrett, A. Richey; Couper, David J.; Ikram, M. Kamran

    2014-01-01

    Although assessment of hypertensive retinopathy signs has been recommended for determining end-organ damage and stratifying vascular risk in hypertensive persons, its value remains unclear. In this study, we examine whether hypertensive retinopathy predicts the long-term risk of stroke in hypertensives. A total of 2907 hypertensive participants aged 50–73 at the 1993–1995 examination, who had gradable retinal photographs, no history of diabetes, stroke and coronary heart disease at baseline and data on incident stroke were included from the Atherosclerosis Risk in Communities (ARIC) Study. Retinal photographs were assessed for hypertensive retinopathy signs and classified as none, mild, and moderate/severe. Incident events of any stroke, cerebral infarction and hemorrhagic stroke were identified and validated. After a mean follow-up period of 13.0 years, 165 persons developed incident stroke (146 cerebral infarctions and 15 hemorrhagic strokes). After adjusting for age, sex, blood pressure, and other risk factors, persons with moderate hypertensive retinopathy were more likely to have stroke (multivariable hazard ratios (HR), moderate versus no retinopathy: 2.37, 95%CI 1.39-4.02). In hypertensives on medication with good control of blood pressure, hypertensive retinopathy was related to an increased risk of cerebral infarction (HR, mild retinopathy: 1.96, 95%CI 1.09-3.55; moderate retinopathy: 2.98, 95%CI 1.01-8.83). Hypertensive retinopathy predicts the long-term risk of stroke, independent of blood pressure, even in treated hypertensives with good hypertension control. Retinal photographic assessment of hypertensive retinopathy signs may be useful for assessment of stroke risk. PMID:23940194

  16. Hypertension Management and Microvascular Insulin Resistance in Diabetes

    PubMed Central

    Ko, Seung-Hyun; Cao, Wenhong; Liu, Zhenqi

    2011-01-01

    Type 2 diabetes is in essence a vascular disease and is frequently associated with hypertension, macrovascular events, and microvascular complications. Microvascular dysfunction, including impaired recruitment and capillary rarefaction, has been implicated in the pathogenesis of diabetic complications. Microvascular insulin resistance and renin-angiotensin system upregulation are present in diabetes, and each contributes to the development of hypertension and microvascular dysfunction. In the insulin-sensitive state, insulin increases microvascular perfusion by increasing endothelial nitric oxide production, but this effect is abolished by insulin resistance. Angiotensin II, acting via the type 1 receptors, induces inflammation and oxidative stress, leading to impaired insulin signaling, reduced nitric oxide availability, and vasoconstriction. Conversely, it acts on the type 2 receptors to cause vasodilatation. Because substrate and hormonal exchanges occur in the microvasculature, antihypertensive agents targeted to improve microvascular insulin sensitivity and function may have beneficial effects beyond their capacity to lower blood pressure in patients with diabetes. PMID:20582734

  17. Epidemiology, pathophysiology, and treatment of hypertension in ischaemic stroke patients.

    PubMed

    Hisham, Nur Fatirul; Bayraktutan, Ulvi

    2013-10-01

    Stroke continues to be one of the leading causes of mortality and morbidity worldwide. There are 2 main types of stroke: ischaemic strokes, which are caused by obstruction of the blood vessels leading to or within the brain, and haemorrhagic strokes, which are induced by the disruption of blood vessels. Stroke is a disease of multifactorial aetiology that may develop as an end state in patients with serious vascular conditions--most notably, uncontrolled arterial hypertension--thereby necessitating the effective control of this risk factor to prevent stroke or its recurrence. This paper focuses specifically on the epidemiology and pathogenesis of ischaemic stroke mainly in chronically hypertensive patients and pays particular attention to the efficacy of a select group of routinely used major antihypertensive drugs (i.e., angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers, and calcium channel blockers) in the treatment of strokes. PMID:22682972

