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1

Placenta in PIH.  

PubMed

A variety of changes in placental villi are known to occur in Pregnancy Induced Hypertension. In this study an attempt is made to study 49 placentae from PIH and its correlation to perinatal outcome. Quantification of villous lesions was carried out. The striking villious changes were cytotrophoblastic proliferation, paucity of vasculosyncytial membrane, trophoblastic basement membrane thickening and fibrinoid necrosis of villi. The changes were directly proportional to the severity of disease and perinatal outcome was worse with advancing grades of PIH. PMID:17883116

Kurdukar, M D; Deshpande, N M; Shete, S S; Zawar, M P

2007-07-01

2

Renin-angiotensin-aldosterone system in pregnancy-induced hypertension  

Microsoft Academic Search

Angiotensin-converting enzyme (ACE) and aldosterone concentration were measured in the plasma of 32 pregnant women with normal blood pressure or with pregnancy-induced hypertension (PIH). Mean arterial pressure (MAP) in PIH women was significantly higher than in normotensive pregnant women. Plasma ACE activity and aldosterone concentration in 17 PIH patients was significantly lower than their normotensive counterparts (15 cases). Mean arterial

A Israel; A Peceño

2000-01-01

3

Prediction of pregnancy-induced hypertension by a shift of blood pressure class according to the JSH 2009 guidelines  

Microsoft Academic Search

Elevated blood pressure (BP) at early or mid pregnancy is a known risk factor for pregnancy-induced hypertension (PIH). However, the association between BP changes during the first half of pregnancy and subsequent PIH development is unknown. We used changes in maternal BP between 16 and 20 weeks of gestation to evaluate the risk of PIH. A total of 976 pregnant

Seung Chik Jwa; Naoko Arata; Naoko Sakamoto; Noriyoshi Watanabe; Hiroaki Aoki; Asako Kurauchi-Mito; Qiu Dongmei; Yukihiro Ohya; Atsuhiro Ichihara; Michihiro Kitagawa

2011-01-01

4

Duplex Doppler ultrasound in the evaluation of pregnancies complicated by pregnancy-induced hypertension.  

PubMed

Umbilical artery velocimetry using pulsed Doppler technique was carried out in 49 pregnancies complicated by pregnancy-induced hypertension (PIH). Outcome of the pregnancies was evaluated after delivery. We found the systolic to diastolic ratio of the umbilical artery to be highly sensitive and specific in predicting abnormal outcome in pregnancies complicated by PIH. In our opinion, the pulsed Doppler technique can be a useful adjunct to other methods for evaluation of fetal well-being in patients with PIH. PMID:1763617

Ben-Ami, M; Battino, S; Weiner, E; Shalev, E

1991-01-01

5

The efficacy of biobehavioral and compliance interventions in the adjunctive treatment of mild pregnancy-induced hypertension  

Microsoft Academic Search

This investigation assessed the efficacy of a biobehavioral intervention in the adjunctive treatment of mild pregnancy-induced hypertension (PIH), a potentially serious complication of pregnancy in which normotensive women develop hypertension, proteinuria, and edema of unknown etiology late in gestation. Forty-five women with symptoms of PIH were randomly assigned to one of three treatment conditions: bed rest alone (the most common

Peter J. Somers; Richard N. Gevirtz; Susan E. Jasin; Homer G. Chin

1989-01-01

6

Predicting pregnancy-induced hypertension with dynamic hemodynamics  

Microsoft Academic Search

Aim: To study dynamic changes in the hemodynamic parameters in pregnant women during different weeks of gestation and to comprehend changes to the cardiovascular system in normal pregnant women and in patients with pregnancy-induced hypertension (PIH), with the object of finding predictors of pregnancy-induced hypertension. Methods: Radialis artery pulse waves of 132 pregnant women were examined from 10 weeks of

Juan Song; Song Zhang; Ye Qiao; Zhicang Luo; Jianhua Zhang; Yanjun Zeng; Lijuan Wang

2004-01-01

7

Labetalol vs. methyldopa in the treatment of pregnancy-induced hypertension  

Microsoft Academic Search

Objective: To assess the efficacy and safety of labetalol compared with methyldopa in the management of mild and moderate cases of pregnancy-induced hypertension (PIH). Methods: One hundred four primigravidas with PIH were randomly allocated to receive either labetalol (group A) or methyldopa (group B). The dose of the drugs was doubled every 48 h to maintain a mean arterial blood

A. M. El-Qarmalawi; A. H. Morsy; A. Al-Fadly; A. Obeid; M. Hashem

1995-01-01

8

Co-relation of Pregnancy induced Hypertension with Placental Abruption and Effect of Antihypertensive Therapy  

Microsoft Academic Search

Objective: To co-rrelate clinically Pregnancy Induced Hypertension (PIH) with abruption and to see the effect of antihypertensive therapy. Methods: Fifty pregnant women with PIH and 50 normotensive pregnant women with singleton pregnancy at gestational age more than 20 weeks were studied. Clinical evaluation consisted of a comprehensive history and antenatal record. All deliveries were planned in Holy Family Hospital (HFH).

Huma Tasleem; Samina Tasleem; Malik Muhammad Adil; Khalida Waheed

9

Pregnancy-induced hypertension and reduced intraventricular hemorrhage in preterm infants  

Microsoft Academic Search

Increasing evidence suggests that the incidence of periventricular intraventricular hemorrhage (PV-IVH) is lower in infants born to mothers with pregnancy-induced hypertension (PIH). The mechanism or mechanisms accounting for this reduction remain unclear but may be related to PIH itself, medications used to treat the mother (e.g., magnesium sulfate), or to obstetrical management. In this retrospective analysis, we determined the incidence

Jeffrey M. Perlman; Richard C. Risser; Jerry B. Gee

1997-01-01

10

Nifedipine attenuates the hypertensive response to tracheal intubation in pregnancy-induced hypertension  

Microsoft Academic Search

Thirty women with pregnancy-induced hypertension (PIH) scheduled for Caesarean section under general anaesthesia were studied\\u000a to evaluate the efficacy of sublingual nifedipine in attenuating the pressor response to laryngoscopy and tracheal intubation.\\u000a The patients were randomly given either the contents of a nifedipine capsule 10 mg or placebo sublingually 20 min before induction\\u000a of anaesthesia. Blood pressure and heart rate

Nanda Kumar; Y. K. Batra; Indu Bala; S. Gopalan

1993-01-01

11

Granulocyte colony-stimulating factor in the cord blood of premature neonates born to mothers with pregnancy-induced hypertension  

Microsoft Academic Search

Objectives: To estimate the cord blood levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in preterm infants and to study the relationship of these levels to pregnancy-induced hypertension (PIH) and absolute neutrophil counts. Study design: G-CSF and GM-CSF levels in the cord blood of preterm neonates (n = 74) either with or without maternal PIH were estimated

Po-Nien Tsao; Ru-Jeng Teng; Jen-Ruey Tang; Kuo-Inn Tsou Yau

1999-01-01

12

Prediction of pregnancy-induced hypertension by a shift of blood pressure class according to the JSH 2009 guidelines.  

PubMed

Elevated blood pressure (BP) at early or mid pregnancy is a known risk factor for pregnancy-induced hypertension (PIH). However, the association between BP changes during the first half of pregnancy and subsequent PIH development is unknown. We used changes in maternal BP between 16 and 20 weeks of gestation to evaluate the risk of PIH. A total of 976 pregnant women with BP estimations recorded before 16 weeks and at 20 weeks of gestation participated in this study. BPs were classified by the Japanese Society of Hypertension 2009 Hypertension Treatment Guidelines (JSH 2009). There was a significant trend for future PIH in women whose JSH 2009 BP class increased between 16 and 20 weeks of gestation, and the risk of PIH was highest among women whose BP was Class IV Hypertension (systolic BP?140?mm?Hg and/or diastolic BP?90?mm?Hg). The risk of PIH increased in women whose BPs shifted from Classes I Optimal (systolic BP<120?mm?Hg and diastolic BP<80?mm?Hg) and II Normal (systolic BP 120-129?mm?Hg and/or diastolic BP 80-84?mm?Hg) before 16 weeks to Class III High-Normal (systolic BP 130-139?mm?Hg and/or diastolic BP 85-89?mm?Hg) at 20 weeks of gestation. These shifts in BP class were significantly correlated with the risk of PIH after adjustments for variables (P-value for trend <0.05). Within JSH 2009 Classes I, II and III, a shift in BP from a low to a high class between 16 and 20 weeks of gestation predicts the subsequent development of PIH. PMID:21796130

Jwa, Seung Chik; Arata, Naoko; Sakamoto, Naoko; Watanabe, Noriyoshi; Aoki, Hiroaki; Kurauchi-Mito, Asako; Dongmei, Qiu; Ohya, Yukihiro; Ichihara, Atsuhiro; Kitagawa, Michihiro

2011-07-28

13

Lower segment cesarean section in a patient with severe thrombocytopenia and pregnancy induced hypertension  

PubMed Central

Thrombocytopenia in pregnancy carries a major risk of feto-maternal morbidity and mortality. We present a case of hypocellular bone marrow with severe thrombocytopenia with pregnancy induced hypertension (PIH) for emergency lower segment cesarean section (LSCS). This disease is characterized by pancytopenia and hypocellular bone marrow with impaired morphology and maturation. Causes of death due to this disease include hemorrhage and infection secondary to thrombocytopenia and neutropenia especially following surgery. We report successful management of emergency LSCS with severe thrombocytopenia with severe PIH.