  18. Alkaloids of Nitraria sibirica Pall. decrease hypertension and albuminuria in angiotensin II-salt hypertension.

    PubMed

    Bakri, Mahinur; Yi, Yang; Chen, Ling-Dan; Aisa, Haji Akber; Wang, Mong-Heng

    2014-04-01

    In traditional Chinese medicine, Nitraria sibirica Pall. (Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica (NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Adult mice were divided into three groups: control; infused with angiotensin II and fed a diet containing 4% NaCl (ANG/HS; and ANG/HS plus injection of NSTA (1 mg·kg(-1)·d(-1), i.p.). After treatment of these regimens, daily water and food intake, kidney weight, blood pressure, urinary albumin excretion, renal concentrations of inflammatory markers, including soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and the expression of renal fibrosis markers were determined. Compared to the control group, the ANG/HS group had higher blood pressure and urinary albumin excretion. Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1, as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers. Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers. PMID:24863351

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

    PubMed

    Boueiz, Adel; Hassoun, Paul M

    2014-07-01

    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

  20. Portal circulation and portal hypertension.

    PubMed Central

    Sherlock, S

    1978-01-01

    During the last 25 years, there have been important developments in visualising the portal vein, in examining its contents, and in measuring the pressure of blood flowing within it. Radiologists have set the scene and now is the time of the scanner. These technical advances have been applied to the diagnosis and treatment of patients with portal hypertension, and many ingenious surgical techniques have been proposed. The problem of successful treatment of the patient with bleeding oesophageal varices and cirrhosis of the liver, however, has not yet been solved. This report discusses the portal vein in terms of pressure, flow, and regeneration factors. Portal hypertension is classified and methods of relief are discussed. PMID:342361

  1. [Martorell Hypertensive Ischaemic Leg Ulcer.

    PubMed

    Nobbe, S; Hafner, J

    2014-10-21

    Martorell hypertensive ischaemic leg ulcer (HYTILU) represents an important differential diagnosis of painful leg ulcerations. Stenotic subcutaneous arteriolosclerosis in patients with long-standing arterial hypertension finally leads to skin infarction. The typical histological changes are very similar in Martorell HYTILU and calciphylaxis. This raises the hypothesis that the two entities may have a common pathogenesis. Martorell HYTILU presents as an extremely painful ulcer that is regularly located at the laterodorsal lower leg or at the Achilles tendon. Because of its inflammatory and violaceous wound edges and its tendency to progression, clinicians unaware of the diagnosis Martorell HYTILU might misdiagnose pyoderma gangrenosum or necrotising cutaneous vasculitis start an immunosuppressive treatment and avoid surgical diagnostic and therapeutic procedures. Instead, necrosectomy and split skin grafting are the treatment of choice for Martorell HYTILU. PMID:25333521

  2. Hypertension control in the elderly.

    PubMed

    Neutel, Joel M; Gilderman, Lawrence I

    2008-01-01

    Hypertension is highly prevalent in older persons and most often presents as isolated systolic hypertension. Systolic blood pressure (BP) is a stronger predictor of risk than diastolic BP in persons older than 50 years. Most of these patients will require multiple drug therapies to achieve the substantial reductions in systolic BP needed to reach target levels. Clinical trials have demonstrated that antihypertensive therapy with beta-blockers and diuretics as well as with calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II type 1 receptor blockers reduces cardiovascular risk in older patients. Studies examining safety and BP-lowering efficacy have shown that a renin-angiotensin-aldosterone system blocker plus a calcium channel blocker as well as a combination of diuretics and beta-blockers or diuretics plus an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker achieves greater BP reductions than monotherapy. Such multiple drug regimens are well tolerated in older patients. PMID:18174782

  3. Non-cirrhotic portal hypertension.

    PubMed

    Sarin, Shiv K; Khanna, Rajeev

    2014-05-01

    Non-cirrhotic portal hypertension (NCPH) encompasses a wide range of disorders, primarily vascular in origin, presenting with portal hypertension (PHT), but with preserved liver synthetic functions and near normal hepatic venous pressure gradient (HVPG). Non-cirrhotic portal fibrosis/Idiopathic PHT (NCPF/IPH) and extrahepatic portal venous obstruction (EHPVO) are two prototype disorders in the category. Etiopathogenesis in both of them centers on infections and prothrombotic states. Presentation and management strategies focus on repeated well tolerated episodes of variceal bleed and moderate to massive splenomegaly and other features of PHT. While the long-term prognosis is generally good in NCPF, portal biliopathy and parenchymal extinction after prolonged PHT makes outcome somewhat less favorable in EHPVO. While hepatic schistosomiasis, congenital hepatic fibrosis and nodular regenerative hyperplasia have their distinctive features, they often present with NCPH. PMID:24679506

  4. [Psychological approaches in hypertension management].

    PubMed

    Abgrall-Barbry, Gaëlle; Consoli, Silla M

    2006-06-01

    Stress factors, especially high levels of occupational stress, are associated with hypertension. Several so-called psychological techniques have been applied to hypertension: biofeedback, relaxation techniques (Schultz' autogenic training, Jacobson's progressive relaxation), transcendental meditation, and cognitive behavioral techniques for stress management. Randomized studies show that the best results come from cognitive behavioral methods, whether or not they include relaxation techniques. Other forms of psychotherapy (such as psychoanalysis) may be useful, although their benefits for blood pressure have not been tested in controlled trials. Patients should be informed about the personal benefits they may obtain from psychological treatment. Indications are hyperreactivity to stress, high levels of occupational stress, and difficulty in tolerating or complying with antihypertensive drugs. PMID:16783278

  5. Inhaled Therapies for Pulmonary Hypertension.

    PubMed

    Hill, Nicholas S; Preston, Ioana R; Roberts, Kari E

    2015-06-01

    The inhaled route has a number of attractive features for treatment of pulmonary hypertension, including delivery of drug directly to the target organ, thus enhancing pulmonary specificity and reducing systemic adverse effects. It can also improve ventilation/perfusion matching by dilating vessels supplying ventilated regions, thus improving gas exchange. Furthermore, it can achieve higher local drug concentrations at a lower overall dose, potentially reducing drug cost. Accordingly, a number of inhaled agents have been developed to treat pulmonary hypertension. Most in current use are prostacyclins, including epoprostenol, which has been cleared for intravenous applications but is used off-label in acute care settings as a continuously nebulized medication. Aerosolized iloprost and treprostinil are both prostacyclins that have been cleared by the FDA to treat pulmonary arterial hypertension (PAH). Both require frequent administration (6 and 4 times daily, respectively), and both have a tendency to cause airway symptoms, including cough and wheeze, which can lead to intolerance. These agents cannot be used to substitute for the infused routes of prostacyclin because they do not permit delivery of medication at high doses. Inhaled nitric oxide (INO) is cleared for the treatment of primary pulmonary hypertension in newborns. It is also used off-label to test acute vasoreactivity in PAH during right-heart catheterization and to treat acute right-heart failure in hospitalized patients. In addition, some studies on long-term application of INO either have been recently completed with results pending or are under consideration. In the future, because of its inherent advantages in targeting the lung, the inhaled route is likely to be tested using a variety of small molecules that show promise as PAH therapies. PMID:26070575

  6. Inflammation and Therapy for Hypertension

    Microsoft Academic Search

    Cheryl L. Laffer; Fernando Elijovich

    2010-01-01

    It is currently accepted that hypertension, atherosclerosis, and diabetes are disorders with subtle or overt activation of\\u000a inflammatory mediators. Therefore, it has become increasingly important to ascertain whether current antihypertensive drug\\u000a families have proinflammatory or anti-inflammatory actions that modify the outcomes of their hemodynamic effects on blood\\u000a pressure. We review the current state of knowledge about the effects of the

  7. Endothelial dysfunction in pulmonary hypertension

    Microsoft Academic Search

    Dominique Yelle; Lakshmi Kugathasan; Robin E. MacLaren; Duncan J. Stewart

    \\u000a Pulmonary arterial hypertension (PAH) is a rare disease caused by functional and structural abnormalities in distal pulmonary\\u000a arterioles that result in progressive increases in pulmonary vascular resistance, often leading to right heart failure and\\u000a death. Endothelial dysfunction, defined as a shift in the balance of production of endothelial vasodilator factors (i.e.,\\u000a nitric oxide and prostacyclin), and vasoconstrictor and proliferative factors

  8. Echocardiography in Pediatric Pulmonary Hypertension

    PubMed Central

    Jone, Pei-Ni; Ivy, D. Dunbar

    2014-01-01

    Pulmonary hypertension (PH) can be a rapidly progressive and fatal disease. Although right heart catheterization remains the gold standard in evaluation of PH, echocardiography remains an important tool in screening, diagnosing, evaluating, and following these patients. In this article, we will review the important echocardiographic parameters of the right heart in evaluating its anatomy, hemodynamic assessment, systolic, and diastolic function in children with PH. PMID:25429362