Harde, Minal; Dave, Sona; Vasave, Rahul Ramji; Gujjar, Pinakin; Bhadade, Rakesh

2013-01-01

14

The effect of isosorbide dinitrate on placental blood flow and maternal blood pressure in women with pregnancy induced hypertension  

Microsoft Academic Search

The effect of isosorbide dinitrate (ISDN) on maternal and fetal circulation was assessed in 23 women with pregnancy induced hypertension (PIH). A double-blind randomized design was employed. Each woman was given a sublingual tablet of ISDN (5 mg) or placebo. Maternal blood pressure (BP) and heart rate (HR) were measured before and every 2 min after the medication or placebo,

Israel Thaler; Amnon Amit; Daniel Kamil; Joseph Itskovitz-Eldor

1999-01-01

15

Effect of early postnatal neutropenia in very low birth weight infants born to mothers with pregnancy-induced hypertension  

PubMed Central

Purpose In this study, we aimed to investigate the perinatal clinical conditions of very low birth weight (VLBW) infants born to mothers with pregnancy-induced hypertension (PIH) focusing on the effects of early postnatal neutropenia. Methods We reviewed the medical records of 191 VLBW infants who were born at Konyang University Hospital, between March 2003 and May 2011. We retrospectively analyzed the clinical characteristics of the infants and their mothers and compared the incidence of perinatal diseases and mortality of the infants according to the presence or absence of maternal PIH and neutropenia on the first postnatal day. Results Infants born to mothers with PIH showed an increased incidence of neutropenia on the first postnatal day (47.4%), cesarean delivery, and intrauterine growth restriction. When the infants born to mothers with PIH showed neutropenia on the first postnatal day, their incidence of respiratory distress syndrome (RDS) was increased (P=0.031); however, the difference was not found to be significant through logistic regression analysis. In all the VLBW infants, neutropenia on the first postnatal day was correlated with the development of RDS. The incidence of the other perinatal diseases involving sepsis and mortality did not significantly differ according to the presence or absence of neutropenia in infants born to mothers with PIH. Conclusion In VLBW infants born to mothers with PIH, the incidence of neutropenia on the first postnatal day was increased and it was not significantly correlated with the development of perinatal diseases involving RDS, sepsis, and mortality.

Park, Yang Hee; Lee, Gyung Min; Yoon, Jung Min; Cheon, Enn Jung; Ko, Kyung Ok; Lee, Yung Hyuk

2012-01-01

16

LEPR c.668A>G polymorphism in a cohort of Sri Lankan women with pre-eclampsia / pregnancy induced hypertension: a case control study  

PubMed Central

Background Leptin is known to be elevated in pre-eclampsia/ pregnancy induced hypertension (PE/PIH). However the reports on the association of leptin receptor (LEPR) c.668A>G polymorphism with PE/PIH are inconsistent. Findings LEPR c.668A>G polymorphism was studied in a cohort of women with PE/PIH (N?=?61) and normotensive pregnancies (N?=?40) by polymerase chain reaction / restriction fragment length polymorphism. Genotype and allele frequencies were in Hardy-Weinberg equilibrium within both groups (Chi square test). Allele and genotype frequencies were not significantly different between PE/PIH and normotensive pregnancies (Chi square test). Leptin levels (Kruskal Wallis analysis of variance) and leptin/body mass index (one way analysis of variance) were not significantly different between genotypes within each group. However, leptin (Mann Whitney U test) and leptin normalised to body mass index (unpaired t test) were significantly higher in PE/PIH women homozygous and heterozygous for the G668 allele than in respective normotensives. Conclusions Whether the leptin receptor c.668A>G polymorphism increases the risk of developing PE/PIH in Sri Lankan women remains inconclusive in view of the smaller sample studied. However leptin levels in PE/PIH appeared to be modulated by this polymorphism.

2012-01-01

17

The relationship between preeclampsia, pregnancy-induced hypertension and maternal risk of breast cancer: A meta-analysis.  

PubMed

Abstract Background. It has long been recognized that some human breast cancers are hormone dependent. Preeclampsia is a syndrome of pregnancy defined by the onset of hypertension and proteinuria and characterized by dysfunction of the maternal endothelium. Many hormonal changes occur with preeclampsia, and we hypothesize that these changes may influence the risk of maternal breast cancer. We also analyzed the relation between pregnancy-induced hypertension (PIH) and maternal risk of breast cancer. Methods. Among 13 relevant publications about preeclampsia and six relevant publications about PIH, some studies find preeclampsia associated with a lower risk of breast cancer, but others did not. Therefore, these results are inconclusive. We conducted meta-analysis to evaluate more precisely the relationship between preeclampsia, PIH and maternal risk of breast cancer. Results. The pooled estimate of the hazard ratio (HR) associated with preeclampsia was 0.86 (95% CI 0.73-1.01), and that associated with PIH was 0.83 (0.66-1.06), both based on the random effects model. Conclusion. Some suggestive but not entirely consistent nor conclusive evidence was found on the association between the history of preeclampsia or PIH with the subsequent risk of breast cancer. PMID:23240638

Kim, Jung Sun; Kang, Eun Joo; Woo, Ok Hee; Park, Kyong Hwa; Woo, Sang Uk; Yang, Dae Sik; Kim, Ae-Ree; Lee, Jae-Bok; Kim, Yeul Hong; Kim, Jun Suk; Seo, Jae Hong

2012-12-16

18

Angiotensin Type 1 Receptor Blockade Prevents Cardiac Remodeling in Mice with Pregnancy-Associated Hypertension  

Microsoft Academic Search

Pregnancy-induced hypertension (PIH) is a life-threatening disorder for both mother and fetus; cardiac dysfunction is the major complication and can result in further deterioration. Recently, it has been recognized that aberrant activation of angiotensin type 1 receptor (AT1) signaling contributes to the pathogenesis of PIH, but the details of the relationship between cardiac injury and enhanced AT1 signaling in PIH

Akira Sakairi; Junji Ishida; Kaori Honjo; Saki Inaba; Shoko Nakamura; Fumihiro Sugiyama; Ken-Ichi Yagami; Akiyoshi Fukamizu

2008-01-01

19

Effect of Methyldopa on Renal Function in Rats with L-NAME-Induced Hypertension in Pregnancy  

Microsoft Academic Search

Background: Pregnancy-induced hypertension is characterized by an increased sympathetic activity and probably by a decreased synthesis\\/activity of nitric oxide. The aim of the present study is to evaluate whether the beneficial action of the sympathetic antagonist methyldopa (a first-choice hypotensive agent in the treatment of PIH) may be associated to changes in nitric-oxide synthesis. Methods: Forty pregnant Wistar rats received

Eduardo Podjarny; Sydney Benchetrit; Bernard Katz; Janice Green; Jacques Bernheim

2001-01-01

20

Effect of prepared rhubarb on insulin resistance in patients with pregnancy induced hypertension  

Microsoft Academic Search

Objective:To investigate the effect of prepared rhubarb on insulin resistance in patients with pregnancy induced hypertension (PIH)\\u000a and its mechanism.Methods: All the 92 patients accepted 75 g oral glucose tolerance test (OGTT) and insulin release test before and after treatment.\\u000a These patients were divided into two groups (treated group and control group). Prepared rhubarb and nifedipine were given\\u000a to the

Wang Zi-fen; Shi Shao-lan; Song Hai-xiang

2003-01-01

21

Hypertensive Disorders of Pregnancy  

PubMed Central

Hypertension is the most common medical problem encountered during pregnancy, complicating 2-3% of pregnancies. Hypertensive disorders during pregnancy are classified into 4 categories, as recommended by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy: 1) chronic hypertension, 2) preeclampsia-eclampsia, 3) preeclampsia superimposed on chronic hypertension, and 4) gestational hypertension (transient hypertension of pregnancy or chronic hypertension identified in the latter half of pregnancy) (1). This terminology is preferred over the older but widely used term pregnancy-induced hypertension (PIH) because it is more precise.

Mammaro, Alessia; Carrara, Sabina; Cavaliere, Alessandro; Ermito, Santina; Dinatale, Angela; Pappalardo, Elisa Maria; Militello, Mariapia; Pedata, Rosa

2009-01-01

22

ADRB1 as a potential target for gene therapy of pregnancy induced hypertension and gestational diabetes mellitus.  

PubMed

Pregnancy-induced hypertension (PIH) and gestational diabetes mellitus (GDM) do not cause any problems with recognition; however, their pathophysiologies are still not explained. Yet many authors suggest that adrenergic ?-1 receptor (ADRB1) plays a crucial role. The aim of this study was to evaluate the transcription activity of ADRB1 by using real-time polymerase chain reaction (PCR) in placenta from normal pregnancies and from PIH and GDM. Obtained findings demonstrated a significant increase in ADRB1 mRNA expression in the examined groups in comparison to the control (p = 0.03). Our data indicate a potential perspective of ADRB1 suppression gene therapy in the treatment of PIH and GDM. PMID:21806475

Wieclawek, Agnieszka; Slawska, Helena; Mazurek, Urszula

2011-08-01

23

[Case of postpartum intracerebral hemorrhage due to pregnancy induced hypertension].  

PubMed

A 32-year-old woman, gravida 0, para 0, was admitted to the obstetrics department of our hospital after a cesarean section at 35 weeks of gestation. The cesarean section was performed because pregnancy induced hypertension (PIH) had worsened. The next day, she suddenly became drowsy and developed right hemiparesis and anisocoria. Computed tomography of the brain showed intracerebral hemorrhage in the parietal lobe with uncal herniation. She underwent an urgent craniotomy and removal of the hematoma. Five days later, magnetic resonance angiography (MRA) of the brain showed vasospasm of the bilateral intracranial internal carotid arteries, middle cerebral arteries, and anterior cerebral arteries. Thirteen days later, cerebral angiography showed cessation of vasospasm and vascular abnormalities such as moyamoya disease, arteriovenous malformation and cerebral aneurysm were not observed. Twenty-one days later, MRA showed the absence of vasospasm in those arteries, but her right hemiparesis and sensory aphasia persisted. Twenty-six days later, she was transferred to another hospital for further rehabilitation. Neurosurgeons should be aware of the possibility of intracerebral hemorrhage caused by PIH. In this manuscript, we provide a case presentation and review of the literature. PMID:22128271

Matsuda, Ryosuke; Fujimoto, Takatoshi; Tamura, Kentaro; Motoyama, Yasushi; Park, Young-Su; Nakase, Hiroyuki

2011-12-01

24

Platelet Angiotensin II Receptor Status during Pregnancy in Chinese Women at High Risk of Developing Pregnancy-Induced Hypertension  

Microsoft Academic Search

Objectives: The aims of this prospective study were to explore the changes in platelet angiotensin II (A-II) binding in pregnancy amongst Chinese women at high risk of developing pregnancy-induced hypertension (PIH) and the effects of low-dose aspirin and calcium supplementation on A-II binding. Methods: Platelet A-II binding was assayed in 15 non-pregnant women and in 63 pregnant women determined to

Michael S. Rogers; Cathy Hung; Mano Arumanayagam

1996-01-01

25

Spectrum of hypertensive emergencies in pregnancy.  