  9. HIV-Related Pulmonary Hypertension

    Microsoft Academic Search

    ATIKUN LIMSUKON; ALI IMRAN SAEED; VIMALA RAMASAMY; JHANSI NALAMATI; SUNIL DHUPER

    2006-01-01

    With the availability of better treatment and prophylactic regimens for the infectious complications of human immunod- eficiency virus (HIV), the non-infectious complications are gaining greater attention. HIV-related pulmonary arterial hypertension (HIV-PAH) is one of these. The incidence of HIV-PAH is estimated at 0.5% of HIV-infected individuals. The pathogenesis remains unclear. Patients present with symptoms as diverse as progressive shortness of

  10. Intravenous nicardipine in hypertensive children

    Microsoft Academic Search

    J. M. Treluyer; P. Hubert; P. Jouvet; S. Couderc; M. Cloup

    1993-01-01

    Fourteen hypertensive patients hospitalized in a paediatric intensive care unit were studied to evaluate safety and hypotensive efficacy of intravenous nicardipine. Systolic and diastolic blood pressure significantly decreased 1 h after the beginning of the treatment (1 ?g\\/kg per minute). Mean decrease in systolic blood pressure during the first 24 h was between 9.9% and 13.4% of the initial value.

  11. [Endothelial dysfunction and arterial hypertension].

    PubMed

    Marecková, Z; Heller, S; Horký, K

    1999-04-01

    The endothelium lines all blood vessels in the human body, it is the basic structure which ensures the action of substances circulating in the blood stream on the vascular wall. It is an organ the sound state of which is essential for the physiological function of the vascular system. Its impaired function is a basic factor in the genesis and development of vascular disease. Under physiological conditions the endothelium has antiadhesive and antithrombotic properties, it produces vasoactive substances, prevents the penetration of circulating substances and formed elements across the vascular wall, and via adhesion molecules it participates in the interaction with cells in the circulation. Risk factors of cardiovascular diseases such as hypertension, hyperlipidaemia, hyperglycaemia, smoking damage the function of endothelial cells and cause the development of endothelial dysfunction. In patients with arterial hypertension endothelial dysfunction is characterized by an impaired endothelium dependent relaxation, increased adhesion and permeability of endothelial cells, structural changes of the vascular wall. When the endothelium is damaged by released cytokines an increased expression of adhesion molecules occurs, adhesion and migration of inflammatory cells across the vascular wall. Cytoadhesion molecules are released from the surface of the endothelium into the circulation where the rise of their plasma levels can serve as a marker of endothelial damage. Endothelial dysfunction in hypertonic subjects contributes in a significant way to the development and progression of chronic vascular disease--atherosclerosis. Improvement of the damaged endothelial function is therefore at present a desirable therapeutic objective in the treatment of hypertension. PMID:11045186

  12. Secondary headaches attributed to arterial hypertension

    PubMed Central

    Assarzadegan, Farhad; Hesami, Omid; Aryani, Omid; Mansouri, Behnam; Beladi moghadam, Nahid

    2013-01-01

    Mild (140 to 159/90 to 99 mmHg) or moderate (160 to 179/100 to 109 mmHg) chronic arterial hypertension does not appear to cause headache. Whether moderate hypertension predisposes patients to headache at all remains controversial, but there is little evidence that it does. Ambulatory blood pressure monitoring in patients with mild and moderate hypertension has shown no convincing relationship between blood pressure fluctuations over a 24-hour period and presence or absence of headache. However, headaches are associated to various disorders that lead to abrupt, severe, and paroxysmal elevations in blood pressure. In this paper, the secondary headaches attributed to acute crises of hypertension and the criteria for diagnosing each of them have been reviewed. These are headaches attributed to pheochromocytoma, hypertensive crisis without encephalopathy, hypertensive encephalopathy, pre-eclampsia, eclampsia, and acute pressure response to exogenous agents. PMID:24250915

  13. Resistant Hypertension Workup and Approach to Treatment

    PubMed Central

    Makris, Anastasios; Seferou, Maria; Papadopoulos, Dimitris P.

    2011-01-01

    Resistant hypertension is defined as blood pressure above the patient's goal despite the use of 3 or more antihypertensive agents from different classes at optimal doses, one of which should ideally be a diuretic. Evaluation of patients with resistive hypertension should first confirm that they have true resistant hypertension by ruling out or correcting factors associated with pseudoresistance such as white coat hypertension, suboptimal blood pressure measurement technique, poor adherence to prescribed medication, suboptimal dosing of antihypertensive agents or inappropriate combinations, the white coat effect, and clinical inertia. Management includes lifestyle and dietary modification, elimination of medications contributing to resistance, and evaluation of potential secondary causes of hypertension. Pharmacological treatment should be tailored to the patient's profile and focus on the causative pathway of resistance. Patients with uncontrolled hypertension despite receiving an optimal therapy are candidates for newer interventional therapies such as carotid baroreceptor stimulation and renal denervation. PMID:21234416

  14. Managing Hypertension in the Newborn Infants

    PubMed Central

    Nickavar, Azar; Assadi, Farahnak

    2014-01-01

    Hypertension in newborn infants, particularly those requiring intensive care, is becoming increasingly recognized, with prevalence of 0.2-3%. Recent studies have established normative tables for blood pressure (BP) in both term and pre-term infants based on the gestational age, postnatal age, gender, weight and height, identifying the neonates at increased risk for early-onset cardiovascular disease. Common causes of neonatal hypertension include thromboembolic complications secondary to umbilical artery catheterization, congenital renal structural malformation, renovascular disease, aortic coarctation, as well as acute kidney injury and certain medications. A careful diagnostic evaluation should lead to identification of the underlying cause of hypertension in most infants. Treatment options should be tailored to the severity; and underlying cause of hypertension, including intravenous and/or oral therapy. This review summarizes recent work in these areas, focusing on optimal BP measurement, definition, evaluation and management of hypertension as well as advances in drug therapy of neonatal hypertension. PMID:24791189

  15. Hypertension in rats deficient in copper

    SciTech Connect

    Klevay, L.M.

    1986-03-01

    Male weanling rats were matched into two groups of equal mean weight (48 g), were fed a diet low in copper and zinc and were supplemented with a drinking solution with 10..mu..gZn and 2/sup +/gCu per ml until they grew to approximately 300 g. Systolic blood pressure (mmHg) was measured without anesthesia with an Electro-Sphygmomanometer and pneumatic pulse transducer; no significant difference between groups was found (0 > 0.05). Then copper was omitted from the solution of the group with lower blood pressure in each of two experiments. Plasma cholesterol (mg/dl) was measured by fluorometry and blood pressure was measured again 53 to 86 days later; mean (SE), n = 14, 15. Hypercholesterolemia verified deficiency. Hypotension in copper deficient rats in experiments of others probably was the result of cardiac defects induced in weanling animals. Hypertension joins hypercholesterolemia, hyperuricemia, glucose intolerance and abnormal electrocardiograms as a stigma of copper deficiency. Copper deficiency is the only nutritional insult that induces all of these characteristics useful in predicting risk of ischemic heart disease.

  16. Hypertension in young children and neonates

    Microsoft Academic Search

    John Edward Jones; Pedro A. Jose

    2005-01-01

    Hypertension is most often considered a disease of old age, but the precursors are often present in young children long before\\u000a the clinically accepted definitions of hypertension in the adult are manifested. Essential hypertension is by far the most\\u000a common form of the disease, comprising a complex interaction of genetic and environmental factors. Many individual genes that\\u000a play a role

  17. Sequelae of Hypertension in Children and Adolescents

    Microsoft Academic Search

    Donald J. Weaver; Mark M. Mitsnefes

    \\u000a Hypertension is a significant public health challenge because of its high prevalence as well as its associated complications\\u000a including cerebrovascular disease, renal failure, and heart failure (1). In fact, hypertension is the second leading cause of end-stage renal disease (ESRD) among adults in the USA (2). Moreover, hypertension is the leading risk factor for cardiovascular mortality and ranked third as

  18. Orthostatic hypertension: when pressor reflexes overcompensate

    Microsoft Academic Search

    Joshua Fessel; David Robertson

    2006-01-01

    Orthostatic hypertension—a rise in blood pressure upon assuming upright posture—is an underappreciated and understudied clinical phenomenon. There is currently no widely agreed-upon definition of clinical orthostatic hypertension, the current definitions being operational within the context of particular studies. The underlying pathophysiology is thought to involve activation of the sympathetic nervous system, but the actual etiology is poorly understood. Orthostatic hypertension