PubMed

Hypertension in pregnancy represents a spectrum of clinical entities, including pregnancy-induced hypertension (PIH), preeclampsia, eclampsia, and hemolysis, elevated liver enzyme levels, low platelet count syndrome. Although hypertension is a common denominator in this group of disorders, the pathogenesis, clinical features, and clinical course of these disorders is variable and somewhat distinct. Therapy must be tailored to the clinical entity and the patient. The incidence and prevalence of preeclampsia and eclampsia is decreasing worldwide. This decrease partly may be caused by the improved treatment of PIH and improved obstetrical services. PMID:15388197

Henry, Charles S; Biedermann, Scott A; Campbell, Michel F; Guntupalli, Jayarama S

2004-10-01

26

Maternal and Fetal Variants in the TGF-beta3 Gene and Risk of Pregnancy-Induced Hypertension in a Predominantly Latino Population  

PubMed Central

Objective To determine if polymorphisms in the Transforming Growth Factor Beta-3 (TGF-?3) gene are associated with risk of pregnancy-induced hypertension (PIH) in case-control mother-baby dyads. Study Design Cases (N=136) and controls (N=169) were recruited from the Los Angeles County + University of Southern California Women's and Children's Hospital. We genotyped four TGF-?3 polymorphisms and examined association with PIH using logistic regression, adjusting for parity, maternal age, gestational age at delivery, fetal (or maternal) genotypes for the polymorphism in question, and for the three other polymorphisms within the TGF-?3 gene. Results Only one of the TGF-?3 polymorphisms (rs11466414) was associated with PIH. Mothers who carried a baby with a minor allele were at decreased risk (ORmulti-locus adj= 0.32, 95% CI: 0.14, 0.77). Maternal TGF-?3 variants had no effect on risk of PIH. Conclusion A fetal TGF-beta3 polymorphism (rs11466414) is associated with pregnancy-induced hypertension in a predominantly Hispanic population.

WILSON, Melissa L.; DESMOND, Daniel H.; GOODWIN, T. Murphy; MILLER, David A.; INGLES, Sue Ann

2009-01-01

27

Abundant expression of platelet-derived growth factor in spiral arteries in decidua associated with pregnancy-induced hypertension and its relevance to atherosis  

Microsoft Academic Search

Objective: To elucidate the role of platelet-derived growth factor (PDGF) in the pathophysiology of pregnancy-induced hypertension (PIH) in which the spiral arteries of the decidua demonstrate the atherosclerotic change. Design and Methods: We determined serum levels of PDGF and PDGF expression in the decidua as well as serum levels of 17b-estradiol (E2) and progesterone (P4) both in normotensive cases and

Hiroki Morita; Masakazu Mizutori; Kyousuke Takeuchi; Satoru Motoyama; Takeshi Maruo

2001-01-01

28

Pre-eclampsia and pregnancy-induced hypertension are associated with severe diabetic retinopathy in type 1 diabetes later in life.  

PubMed

To investigate whether pre-eclampsia (PE) or pregnancy-induced hypertension (PIH) predicts the development of severe diabetic retinopathy (SDR) in type 1 diabetes. Altogether, 203 women with type 1 diabetes who were followed during pregnancy were re-examined within the Finnish Diabetic Nephropathy Study. After excluding patients with pre-pregnancy hypertension and those who had had laser treatment or whose retinopathy was graded as proliferative at the index pregnancy, 158 were prospectively studied. As a surrogate marker for SDR, retinal laser photocoagulation was used. The time from pregnancy to SDR (N = 21) or follow-up was 16 years (interquartile range, 11-19). HbA1c was repeatedly measured both during pregnancy and follow-up. Women with prior PE (26 % vs. 6 %, P = 0.003) or PIH (24 % vs. 6 %, P = 0.008) had more often incident SDR during follow-up compared to those with normotensive pregnancy. The hazard ratios (HR) remained associated with the progression to SDR after adjustment for duration of diabetes and diabetic nephropathy in a Cox regression analysis [PE: 3.5 (95 % CI 1.1-10.9); P = 0.03 and for PIH: 3.2 (1.1-9.8); P = 0.04]. The association between PIH and incident SDR did not change after inclusion of mean HbA1c, measured during pregnancy (all 3 trimesters) and serial HbA1c measurements during follow-up, 3.5 (1.1-11.8; P = 0.03). However, in a similar model, the HR for PE was no more significant 2.0 (0.6-6.8; P = NS). The results suggest that women with type 1 diabetes and a hypertensive pregnancy have an increased risk of severe diabetic retinopathy later in life. PMID:22955518

Gordin, Daniel; Kaaja, Risto; Forsblom, Carol; Hiilesmaa, Vilho; Teramo, Kari; Groop, Per-Henrik

2012-09-07

29

[Etiological studies of secondary hypertension. e. Drug-induced hypertension].  

PubMed

The findings of etiological studies show a relationship between secondary hypertension and various chemical agents. The subject populations included males, females, infants, adults (including people of advanced age), and healthy and unhealthy individuals, e.g., those with allergies or liver or digestive deficiencies. Results are presented in a table which shows that effects of drug-induced hypertension include expansion of extracellular fluid volume induced by sodium, antacids, and glycyrrhiza; disturbances of the autonomic nervous system caused by direct or indirect sympathomimetics;mixed or unknown mechanisms caused by poisons and various diagnostic and therapeutic agents, paradoxical response to antihypertensive agents caused by labetalol and saralasin acetate; and rebound hypertension induced by clonidine hydrochloride and methyldopa. Other drugs or chemical agents whose effects were examined include: glycyrrhizic acid, jintan, sulindac, thiazide, indo-methacin, and oral contraceptives. Based on these findings, drug-induced hypertension is observed quite frequently, a fact that has been the basis of considerable study. However, some cases indicate that even when hypertension is observed at experimental stages, insignificant hypertension is found at the clinical stage because of such factors a drug metabolism and patient sensitivity. PMID:6716694

Kato, E

1984-02-01

30

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

PubMed

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

Grossman, Ehud; Messerli, Franz H

2012-01-01

31

Pregnancy Induced Hypertension in Twin Pregnancy  

Microsoft Academic Search

Results: Pregnancy induced hypertension was found to at develop 18.36% in the twin gestations, compared with 5.03% in the singleton gestations (P<0.05). Women with twin gestations had higher rates of pregnancy induced hypertension (RR 3.65, 95% CI 2.11-6.30, P<0.05) and occurred earlier than singleton gestations (35.86±2.50 VS 37.40±1.18 weeks, P<0.05). Twin gestations with preganancy induced hypertension had significantly higher rate

Apichart Chittacharoen; Somsak Suthutvoravut

32

Drugs induced pulmonary arterial hypertension.  

PubMed

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

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

2013-08-22

33

Quantitative peptidomic analysis by a newly developed one-step direct transfer technology without depletion of major blood proteins: its potential utility for monitoring of pathophysiological status in pregnancy-induced hypertension.  

PubMed

We have recently developed a new target plate (BLOTCHIP®) for MALDI-MS. An advantage of this procedure is that it does not require the lowering of protein concentrations in test samples prior to analysis. Accordingly, this new technology enables the detection of peptides present in blood samples, including those that would otherwise be adsorbed to abundant blood proteins and would thus escape detection. Using this technology, we analyzed the peripheral blood of patients with pregnancy-induced hypertension (PIH; the most common serious complication of pregnancy) to test a potential utility of the technology for monitoring of the pathophysiological status. In the present study, we found 23 characteristic peptides for PIH in the blood serum of pregnant women. Offline LC-MALDI MS/MS identified 7 of the 23 peptides as fragments derived from kininogen-1 (three peptides), fibrinogen-?, complement component C4-A/B, ?-2-HS-glycoprotein and inter-?-trypsin inhibitor heavy chain H4. 2-D scatter plots with combinations of the peptides found in the present study can be grouped for pregnant women with/without PIH, which would be satisfactory reflected for their status. Additionally, the levels of most of these peptides found were significantly decreased by albumin/IgG depletion prior to BLOTCHIP® analysis in accordance with conventional proteomics procedures. These results indicated that BLOTCHIP® analysis can be applied for discovery study of PIH biomarker candidates. PMID:21630454

Araki, Yoshihiko; Nonaka, Daisuke; Tajima, Atsushi; Maruyama, Mayuko; Nitto, Takeaki; Ishikawa, Hitoshi; Yoshitake, Hiroshi; Yoshida, Emiko; Kuronaka, Noriko; Asada, Kyoichi; Yanagida, Mitsuaki; Nojima, Michio; Yoshida, Koyo; Takamori, Kenji; Hashiguchi, Teruto; Maruyama, Ikuro; Lee, Lyang-Ja; Tanaka, Kenji

2011-05-31

34

Stroke- and pregnancy-induced hypertensive syndromes.  

PubMed

Pregnancy-induced hypertensive syndromes are an important cause of cerebrovascular diseases during pregnancy. Women with pregnancy-induced hypertensive syndromes are at an increased risk of ischemic and hemorrhagic strokes. Posterior reversible encephalopathy and reversible vasoconstriction syndromes are common. Cerebral venous sinus thrombosis may also occur. Preeclampsia and eclampsia reflect generalized endothelial dysfunction. Prompt diagnosis and identification of patients at risk allows for early therapeutic interventions and improved clinical outcomes. PMID:21612350

Morales-Vidal, Sarkis; Schneck, Michael J; Flaster, Murray S; Biller, José

2011-05-01

35

The role of thromboxane in cuprophan–induced pulmonary hypertension  

Microsoft Academic Search

The role of thromboxane in cuprophan–induced pulmonary hypertension. Previous studies demonstrated that acute infusion of cuprophan activated plasma into experimental animals produce cardiopulmonary changes which included severe pulmonary hypertension. It was further suggested that these changes were mediated by complement activation products. The current study examined the role of arachidonic acid metabolites in the pathogenesis of cuprophan–induced pulmonary hypertension in

Alfred K Cheung; Robert L Baranowski; Andrea L Wayman

1987-01-01

36

[Case of emergent caesarean delivery in a patient with aplastic anemia complicated with pregnant induced hypertension].  

PubMed

A 32-year-old pregnant woman diagnosed with aplastic anemia was admitted for emergent caesarean delivery of 26th week of the gestation due to PIH (pregnancy-induced hypertension) and NRFS (non-reassuring fetal status). After compensating platelets counts to 5.3x10(4) microl-1, general anesthesia was induced with propofol and rocuronium. Anesthesia was maintained with O2 and sevoflurane until delivery and with modified-NLA after delivery. She was additionally monitored with Vigileo/FloTrac system (Edwards Lifesciences, USA) and TOF-WATCH SX (Nihon Kohden, Tokyo). After 8 minutes of operation her baby was born with the 5-minute Apgar score of 5 and the UA-pH of 7.387. It was only 2 hours and 12 minutes that the baby was born after she was admitted. The baby was tracheally intubated and transferred to NICU. Blood loss during operation was 835 g and two units of RCC was transfused. Circulatory values were kept acceptable and neuromuscular blocking was completely reversed by sugammadex and extubated in the operating room. Bleeding tendency and atonic bleeding were not observed. She survived perioperative period and was to be treated for aplastic anemia. Her baby was discharged neurologically free. We should be ready to respond to anesthetic requirement for urgent cases of aplastic anemia. PMID:22256582

Sakurai, Yasuyoshi; Uchida, Michiko; Aiba, Junko; Mimura, Fumiaki; Yamaguchi, Midori

2011-12-01

37

The iron chelator pyridoxal isonicotinoyl hydrazone (PIH) and its analogues prevent damage to 2-deoxyribose mediated by ferric iron plus ascorbate.  