  19. Pathology and Management of Portopulmonary Hypertension

    Microsoft Academic Search

    Michael J. Krowka

    \\u000a Portopulmonary hypertension (POPH) is the well-recognized relationship of pulmonary artery hypertension that evolves as a\\u000a consequence of portal hypertension. POPH was first reported by Mantz and Craige in a 53-year-old female patient who presented\\u000a with sudden hoarseness due to a large spontaneous portocaval shunt (1.5–3 cm in diameter) that lay in intimate relationship\\u000a with the left recurrent laryngeal nerve as

  20. Pulmonary venous hypertension or pulmonary hypertension due to left heart disease

    Microsoft Academic Search

    Ian Adatia; Tom Kulik; Mary Mullen

    2009-01-01

    Pulmonary venous hypertension may be caused by increased pressure anywhere between the intraparenchymal pulmonary veins and the left ventricle. Pulmonary venous hypertension has different causes in children compared with adults. In adults the most common cause of pulmonary venous hypertension is left ventricular diastolic disease. In children, congenital heart diseases, acquired and congenital cardiomyopathies are the usual causes of pulmonary

  1. Mitochondrial Dysfunction in the Hypertensive Rat Brain Respiratory Complexes Exhibit Assembly Defects in Hypertension

    Microsoft Academic Search

    Ana Lopez-Campistrous; Wang Xiang; Dong Ton; Paul Semchuk; Joerg Sander; Michael J. Ellison; Carlos Fernandez-Patron

    2010-01-01

    The central nervous system plays a critical role in the normal control of arterial blood pressure and in its elevation in virtually all forms of hypertension. Mitochondrial dysfunction has been increasingly associated with the development of hypertension. Therefore, we examined whether mitochondrial dysfunction occurs in the brain in hypertension and characterized it at the molecular scale. Mitochondria from whole brain

  2. Management guidelines in essential hypertension: report of the second working party of the British Hypertension Society

    Microsoft Academic Search

    P Sever; G Beevers; C Bulpitt; A Lever; L Ramsay; J Reid; J Swales

    1993-01-01

    Several important new issues have arisen in the management of patients with hypertension. A working party of the British Hypertension Society has therefore reviewed available intervention studies on anti-hypertensive treatment and made recommendations on blood pressure thresholds for intervention, on non-pharmacological and pharmacological treatments, and on treatment goals. This report also provides guidelines on blood pressure measurement, essential investigations, referrals

  3. Physical Activity and the Prevention of Hypertension

    PubMed Central

    Diaz, Keith M.; Shimbo, Daichi

    2013-01-01

    As the worldwide prevalence of hypertension continues to increase, the primary prevention of hypertension has become an important global public health initiative. Physical activity is commonly recommended as an important lifestyle modification that may aid in the prevention of hypertension. Recent epidemiologic evidence has demonstrated a consistent, temporal, and dose-dependent relationship between physical activity and the development of hypertension. Experimental evidence from interventional studies have further confirmed a relationship between physical activity and hypertension as the favorable effects of exercise on blood pressure reduction have been well characterized in recent years. Despite the available evidence strongly supporting a role for physical activity in the prevention of hypertension, many unanswered questions regarding the protective benefits of physical activity in high-risk individuals, the factors that may moderate the relationship between physical activity and hypertension, and the optimal prescription for hypertension prevention remain. We review the most recent evidence for the role of physical activity in the prevention of hypertension and discuss recent studies that have sought to address these unanswered questions. PMID:24052212

  4. Association between Hypertension and Periodontitis: Possible Mechanisms

    PubMed Central

    Badiah, Baharin

    2014-01-01

    This review is to examine the current literatures on the relationship between periodontitis and hypertension as well as to explore the possible biological pathways underlying the linkage between these health conditions. Hypertension is one of the major risk factors for cardiovascular diseases. Oxidative stress and endothelial dysfunction are among the critical components in the development of hypertension. Inflammation has received much attention recently and may contribute to a pivotal role in hypertension. Periodontitis, a chronic low-grade inflammation of gingival tissue, has been linked to endothelial dysfunction, with blood pressure elevation and increased mortality risk in hypertensive patients. Inflammatory biomarkers are increased in hypertensive patients with periodontitis. Over the years, various researches have been performed to evaluate the involvement of periodontitis in the initiation and progression of hypertension. Many cross-sectional studies documented an association between hypertension and periodontitis. However, more well-designed prospective population trials need to be carried out to ascertain the role of periodontitis in hypertension. PMID:24526921