PubMed

Iron chelating agents are essential for treating iron overload in diseases such as beta-thalassemia and are potentially useful for therapy in non-iron overload conditions, including free radical mediated tissue injury. Deferoxamine (DFO), the only drug available for iron chelation therapy, has a number of disadvantages (e.g., lack of intestinal absorption and high cost). The tridentate chelator pyridoxal isonicotinoyl hydrazone (PIH) has high iron chelation efficacy in vitro and in vivo with high selectivity and affinity for iron. It is relatively non-toxic, economical to synthesize and orally effective. We previously demonstrated that submillimolar levels of PIH and some of its analogues inhibit lipid peroxidation, ascorbate oxidation, 2-deoxyribose degradation, plasmid DNA strand breaks and 5,5-dimethylpyrroline-N-oxide (DMPO) hydroxylation mediated by either Fe(II) plus H(2)O(2) or Fe(III)-EDTA plus ascorbate. To further characterize the mechanism of PIH action, we studied the effects of PIH and some of its analogues on the degradation of 2-deoxyribose induced by Fe(III)-EDTA plus ascorbate. Compared with hydroxyl radical scavengers (DMSO, salicylate and mannitol), PIH was about two orders of magnitude more active in protecting 2-deoxyribose from degradation, which was comparable with some of its analogues and DFO. Competition experiments using two different concentrations of 2-deoxyribose (15 vs. 1.5 mM) revealed that hydroxyl radical scavengers (at 20 or 60 mM) were significantly less effective in preventing degradation of 2-deoxyribose at 15 mM than 2-deoxyribose at 1.5 mM. In contrast, 400 microM PIH was equally effective in preventing degradation of both 15 mM and 1.5 mM 2-deoxyribose. At a fixed Fe(III) concentration, increasing the concentration of ligands (either EDTA or NTA) caused a significant reduction in the protective effect of PIH towards 2-deoxyribose degradation. We also observed that PIH and DFO prevent 2-deoxyribose degradation induced by hypoxanthine, xanthine oxidase and Fe(III)-EDTA. The efficacy of PIH or DFO was inversely related to the EDTA concentration. Taken together, these results indicate that PIH (and its analogues) works by a mechanism different than the hydroxyl radical scavengers. It is likely that PIH removes Fe(III) from the chelates (either Fe(III)-EDTA or Fe(III)-NTA) and forms a Fe(III)-PIH(2) complex that does not catalyze oxyradical formation. PMID:11042379

Hermes-Lima, M; Ponka, P; Schulman, H M

2000-10-18

38

Pregnancy-induced hypertension and congenital adrenal hypoplasia.  

PubMed

Adrenal weights and histologic features in an autopsy population of 759 fetuses and neonates were correlated with the presence or absence of pregnancy-induced hypertension. Hypoplastic fetal adrenals with normal proportions of fetal and adult cortical layers (miniature histologic type) had combined adrenal weights less than 1 g, and were noted in 11 fetuses and neonates born to 39 mothers with pregnancy-induced hypertension, two born to 35 mothers with suggested pregnancy-induced hypertension, and 45 born to 685 mothers with no pregnancy-induced hypertension. Hypoplastic fetal adrenals were associated significantly with pregnancy-induced hypertension by chi 2 analysis (P less than .01). When a more stringent criterion for fetal adrenal hypoplasia was used (combined adrenal weight/body weight ratio of less than 1:1000), five cases were associated with pregnancy-induced hypertension, three with suggested pregnancy-induced hypertension, and seven with normal maternal blood pressures (P less than .001). This study confirms the relationship between pregnancy-induced hypertension and reduced fetal adrenal mass. We speculate that reduced production of dehydroepiandrosterone sulfate by the small adrenals may be related to maternal hypertension. PMID:3393361

Brown, W; Singer, D B

1988-08-01

39

Sildenafil attenuates placental ischemia-induced hypertension.  

PubMed

Preeclampsia is a complication of pregnancy that is marked by hypertension, proteinuria, and maternal endothelial dysfunction. A central factor in the etiology of the disease is the development of placental hypoxia/ischemia, which releases pathogenic soluble factors. There is currently no effective treatment for preeclampsia, but the phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been suggested, as PDE-5 is enriched in the uterus, and its antagonism could improve uteroplacental function. Here, we report in the reduced uterine perfusion pressure (RUPP) rat model that administration of oral sildenafil is effective in attenuating placental ischemia-induced hypertension during gestation. RUPP animals have significantly elevated arterial pressure compared with control animals (132 ± 3 vs. 100 ± 2 mmHg; P < 0.05). Administration of oral sildenafil (45 mg·kg(-1)·day(-1)) had no effect on blood pressure in control rats but decreased pressure in RUPP rats (115 ± 1 mmHg; P < 0.05). RUPP induced changes in placental sFlt-1, and vascular endothelial growth factor (VEGF) was unaffected by sildenafil administration, as was the decrease in free plasma VEGF. RUPP animals had a significant increase in medullary PDE-5/?-actin ratio (1 ± 0.14 vs. 1.63 ± 0.18; P < 0.05) expression with a resulting reduction in renal medullary cGMP (1.5 ± 0.15 vs. 0.99 ± 0.1 pmol/?g protein, P < 0.05) compared with controls. Although sildenafil had no effect on renal medullary cGMP in control animals, it significantly increased cGMP in RUPP animals (1.3 ± 0.1 pmol/?g protein; P < 0.05). These data suggest that sildenafil might provide an effective therapeutic option for the management of hypertension during preeclampsia. PMID:23785075

George, Eric M; Palei, Ana C; Dent, Edward A; Granger, Joey P

2013-06-19

40

49 CFR 236.1020 - Exclusion of track segments for implementation due to cessation of PIH materials service or...  

Code of Federal Regulations, 2010 CFR

...segments for implementation due to cessation of PIH materials service or rerouting. 236...segments for implementation due to cessation of PIH materials service or rerouting. (a...subject track segment. (b) Cessation of PIH materials service. Except as...

2010-10-01

41

Intestinal permeability in rats with CCl4-induced portal hypertension  

Microsoft Academic Search

AIM: To investigate the intestinal barrier changes in rats with CCl4-induced portal hypertension. METHODS: The permeability of intestinal barrier detected by Lanthanum as a tracer was evaluated in rats. Bacterial translocation and plasma endotoxin were also determined. RESULTS: The incidence of bacterial translocation was 85% in rats with CCl4-induced portal hypertension, which was signifi cantly higher than that in control

Guo-Xiang Yao; Zhong-Yi Shen; Xin-Bo Xue; Zhen Yang

42

Mechanisms of intermittent hypoxia induced hypertension.  

PubMed

Exposing rodents to brief episodes of hypoxia mimics the hypoxemia and the cardiovascular and metabolic effects observed in patients with obstructive sleep apnoea (OSA), a condition that affects between 5% and 20% of the population. Apart from daytime sleepiness, OSA is associated with a high incidence of systemic and pulmonary hypertension, peripheral vascular disease, stroke and sudden cardiac death. The development of animal models to study sleep apnoea has provided convincing evidence that recurrent exposure to intermittent hypoxia (IH) has significant vascular and haemodynamic impact that explain much of the cardiovascular morbidity and mortality observed in patients with sleep apnoea. However, the molecular and cellular mechanisms of how IH causes these changes is unclear and under investigation. This review focuses on the most recent findings addressing these mechanisms. It includes a discussion of the contribution of the nervous system, circulating and vascular factors, inflammatory mediators and transcription factors to IH-induced cardiovascular disease. It also highlights the importance of reactive oxygen species as a primary mediator of the systemic and pulmonary hypertension that develops in response to exposure to IH. PMID:19818095

Bosc, Laura V González; Resta, Thomas; Walker, Benjimen; Kanagy, Nancy L

2009-10-10

43

Mechanisms of obesity-induced hypertension  

Microsoft Academic Search

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

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

2010-01-01

44

Worsened hypertension control induced by aripiprazole  

PubMed Central

Aripiprazole is widely used in the treatment of schizophrenia and bipolar disorders. Although antipsychotics generally have hypotensive effects, two cases were identified that demonstrated hypertension during the switch from other antipsychotics to aripiprazole. The hypertensive state of these patients recovered after switching back to other antipsychotics, and these cases suggest that aripiprazole may lead to hypertension.

Yasui-Furukori, Norio; Fujii, Akira

2013-01-01

45

Taurine Prevents Hypertension and Increases Exercise Capacity in Rats With Fructose-Induced Hypertension  

Microsoft Academic Search

BackgroundFructose-induced hypertension was used to test the hypothesis that taurine supplementation and\\/or exercise can prevent hypertension and increase exercise capacity.MethodsFive groups of 15 Sprague–Dawley rats were allocated and designated as control, high fructose–fed (fructose), high fructose–fed plus exercise (FE), high fructose–fed plus 2% taurine supplement (FT) and high fructose–fed plus 2% taurine supplement and exercise (FET) groups. Noninvasive systolic blood

Mizanur M. Rahman; Hye-Min Park; Shang-Jin Kim; Hyeon-Kyu Go; Gi-Beum Kim; Chul-Un Hong; Young-Up Lee; Sung-Zoo Kim; Jin-Shang Kim; Hyung-Sub Kang

2011-01-01

46

Low incidence of hypertensive disorders of pregnancy in women treated with spiramycin for toxoplasma infection  

PubMed Central

Aims Toxoplasma infection in pregnancy is usually treated with long-term administration of the macrolide spiramycin to prevent fetal malformations. We had empirically observed that treated patients seldom developed pregnancy-induced hypertension (PIH), a common and severe disorder of pregnancy whose aetiology and pathogenesis are still debated. Some clinical and experimental data suggest that infection could play a role in its development. Methods To test this hypothesis, we studied a cohort of 417 pregnant women treated with spiramycin because of seroconversion for Toxoplasma gondii and 353 low-risk women who did not take any antibiotic during pregnancy. PIH was defined as blood pressure >140/90 mmHg on two or more occasions, occurring after 20 weeks of gestational age. Results Seventeen (5.2%) women in the control group developed PIH compared with two (0.5%) in the case group. The odds of developing the disease were significantly lower in the treated subjects (odds ratio =0.092, 95% confidence interval 0.021, 0.399; P < 0.001). Conclusions Our results suggest that antibiotic treatment during pregnancy can reduce the incidence of PIH, thus opening new perspectives in its prevention and therapy.

Todros, T; Verdiglione, P; Ogge, G; Paladini, D; Vergani, P; Cardaropoli, S

2006-01-01

47

Platelet-Activating Factor and Bacteremia-Induced Pulmonary Hypertension  

Microsoft Academic Search

Background. Acute lung injury is a common complication of gram-negative sepsis. Pulmonary hypertension and increased lung vascular permeability are central features of lung injury following experimental bacteremia. Platelet-activating factor is a prominent proinflammatory mediator during bacterial sepsis. Our previous studies have demonstrated that exogenous administration of platelet-activating factor (PAF) induces pulmonary edema without causing pulmonary hypertension. Interestingly, inhibition of PAF

Leonardo C Clavijo; Mary B Carter; Paul J Matheson; Lisa A Wills-Frank; Mark A Wilson; William B Wead; R. Neal Garrison

2000-01-01

48

Excellent Tolerance to Cilnidipine in Hypertensives with Amlodipine - Induced Edema  

PubMed Central

Background: Ankle edema is a common adverse effect of amlodipine, an L-type calcium channel blocker (CCB). Cilnidipine is a newer L/N-type CCB, approved for treatment of essential hypertension. Aim: This study was designed to determine whether cilnidipine can produce resolution of amlodipine-induced edema while maintaining adequate control of hypertension. Materials and Methods: A prospective study was performed on 27 patients with essential hypertension with amlodipine-induced edema. Concomitant nephropathy, cardiac failure, hepatic cirrhosis, or other causes of edema, and secondary hypertension were excluded by appropriate tests. Amlodipine therapy was substituted in all the cases with an efficacy-equivalent dose of cilnidipine. Clinical assessment of ankle edema and measurement of bilateral ankle circumference, body weight, blood pressure, and pulse rate were performed at onset of the study and after 4 weeks of cilnidipine therapy. Results: At completion of the study, edema had resolved in all the patients. There was a significant decrease in bilateral ankle circumference and body weight (P < 0.001). There was no significant change in mean arterial blood pressure and pulse rate. Conclusions: Therapy with cilnidipine resulted in complete resolution of amlodipine-induced edema in all the cases without significant worsening of hypertension or tachycardia. Cilnidipine is an acceptable alternative antihypertensive for patients with amlodipine-induced edema.

Shetty, Ranjan; Vivek, G; Naha, Kushal; Tumkur, Anil; Raj, Abhinav; Bairy, K L

2013-01-01

49

The Pih1-Tah1 Cochaperone Complex Inhibits Hsp90 Molecular Chaperone ATPase Activity*  

PubMed Central

Hsp90 (heat shock protein 90) is an ATP-dependent molecular chaperone regulated by collaborating proteins called cochaperones. This machinery is involved in the conformational activation of client proteins like signaling kinases, transcription factors, or ribonucleoproteins (RNP) such as telomerase. TPR (TetratricoPeptide Repeat)-containing protein associated with Hsp90 (Tah1) and protein interacting with Hsp90 (Pih1) have been identified in Saccharomyces cerevisiae as two Hsp90 cochaperones involved in chromatin remodeling complexes and small nucleolar RNP maturation. Tah1 possesses a minimal TPR domain and binds specifically to the Hsp90 C terminus, whereas Pih1 displays no homology to other protein motifs and has been involved in core RNP protein interaction. While Pih1 alone was unstable and was degraded from its N terminus, we showed that Pih1 and Tah1 form a stable heterodimeric complex that regulates Hsp90 ATPase activity. We used different biophysical approaches such as analytical ultracentrifugation, microcalorimetry, and noncovalent mass spectrometry to characterize the Pih1-Tah1 complex and its interaction with Hsp90. We showed that the Pih1-Tah1 heterodimer binds to Hsp90 with a similar affinity and the same stoichiometry as Tah1 alone. However, the Pih1-Tah1 complex antagonizes Tah1 activity on Hsp90 and inhibits the chaperone ATPase activity. We further identified the region within Pih1 responsible for interaction with Tah1 and inhibition of Hsp90, allowing us to suggest an interaction model for the Pih1-Tah1/Hsp90 complex. These results, together with previous reports, suggest a role for the Pih1-Tah1 cochaperone complex in the recruitment of client proteins such as core RNP proteins to Hsp90.

Eckert, Kelvin; Saliou, Jean-Michel; Monlezun, Laura; Vigouroux, Armelle; Atmane, Noureddine; Caillat, Christophe; Quevillon-Cheruel, Sophie; Madiona, Karine; Nicaise, Magali; Lazereg, Sylvie; Van Dorsselaer, Alain; Sanglier-Cianferani, Sarah; Meyer, Philippe; Morera, Solange

2010-01-01

50

Effect of Lutein on L-NAME-Induced Hypertensive Rats  

PubMed Central

We investigated the antihypertensive effect of lutein on NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Daily oral administration of L-NAME (40 mg/kg)-induced a rapid progressive increase in mean arterial pressure (MAP). L-NAME significantly increased MAP from the first week compared to that in the control and reached 193.3±9.6 mmHg at the end of treatment. MAP in the lutein groups was dose-dependently lower than that in the L-NAME group. Similar results were observed for systolic and diastolic blood pressure of L-NAME-induced hypertensive rats. The control group showed little change in heart rate for 3 weeks, whereas L-NAME significantly reduced heart rate from 434±26 to 376±33 beats/min. Lutein (2 mg/kg) significantly prevented the reduced heart rate induced by L-NAME. L-NAME caused hypertrophy of heart and kidney, and increased plasma lipid peroxidation four-fold but significantly reduced plasma nitrite and glutathione concentrations, which were significantly prevented by lutein in a dose-dependent manner. These findings suggest that lutein affords significant antihypertensive and antioxidant effects against L-NAME-induced hypertension in rats.

Sung, Ji Hoon; Jo, Young Soo; Kim, Su Jin; Ryu, Jeong Soo; Kim, Myung Chul; Ko, Hyun Ju

2013-01-01

51

Migraine-Asthma Comorbidity and Risk of Hypertensive Disorders of Pregnancy  

PubMed Central

Background. To evaluate the association of migraine and asthma and to estimate the risk of hypertensive disorders of pregnancy in relation to maternal comorbid migraine and asthma. Methods. Reproductive age women (N = 3.731) were interviewed during early pregnancy. At the time of interview, we ascertained participants' migraine and asthma status. From medical records, we collected information to allow the diagnosis of pregnancy-induced hypertension (PIH) and preeclampsia. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression procedures. Results. After adjusting for confounders, migraineurs had 1.38-fold increased odds of asthma as compared with nonmigraineurs (95% CI 1.09–1.38). The odds of hypertensive disorders of pregnancy were highest among women with comorbid migraine-asthma. The ORs for PIH preeclampsia and the two disorders combined were 2.53 (95% CI 1.39–4.61), 3.53 (95% CI 1.51–8.24), and 2.64 (95% CI 1.56–4.47), respectively, for women with comorbid migraine-asthma as compared with those who had neither disorder. Conclusion. These findings confirm prior reports and extend the literature by documenting particularly high odds of pregnancy-induced hypertension and preeclampsia among women with comorbid migraine-asthma. Increased knowledge about the prevalence and sequelae of comorbidities during pregnancy may lead to improved symptom management and perinatal outcomes.

Czerwinski, Stefanie; Gollero, Jolana; Qiu, Chunfang; Sorensen, Tanya K.; Williams, Michelle A.

2012-01-01

52

Pyridoxal isonicotinoyl hydrazone (PIH) prevents copper-mediated in vitro free radical formation  

Microsoft Academic Search

Pyridoxal isonicotinoyl hydrazone (PIH) is an iron chelator with antioxidant activity, low toxicity and is useful in the experimental treatment of iron-overload diseases. Previous studies on x-ray diffraction have revealed that PIH also forms a complex with Cu(II). Since the main drug of choice for the treatment of Wilson's disease, d-penicillamine, causes a series of side effects, there is an

Marcelo Hermes-Lima; Márcia S. Gonçalves; Roberto G. Andrade

2001-01-01

53

Estradiol metabolites attenuate monocrotaline-induced pulmonary hypertension in rats.  

PubMed

Pulmonary arterial hypertension (PH) is a deadly disease characterized by pulmonary arterial vasoconstriction and hypertension, pulmonary vasculature remodeling, and right ventricular hypertrophy. Our previous in vivo studies, performed in several models of cardiac, vascular, and/or renal injury, suggest that the metabolites of 17beta-estradiol may inhibit vascular and cardiac remodeling. The goal of this study was to determine whether 2-methoxyestradiol (2ME), major non-estrogenic estradiol metabolite, prevents the development and/or retards the progression of monocrotaline (MCT)-induced PH. First, a total of 27 male Sprague Dawley rats were injected with distillated water (Cont, n=6) or monocrotaline (MCT; 60 mg/kg, i.p.; n=21). Subsets of MCT animals (n=7 per group) received 2ME or its metabolic precursor 2-hydroxyestradiol (2HE; 10 microg/kg/h via osmotic minipumps) for 21 days. Next, an additional set (n=24) of control and MCT rats was monitored for 28 days, before right ventricular peak systolic pressure (RVPSP) was measured. Some pulmonary hypertensive animals (n=8) were treated with 2ME (10 microg/kg/h) beginning from day 14 after MCT administration. MCT caused pulmonary hypertension (ie, increased right ventricle/left ventricle+septum [RV/LV+S] ratio and wall thickness of small-sized pulmonary arteries, and elevated RVPSP) and produced high and late (days 22 to 27) mortality. Pulmonary hypertension was associated with strong proliferative response (PCNA staining) and marked inflammation (ED1+cells) in lungs. Both metabolites significantly attenuated the RV/LV+S ratio and pulmonary arteries media hypertrophy and reduced proliferative and inflammatory responses in the lungs. Furthermore, in diseased animals, 2ME (given from day 14 to 28) significantly decreased RVPSP, RV/LV+S ratio and wall thickness, and reduced mortality by 80% (mortality rate: 62.5% vs. 12.5%, MCT vs. MCT+2ME day 14 to 28). This study provides the first evidence that 2ME, a major non-estrogenic, non-carcinogenic metabolite of estradiol, prevents the development and retards the progression of monocrotaline-induced pulmonary hypertension. Further evaluation of 2ME for management of pulmonary arterial hypertension is warranted. PMID:16160593