  5. Methylprednisolone attenuates the pulmonary hypertensive response in porcine meconium aspiration.

    PubMed

    Soukka, H; Halkola, L; Aho, H; Rautanen, M; Kero, P; Kääpä, P

    1997-08-01

    Severe neonatal aspiration of meconium is frequently complicated by fatal pulmonary hypertension. The protective effect of an i.v. bolus of methylprednisolone on meconium aspiration-induced hypertensive lung injury was studied in anesthetized pigs with adapted lung circulation. Eleven 10-wk-old pigs received 3 mL/kg 20% human meconium via the endotracheal tube. Five of them were pretreated with 30 mg/kg methylprednisolone 30 min before aspiration. Ventilator settings were adjusted to keep arterial PO2 above 8 kPa and arterial PCO2 below 5 kPa. Meconium insufflation induced a biphasic pulmonary pressor response during the 6 h follow-up. Methylprednisolone tended to prevent the early (0-1 h) increase in pulmonary artery pressure and inhibited significantly the second phase (1-6 h) progressive rise in pulmonary artery pressure and pulmonary vascular resistance. This inhibition of resistance increase was most profound in the postarterial segment of the lung circulation, as determined by pulmonary artery occlusion. Additionally, the methylprednisolone pretreated group demonstrated a significant decrease in venous admixture together with improved oxygenation during the late phase after the insult, and further showed evidence of diminished lung edema formation. Although meconium aspiration-induced fall in blood leukocyte concentration was inhibited by methylprednisolone pretreatment, no histologic difference was found in pulmonary leukocyte sequestration. Our results thus show that in adapted porcine lungs methylprednisolone pretreatment improves oxygenation and attenuates the meconium aspiration-induced pulmonary hypertensive response by preventing the increase in the postarterial resistance. PMID:9262214

  6. Leptin and regulatory T lymphocytes in idiopathic pulmonary arterial hypertension

    E-print Network

    Paris-Sud XI, Université de

    Leptin and regulatory T lymphocytes in idiopathic pulmonary arterial hypertension Alice Huertas1 pulmonary arterial hypertension (IPAH) genesis and/or progression but the pathophysiology is still unclear of IPAH. Key words: dysimmunity, endothelial dysfunction, leptin, pulmonary arterial hypertension

  7. Differential brain angiotensin-II type I receptor expression in hypertensive rats.

    PubMed

    Braga, Valdir A

    2011-09-01

    Blood-borne angiotensin-II (Ang-II) has profound effects in the brain. We tested the hypothesis that Ang-II-dependent hypertension involves differential Ang-II type I (AT(1)) receptors expression in the subfornical organ (SFO) and the rostral ventrolateral medulla (RVLM). Male Wistar rats were implanted with 14-day osmotic minipump filled with Ang-II (150 ng/kg/min) or saline. AT(1) receptor mRNA levels were detected in the SFO and RVLM by reverse transcription-polymerase chain reaction (RT-PCR). Ang-II caused hypertension (134 ± 10 mmHg vs. 98 ± 9 mmHg, n = 9, p < 0.05). RT-PCR revealed that Ang-II infusion induced increased AT(1) receptor mRNA levels in RVLM and decreased in SFO. Our data suggest that Ang-II-induced hypertension involves differential expression of brain AT(1) receptors. PMID:21897104

  8. Calcium homeostasis is altered in skeletal muscle of spontaneously hypertensive rats: cytofluorimetric and gene expression analysis.