Tofovic, Stevan P; Salah, Eman M; Mady, Hussam H; Jackson, Edwin K; Melhem, Mona F

2005-10-01

54

Elastase-induced intracranial aneurysms in hypertensive mice  

PubMed Central

Mechanisms of formation and growth of intracranial aneurysms are poorly understood. To investigate the pathophysiology of intracranial aneurysms, an animal model of intracranial aneurysm yielding high incidence of large aneurysm formation within a short incubation period is needed. We combined two well-known clinical factors associated with human intracranial aneurysms—hypertension and the degeneration of elastic lamina— to induce intracranial aneurysm formation in mice. Roles of matrix metalloproteinases (MMPs) in this model were investigated utilizing doxycycline, a broad-spectrum MMP inhibitor, and MMP knockout mice. Hypertension was induced by continuous infusion of angiotensin-II for two weeks. The disruption of elastic lamina was achieved by a single stereotaxic injection of elastase into the cerebrospinal fluid at the right basal cistern. 77% of the mice that received 35 milli-units of elastase and 1000 ng/kg/min angiotensin-II developed intracranial aneurysms in two weeks. There were dose-dependent effects of elastase and angiotensin-II on the incidence of aneurysms. Histologically, intracranial aneurysms observed in this model closely resembled human intracranial aneurysms. Doxycycline, a broad-spectrum MMP inhibitor, reduced the incidence of aneurysm to 10%. MMP-9 knockout mice, but not MMP-2 knockout mice, had reduced the incidence of intracranial aneurysms. In summary, a stereotaxic injection of elastase into the basal cistern in hypertensive mice resulted in intracranial aneurysms that closely resembled human intracranial aneurysms. The intracranial aneurysm formation in this model appeared to be dependent on MMP activation.

Nuki, Yoshitsugu; Tsou, Tsung-Ling; Kurihara, Chie; Kanematsu, Miyuki; Kanematsu, Yasuhisa; Hashimoto, Tomoki

2009-01-01

55

Racial Differences in Stress-Induced Cardiovascular Reactivity and Hypertension: Current Status and Substantive Issues  

Microsoft Academic Search

Essential hypertension is perhaps the number-one health problem of Black Americans. Research has indicated that stress-induced cardiovascular hyperreactivity may be a significant contributor to essential hypertension. The high prevalence of hypertension among Blacks suggests that this group, in comparison with Whites, may be particularly susceptible to cardiovascular hyperreactivity. The first portion of this article reviews research to date that has

Norman B. Anderson

1989-01-01

56

Calcimimetic NPS R-568 induces hypotensive effect in spontaneously hypertensive rats  

Microsoft Academic Search

Background: The discovery of calcium receptors and calcimimetics created the possibility of “pharmacologic parathyroidectomy” (phPTX), which decreased secretion of parathormone (PTH). Parathyroid glands of spontaneously hypertensive rats (SHR) and of patients with primary hyperparathyroidism and hypertension secrete parathyroid hypertensive factor (PHF). Parathyroidectomy decreases blood pressure in these rats and in patients. The present study determined whether phPTX induced by calcimimetics

Apolonia Rybczyníska; Konrad Boblewski; Artur Lehmann; Czeslawa Orlewska; Henryk Foks; Krystyna Drewnowska; Anzelm Hoppe

2005-01-01

57

Hypertension  

MedlinePLUS

... hypertension: Treatment. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook ... and diagnosis. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook ...

58

Atenolol in the treatment of pregnancy-induced hypertension.  

PubMed Central

1 The pharmacological properties of atenolol suggest its possible usefulness in pregnancy-induced hypertension. The pharmacokinetics of atenolol in the pregnant woman, concentrations in cord blood, and its effects on maternal blood pressure and the foetus, are evaluated. 2 We studied 13 pregnant women with hypertension, most of them uncontrolled on methyldopa. Whole blood concentrations and urinary excretion of the drug were measured over 24 h following a 100 mg dose. Effects on maternal blood pressure, pulse rate and foetal heart rate and cardiotocograph were compared for the 4 days before treatment and the first 4 days of treatment. The birth weights and Apgar scores of the babies were recorded. 2 The pharmacokinetics of atenolol (plasma half-life of about 8 h) in pregnant women do not differ from the findings in the non-pregnant. The levels of atenolol in the cord blood were confirmed as approximately equal to those in the maternal blood. 4 In the ten women in whom blood pressure was assessed a small significant fall in blood pressure was observed. 5 A 5% mean fall in foetal heart rate resulted but in one case was a rate below 120 beats/min recorded. There was no evidence of depression of the stress response of the foetal heart. Apgar scores 5 min post partum were satisfactory. 6 Atenolol appears to be safe for use in hypertensive pregnancies. Its effectiveness as an antihypertensive agent in pregnancy requires further controlled evaluation.

Thorley, K J; McAinsh, J; Cruickshank, J M

1981-01-01

59

Atenolol in the treatment of pregnancy-induced hypertension.  

PubMed

1 The pharmacological properties of atenolol suggest its possible usefulness in pregnancy-induced hypertension. The pharmacokinetics of atenolol in the pregnant woman, concentrations in cord blood, and its effects on maternal blood pressure and the foetus, are evaluated. 2 We studied 13 pregnant women with hypertension, most of them uncontrolled on methyldopa. Whole blood concentrations and urinary excretion of the drug were measured over 24 h following a 100 mg dose. Effects on maternal blood pressure, pulse rate and foetal heart rate and cardiotocograph were compared for the 4 days before treatment and the first 4 days of treatment. The birth weights and Apgar scores of the babies were recorded. 2 The pharmacokinetics of atenolol (plasma half-life of about 8 h) in pregnant women do not differ from the findings in the non-pregnant. The levels of atenolol in the cord blood were confirmed as approximately equal to those in the maternal blood. 4 In the ten women in whom blood pressure was assessed a small significant fall in blood pressure was observed. 5 A 5% mean fall in foetal heart rate resulted but in one case was a rate below 120 beats/min recorded. There was no evidence of depression of the stress response of the foetal heart. Apgar scores 5 min post partum were satisfactory. 6 Atenolol appears to be safe for use in hypertensive pregnancies. Its effectiveness as an antihypertensive agent in pregnancy requires further controlled evaluation. PMID:7332738

Thorley, K J; McAinsh, J; Cruickshank, J M

1981-11-01

60

Inhibition of phosphodiesterase-1 attenuates cold-induced pulmonary hypertension.  

PubMed

Chronic exposure to cold caused pulmonary arterial hypertension (cold-induced pulmonary hypertension [CIPH]) and increased phosphodiesterase-1C (PDE-1C) expression in pulmonary arteries (PAs) in rats. The purpose of this study is to investigate a hypothesis that inhibition of PDE-1 would decrease inflammatory infiltrates and superoxide production leading to attenuation of CIPH. Three groups of male rats were exposed to moderate cold (5±1°C) continuously, whereas 3 groups were maintained at room temperature (23.5±1°C, warm; 6 rats/group). After 8-week exposure to cold, 3 groups in each temperature condition received continuous intravenous infusion of 8-isobutyl-methylxanthine (8-IBMX) (PDE-1 inhibitor), apocynin (NADPH oxidase inhibitor) or vehicle, respectively, for 1 week. Cold exposure significantly increased right-ventricular systolic pressure compared with warm groups (33.8±3.2 versus 18.6±0.3 mm Hg), indicating that animals developed CIPH. Notably, treatment with 8-IBMX significantly attenuated the cold-induced increase in right ventricular pressure (23.5±1.8 mm Hg). Cold exposure also caused right-ventricular hypertrophy, whereas 8-IBMX reversed cold-induced right ventricular hypertrophy. Cold exposure increased PDE-1C protein expression, macrophage infiltration, NADPH oxidase activity, and superoxide production in PAs and resulted in PA remodeling. 8-IBMX abolished cold-induced upregulation of PDE-1C in PAs. Interestingly, inhibition of PDE-1 eliminated cold-induced macrophage infiltration, NADPH oxidase activation, and superoxide production in PAs and reversed PA remodeling. Inhibition of NADPH oxidase by apocynin abolished cold-induced superoxide production and attenuated CIPH and PA remodeling. In conclusion, inhibition of PDE-1 attenuated CIPH and reversed cold-induced PA remodeling by suppressing macrophage infiltration and superoxide production, suggesting that upregulation of PDE-1C expression may be involved in the pathogenesis of CIPH. PMID:23319544

Crosswhite, Patrick; Sun, Zhongjie

2013-01-14

61

Hypertension.  

PubMed

An estimated 58 million Americans are at increased risk of morbidity and premature death due to high blood pressure (BP) and require some type of therapy or systematic monitoring. This article focuses on recent advances in our understanding of the pathogenesis of hypertension, new approaches to the diagnosis and treatment of secondary hypertension, and current views of the most appropriate nonpharmacologic and pharmacologic therapy for essential hypertension. In view of the extremely high prevalence of the disorder, emphasis is placed on efficient and cost-effective strategies for diagnosing and managing the hypertensive patient. Recent evidence indicates that nonpharmacologic therapy, including dietary potassium and calcium supplements, reduction of salt intake, weight loss for the obese patient, regular exercise, a diet high in fiber and low in cholesterol and saturated fats, smoking cessation, and moderation of alcohol consumption produces significant sustained reductions in BP while reducing overall cardiovascular risk. Accordingly, nonpharmacologic antihypertensive therapy should be included in the treatment of all hypertensive patients. In persons with mild hypertension, nonpharmacologic approaches may adequately reduce BP, thereby avoiding the expense and potential side effects of drug therapy. In patients with more severe hypertension, nonpharmacologic therapy, used in conjunction with pharmacologic therapy, can reduce the dosage of antihypertensive medications necessary for BP control. Patients treated with nonpharmacologic therapy only should be followed closely, and if BP control is not satisfactory, drug therapy should be added. The large number of drugs available for use in hypertension treatment, coupled with our rapidly expanding knowledge of the pathophysiology of hypertension and of the adverse effects of these drugs in individual patient groups, make it possible to individualize antihypertensive treatment. When used as monotherapy, most agents effectively lower BP in the majority of patients with mild or moderate essential hypertension. Thus, a single agent from one of four classes: diuretics, angiotensin-converting enzyme inhibitors, calcium channel blockers, and beta-adrenergic blockers, usually provides effective BP control with minimal side effects in most patients. Therapy should be initiated with the agent most likely to be effective in BP lowering and best tolerated. If the initial agent is ineffective at maximal recommended therapeutic doses or has undue side effects, an alternative agent from another class should be tried. When monotherapy is unsuccessful, a second agent, usually of a different mechanism of action, should be PMID:2565199

Oparil, S; Calhoun, D A

1989-03-01

62

PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription.  

PubMed

PIH1D1 is the defining component of the R2TP complex. Recently, R2TP has been reported to stabilize mTOR (mammalian target of rapamycin), an important regulator of cell growth and protein synthesis. Two complexes of mTOR, mTORC1 and mTORC2, have been identified. We demonstrate that immunoprecipitation (IP) of PIH1D1 results in the co-IP of Raptor (mTORC1 specific), but not Rictor (mTORC2 specific), and that knockdown of PIH1D1 decreases mTORC1 assembly, S6 kinase phosphorylation (indicator of mTORC1 activity), and rRNA transcription without affecting mTORC2 in human breast cancer MCF-7 cells. In addition, we provide evidence that PIH1D1 is overexpressed in various breast cancer cell lines. These findings collectively suggest that PIH1D1 may have an important role in mTORC1 regulation in breast cancers. PMID:24036451

Kamano, Yuya; Saeki, Makio; Egusa, Hiroshi; Kakihara, Yoshito; Houry, Walid A; Yatani, Hirofumi; Kamisaki, Yoshinori

2013-09-11

63

Steroid glaucoma: corticosteroid-induced ocular hypertension in cats.  

PubMed

This study was undertaken to develop a feline model of corticosteroid-induced ocular hypertension. In the first experiment, eight cats were selected whose intraocular pressure (17 +/- 0.4 mmHg) was consistently below the mean baseline intraocular pressure of our colony (24 +/- 0.5) during the preceding 2 months. Unilateral twice or thrice daily topical application of 10 microliters 1% dexamethasone sodium phosphate caused a gradual intraocular pressure increase that became significant (P less than 0.05) within 2-3 weeks. There was no significant change in body weight, but several eyes developed cataracts. Similar results were obtained with treatment of normotensive cat eyes with dexamethasone, or with 1.0% prednisolone acetate (PredForte) twice a day. Topical application of PGF2 alpha-1-isopropyl ester (0.1 or 0.25 microgram PG equivalent) to such steroid-treated eyes yielded significant intraocular pressure reduction and pupillary miosis, similar in magnitude to those exhibited by normal eyes. When dexamethasone treatment was reduced to once daily, after prolonged twice daily treatment, intraocular pressure decreased only slightly within 10 days. When dexamethasone treatment was stopped, intraocular pressure declined to normal levels within 6-7 days. These findings show that adult cat eyes develop steroid-induced ocular hypertension that is maintained and reversible. As opposed to previous findings on rabbits, steroid-induced feline ocular hypertension appears to be a good model for this clinical condition and may be suitable for the testing of potential glaucoma drugs. PMID:1559550

Zhan, G L; Miranda, O C; Bito, L Z

1992-02-01

64

Oleanolic acid prevents glucocorticoid-induced hypertension in rats.  

PubMed

The present study was designed to evaluate the antihypertensive activity of oleanolic acid isolated from Viscum articulatum, Burm. (Loranthaceae) in glucocorticoid (dexamethasone)-induced hypertension in rats and to propose a probable mechanism of action for this effect. Male Wistar rats (300-350?g) received dexamethasone (20??g/kg/day?s.c.) or saline (vehicle) for 10?days. In a prevention study, the rats received oleanolic acid (60?mg/kg i.p.) for 5?days, followed by dexamethasone or saline for 10?days. During this period the systolic blood pressure and body weight were evaluated on alternate days. At the end of the experiment, the weight of the thymus gland, plasma nitrate/nitrite (nitric oxide metabolites) concentration and cardiac lipid peroxidation value were determined. Oleanolic acid (60?mg/kg i.p.) significantly prevented a rise in the systolic blood pressure and cardiac lipid peroxidation level after administration of dexamethasone (p?induced change in body and thymus weights. The decrease in concentration of plasma nitrate/nitrite due to dexamethasone was prevented significantly in the group treated with oleanolic acid (p?induced hypertension in rats, which may be attributed to its antioxidant and nitric oxide releasing action. PMID:21953707

Bachhav, Sagar S; Patil, Savita D; Bhutada, Mukesh S; Surana, Sanjay J

2011-02-24

65

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

PubMed Central

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.

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

2009-01-01

66

Cardiovascular effects induced by linalool in normotensive and hypertensive rats.  

PubMed

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

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

67

Deletion of Inducible Nitric Oxide Synthase Provides Cardioprotection in Mice With 2Kidney, 1Clip Hypertension  

Microsoft Academic Search

Inducible NO synthase (iNOS) has been implicated in the pathogenesis of hypertension and target organ damage. We hypothesized that induction of iNOS contributes to left ventricular (LV) hypertrophy and dysfunction in mice with 2-kidney, 1-clip hypertension. Deletion of iNOS diminishes oxidative stress, thereby attenuating LV hypertrophy and enhancing cardiac performance. 2-Kidney, 1-clip hypertension was induced in mice lacking iNOS and

Ying Sun; Oscar A. Carretero; Jiang Xu; Nour-Eddine Rhaleb; James J. Yang; Patrick J. Pagano; Xiao-Ping Yang

68

Hypertension  

Microsoft Academic Search

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

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

69

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  

PubMed Central

Background The complications of hypertension cause severe health problems in rural areas in China. We (i) screened the major factors inducing hypertensive complications and provided intervention measures; and (ii) verified the efficacy of the New Rural Cooperative Medical Scheme (NRCMS; a medical insurance scheme for rural residents) for hypertension management. Methods A survey was conducted in the villages of Yunnan (an underdeveloped province in southwest China). The NRCMS was initiated there in 2005. Data were collected through questionnaires, physical examination, electrocardiography, as well as blood and urine tests. To detect factors inducing hypertension complications, a generalized estimating equations model was developed. Multivariable logistic regression was used to analyze influencing factors for hypertension control. Results Poor management of hypertension was observed in women. Being female, old, poorly educated, a smoker, ignorant of the dangerousness of hypertension, and having uncontrolled hypertension made patients more prone to hypertension complications. Combination therapy with ?2 drugs helped control hypertension, but most rural patients disliked multidrug therapy because they considered it to be expensive and inconvenient. The NRCMS contributed little to reduce the prevalence of complications and improve control of hypertension. Conclusions The present study suggested that the NRCMS needs to be reformed to concentrate on early intervention in hypertension and to concentrate on women. To increase hypertension control in rural areas in China, compound products containing effective and inexpensive drugs (and not multidrug therapy) are needed.

2011-01-01

70

Laser-Induced Ocular Hypertension in Albino CD-1 Mice  

PubMed Central

Purpose. To establish a laser-induced model of ocular hypertension (LIOH) in albino CD-1 mice and to characterize the sequence of pathologic events triggered by intraocular pressure (IOP) elevation. Methods. LIOH was induced unilaterally in CD-1 mice by laser photocoagulation of limbal and episcleral veins 270° to 300° circumferentially, sparing the nasal aspect and the long ciliary arteries. IOP was measured with a rebound tonometer. Hematoxylin and eosin-stained plastic sections were used for morphometric analysis of retinal layers, and retinal whole-mounts were immunostained with anti-Brn-3b to quantify retinal ganglion cell (RGC) gene expression ion and density. Axonal and myelin morphologies were characterized using appropriate antibodies, and axon counts were obtained from paraphenylenediamine-stained optic nerve sections. Results. LIOH resulted in IOP doubling within 4 hours after laser treatment, which returned to normal by 7 days. Axon degenerative changes, reactive plasticity, and aberrant regrowth were detected at the optic nerve head (ONH) as early as 4 days after treatment. By 7 days, axon number was significantly reduced in the myelinated optic nerve, with concurrent signs of myelin degradation. At 14 days, Brn-3b+ RGC density was reduced, with neuronal loss confined to the RGC layer and no apparent effects on other retinal layers. Conclusions. Laser photocoagulation of limbal and episcleral veins induces transient ocular hypertension in albino CD-1 mice. The ensuing retinal and optic nerve pathologic events recapitulated key features of glaucoma and placed ONH RGC axon responses as an early manifestation of damage. LIOH in albino mice may be useful as a mouse model to examine mechanisms of RGC and axon glaucomatous injury.

Sretavan, David

2010-01-01

71

Taurocholate induced gastric mucosal injuries in experimental portal hypertension.  

PubMed Central

The susceptibility of the gastric mucosa to injury by topical sodium taurocholate (40 mmol/l) in hydrochloric acid (150 mmol/l) was studied in prehepatic and cirrhotic rat models of portal hypertension. Portal venous pressure was increased in rats who had undergone partial portal vein ligation compared with rats that had undergone sham operation on days 3, 7, and 28 after operation (20.6 (0.9), 14.8 (0.8), and 11.3 (0.5) mm Hg v 7.3 (0.7), 7.3 (0.6), and 8.2 (0.2) mmHg respectively (mean (SEM)). At day 3 gastric mucosal injuries were increased in rats with partial portal vein ligation compared with sham operated rats (55.3 (9.4) vs 22.3 (10.5) mm2, p = 0.006), but at the later time intervals there was no significant difference in injuries between the two groups. In rats with carbon tetrachloride induced hepatic cirrhosis, portal pressure was increased (15.6 (1.0) v 6.7 (0.6) mmHg), but again there was no significant difference in mucosal injuries relative to control animals. We conclude that gastric mucosal defence mechanisms are impaired in acute but not chronic experimental portal hypertension.

Angerson, W J; Geraghty, J G; Carter, D C

1992-01-01

72

Genistein, a Phytoestrogen, Attenuates Monocrotaline-Induced Pulmonary Hypertension  

Microsoft Academic Search

Background: Pulmonary hypertension is characterized by high pulmonary blood pressure, vascular remodeling, and right ventricular hypertrophy. Although recent studies suggest that an imbalance between endothelial mediators on pulmonary vasculature may contribute to the development of pulmonary hypertension, the pathogenesis is not fully understood and the treatment of pulmonary hypertension is still unresolved. Objective: The purpose of this study was to

Noriyuki Homma; Yoshiteru Morio; Hideki Takahashi; Akihito Yamamoto; Tsutomu Suzuki; Koichi Sato; Masashi Muramatsu; Yoshinosuke Fukuchi

2006-01-01

73

Portal hypertension triggers local activation of inducible nitric oxide synthase gene in colonic mucosa.  