    PubMed

    Liantonio, Antonella; Camerino, Giulia M; Scaramuzzi, Antonia; Cannone, Maria; Pierno, Sabata; De Bellis, Michela; Conte, Elena; Fraysse, Bodvael; Tricarico, Domenico; Conte Camerino, Diana

    2014-10-01

    Hypertension is often associated with skeletal muscle pathological conditions related to function and metabolism. The mechanisms underlying the development of these pathological conditions remain undefined. Because calcium homeostasis is a biomarker of muscle function, we assessed whether it is altered in hypertensive muscles. We measured resting intracellular calcium and store-operated calcium entry (SOCE) in fast- and slow-twitch muscle fibers from normotensive Wistar-Kyoto rats and spontaneously hypertensive rats (SHRs) by cytofluorimetric technique and determined the expression of SOCE gene machinery by real-time PCR. Hypertension caused a phenotype-dependent dysregulation of calcium homeostasis; the resting intracellular calcium of extensor digitorum longus and soleus muscles of SHRs were differently altered with respect to the related muscle of normotensive animals. In addition, soleus muscles of SHR showed reduced activity of the sarcoplasmic reticulum and decreased sarcolemmal calcium permeability at rest and after SOCE activation. Accordingly, we found an alteration of the expression levels of some SOCE components, such as stromal interaction molecule 1, calcium release-activated calcium modulator 1, and transient receptor potential canonical 1. The hypertension-induced alterations of calcium homeostasis in the soleus muscle of SHRs occurred with changes of some functional outcomes as excitability and resting chloride conductance. We provide suitable targets for therapeutic interventions aimed at counterbalancing muscle performance decline in hypertension, and propose the reported calcium-dependent parameters as indexes to predict how the antihypertensive drugs could influence muscle function. PMID:25084345

  9. Stimulation of angiotensin type 1A receptors on catecholaminergic cells contributes to angiotensin-dependent hypertension.

    PubMed

    Jancovski, Nikola; Bassi, Jaspreet K; Carter, David A; Choong, Yan-Ting; Connelly, Angela; Nguyen, Thu-Phuc; Chen, Daian; Lukoshkova, Elena V; Menuet, Clement; Head, Geoffrey A; Allen, Andrew M

    2013-11-01

    Hypertension contributes to multiple forms of cardiovascular disease and thus morbidity and mortality. The mechanisms inducing hypertension remain unclear although the involvement of homeostatic systems, such as the renin-angiotensin and sympathetic nervous systems, is established. A pivotal role of the angiotensin type 1 receptor in the proximal tubule of the kidney for the development of experimental hypertension is established. Yet, other systems are involved. This study tests whether the expression of angiotensin type 1A receptors in catecholaminergic cells contributes to hypertension development. Using a Cre-lox approach, we deleted the angiotensin type 1A receptor from all catecholaminergic cells. This deletion did not alter basal metabolism or blood pressure but delayed the onset of angiotensin-dependent hypertension and reduced the maximal response. Cardiac hypertrophy was also reduced. The knockout mice showed attenuated activation of the sympathetic nervous system during angiotensin II infusion as measured by spectral analysis of the blood pressure. Increased reactive oxygen species production was observed in forebrain regions, including the subfornical organ, of the knockout mouse but was markedly reduced in the rostral ventrolateral medulla. These studies demonstrate that stimulation of the angiotensin type 1A receptor on catecholaminergic cells is required for the full development of angiotensin-dependent hypertension and support an important role for the sympathetic nervous system in this model. PMID:24001896

  10. Consistent antioxidant and antihypertensive effects of oral sodium nitrite in DOCA-salt hypertension

    PubMed Central

    Amaral, Jefferson H.; Ferreira, Graziele C.; Pinheiro, Lucas C.; Montenegro, Marcelo F.; Tanus-Santos, Jose E.

    2015-01-01

    Hypertension is a common disease that includes oxidative stress as a major feature, and oxidative stress impairs physiological nitric oxide (NO) activity promoting cardiovascular pathophysiological mechanisms. While inorganic nitrite and nitrate are now recognized as relevant sources of NO after their bioactivation by enzymatic and non-enzymatic pathways, thus lowering blood pressure, mounting evidence suggests that sodium nitrite also exerts antioxidant effects. Here we show for the first time that sodium nitrite exerts consistent systemic and vascular antioxidant and antihypertensive effects in the deoxycorticosterone-salt (DOCA-salt) hypertension model. This is particularly important because increased oxidative stress plays a major role in the DOCA-salt hypertension model, which is less dependent on activation of the renin-angiotensin system than other hypertension models. Indeed, antihypertensive effects of oral nitrite were associated with increased plasma nitrite and nitrate concentrations, and completely blunted hypertension-induced increases in plasma 8-isoprostane and lipid peroxide levels, in vascular reactive oxygen species, in vascular NADPH oxidase activity, and in vascular xanthine oxidoreductase activity. Together, these findings prov