PubMed

Recently a new clinical entity "portal hypertensive colopathy" has been reported. It involves vascular abnormalities and bleeding. Because nitric oxide may mediate these changes, we studied whether portal hypertension affects nitric oxide synthase in portal hypertensive colonic mucosa. In portal hypertensive and sham-operated rats the following studies were done: (1) colonic mucosal blood flow, (2) quantitative histologic examination, (3) reverse transcription-polymerase chain reaction for nitric oxide synthase mRNA, (4) nitric oxide synthase activity assay, and (5) immunostaining for nitric oxide synthase. In portal hypertensive rats, colonic mucosal blood flow and the number of submucosal veins were significantly increased in comparison to sham-operated rats. The mRNA expression and enzyme activity for inducible nitric oxide synthase (but not constitutive nitric oxide synthase) were significantly increased in portal hypertensive rats. Fluorescence signal intensity for inducible nitric oxide synthase in endothelia of mucosal and submucosal veins was significantly higher in portal hypertensive rats than in sham-operated rats. Portal hypertension activates inducible nitric oxide synthase gene and protein in colonic mucosal vessels. The excess of nitric oxide generated by overexpressed inducible nitric oxide synthase may play an important role in the development of vascular and hemodynamic abnormalities characterizing portal hypertensive colopathy. PMID:9834352

Ohta, M; Kaviani, A; Tarnawski, A S; Itani, R; Sugimachi, K; Sarfeh, I J

74

Losartan-antioxidant hybrids: novel molecules for the prevention of hypertension-induced cardiovascular damage.  

PubMed

We report the first examples of a new series of antioxidant-sartan hybrids (AO-sartans), which were made by adding an antioxidant fragment to the hydroxymethyl side chain of losartan. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect with increased antioxidant ability. In hypertensive rats, these compounds show properties that suggest they may be more useful than losartan for controlling hypertension and preventing hypertension-induced cardiovascular damage. PMID:19863054

García, Gonzalo; Rodríguez-Puyol, Manuel; Alajarín, Ramón; Serrano, Isabel; Sánchez-Alonso, Patricia; Griera, Mercedes; Vaquero, Juan J; Rodríguez-Puyol, Diego; Alvarez-Builla, Julio; Díez-Marqués, María L

2009-11-26

75

Oxidative Stress in a Rat Model of Obesity-Induced Hypertension  

Microsoft Academic Search

Abstract—The mechanisms,underlying the development,of hypertension in obesity are not yet fully understood. We recently reported the development,of hypertension in a rat model,of diet-induced obesity. When Sprague-Dawley rats (n560) are fed a moderately high fat diet (32 kcal% fat) for 10 to 16 weeks, approximately half of them develop obesity (obesity-prone [OP] group) and mild hypertension (15863.4 mm Hg systolic pressure),

Russell L. Prewitt; Anca D. Dobrian; Michael J. Davies; Suzanne D. Schriver; Thomas J. Lauterio

2010-01-01

76

Effect of exercise training on liver antioxidant status of deoxycorticosterone acetate salt induced hypertensive rats.  

PubMed

Several animal models have been developed to study the pathogenesis of hypertension. Deoxycorticosterone acetate (DOCA) salt induced hypertensive rats are adrenal models used to mimic human Conn's syndrome. Because previous studies showed a beneficial effect of chronic exercise (swimming) on the development of arterial hypertension in spontaneously hypertensive rats (which appears similar to human essential hypertension), we decided to evaluate the effects of swimming on DOCA-salt induced hypertension and liver antioxidant status. Therefore, the aim of this experiment was to study whether the swim training would improve hypertension and liver antioxidant status in DOCA-salt rats. DOCA-salt rats and control Sprague-Dawley rats were trained to swim 1 h/day, 5 days/week for 6 weeks and were sacrificed 48 h after the last exercise period. Systolic blood pressure was recorded before the sacrifice, and liver antioxidant status was evaluated in hepatic homogenates after the sacrifice. Swim exercise did not decrease systolic blood pressure in control and DOCA-salt rats but induced changes in liver activities of antioxidant enzymes, showing that exercise provoked liver oxidative stress in control and DOCA-salt rats. In comparison with our previous studies using spontaneously hypertensive rats, we conclude that the beneficial effects of chronic exercise on systolic blood pressure in rats are dependent on strain and the type of experimental hypertension. PMID:12774853

Elhaïmeur, Fatiha; Courderot-Masuyer, Carol; Nicod, Laurence; Bobillier-Chaumont, Sylvie; Robin, Sophie; Richert, Lysiane; Berthelot, Alain

2003-05-01

77

Role of calcitonin gene-related peptide in hypertension-induced renal damage.  

PubMed

Calcitonin gene-related peptide, a potent vasodilator neuropeptide, is localized in perivascular sensory nerves. We have reported that alpha-calcitonin gene-related peptide knockout mice have elevated baseline blood pressure and enhanced hypertension-induced renal damage compared with wild-type controls. Thus, the aim of this study was to determine the mechanism and functional significance of this increased hypertension-induced renal damage. We previously demonstrated by telemetric recording that the deoxycorticosterone-salt protocol produces a 35% increase in mean arterial pressure in both alpha-calcitonin gene-related peptide knockout and wild-type mice. Both strains of mice were studied at 0, 14, and 21 days after deoxycorticosterone-salt hypertension. Renal sections from hypertensive wild-type mice showed no pathological changes at any time point studied. However, on days 14 and 21, hypertensive knockout mice displayed progressive increases in glomerular proliferation, crescent formation, and tubular protein casts, as well as the inflammatory markers intercellular adhesion molecule-1, vascular adhesion molecule-1, and monocyte chemoattractant protein-1. There was a significant increase in 24-hour urinary isoprostane, a marker of oxidative stress-induced lipid peroxidation, levels at days 14 and 21 in the hypertensive knockout compared with hypertensive wild-type mice. Urinary microalbumin was significantly higher (2-fold) at day 21 and creatinine clearance was significantly decreased 4-fold in the hypertensive knockout compared with hypertensive wild-type mice. Therefore, in the absence of alpha-calcitonin gene-related peptide, deoxycorticosterone-salt hypertension induces enhanced oxidative stress, inflammation, and renal histopathologic damage, resulting in reduced renal function. Thus, sensory nerves, via alpha-calcitonin gene-related peptide, appear to be renoprotective against hypertension-induced damage. PMID:15928032

Bowers, Mark C; Katki, Khurshed A; Rao, Arundhati; Koehler, Michael; Patel, Parag; Spiekerman, Alvin; DiPette, Donald J; Supowit, Scott C

2005-05-31

78

A Novel Inhibitor of Inducible Nitric Oxide Synthase, ONO1714, Does Not Ameliorate Hypoxia-induced Pulmonary Hypertension in Rats  

Microsoft Academic Search

A recent study showed that long-term administration of the inducible nitric oxide synthase (iNOS) inhibitor L-NIL reduced\\u000a the development of pulmonary hypertension. The purpose of the present study was to identify the effect of an another iNOS\\u000a inhibitor, ONO-1714, on the development of pulmonary hypertensive vascular changes in chronic hypoxic pulmonary hypertension\\u000a in rats. ONO-1714 was administered to rats exposed

Bao Hua Jiang; Junko Maruyama; Ayumu Yokochi; Yoshihide Mitani; Kazuo Maruyama

2007-01-01

79

Cardiac weight in hypertension induced by nitric oxide synthase blockade.  

PubMed

Wistar rats given a nitric oxide synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME), for 4 weeks develop time- and dose-dependent hypertension without cardiac hypertrophy. This initial study of the relation between left ventricular weight and L-NAME-induced hypertension has now been extended by giving 50 mg/kg per day L-NAME to Wistar rats (n = 30) for 8 weeks and comparing results with those from control rats (n = 10) and two-kidney, one clip rats (n = 14). Although L-NAME rats and two-kidney, one clip rats had increased systolic blood pressures during the last 3 weeks of the experiment (202 +/- 24 and 224 +/- 16 mm Hg, respectively), the ratio of left ventricular weight to body weight of L-NAME rats (2.12 +/- 0.32 mg/g) was not statistically different from that of control rats (1.93 +/- 0.13 mg/g), whereas that of two-kidney, one clip rats was increased (2.85 +/- 0.20 mg/g). The plasma renin activity of L-NAME rats was not significantly different from that of control rats. Two L-NAME rat subgroups were defined according to the presence of left ventricular hypertrophy (ratio of left ventricular weight to body weight > 2.19 mg/g, control mean +2 SD) (6 of 25) or its absence (19 of 25). Systolic blood pressure, plasma renin activity, and cardiac angiotensin converting enzyme activity of L-NAME rats with left ventricular hypertrophy were significantly higher than those of the subgroup without.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8349331

Arnal, J F; el Amrani, A I; Chatellier, G; Ménard, J; Michel, J B

1993-09-01

80

Diabetes and Hypertension in Severe Obesity and Effects of Gastric Bypass-Induced Weight Loss  

PubMed Central

Objective To evaluate the preoperative relationships of hypertension and diabetes mellitus in severe obesity and the effects of gastric bypass (GBP)-induced weight loss. Summary Background Data Severe obesity is associated with multiple comorbidities, particularly hypertension and type 2 diabetes mellitus, that may affect life expectancy. Methods The database of patients who had undergone GBP by one general surgeon at a university hospital between September 1981 and January 2000 was queried as to weight, body mass index (BMI), pre- and postoperative diabetes, hypertension, and other comorbidities, including sleep apnea, hypoventilation, gastroesophageal reflux, degenerative joint disease, urinary incontinence, venous stasis, and pseudotumor cerebri. Results Of 1,025 patients treated, 15% had type 2 diabetes mellitus and 51% had hypertension. Of those with diabetes, 75% also had hypertension. There was a progressive increase in age between patients who had neither diabetes nor hypertension, either diabetes or hypertension, or both diabetes and hypertension. At 1 year after GBP (91% follow-up), patients lost 66 ± 18% excess weight (%EWL) or 35 ± 9% of their initial weight (%WL). Hypertension resolved in 69% and diabetes in 83%. Patients who resolved their hypertension or diabetes had greater %EWL and %WL than those who did not. African-American patients had a higher risk of hypertension than whites before GBP and were less likely to correct their hypertension after GBP. There was significant resolution of other obesity comorbidity problems. At 5 to 7 years after GBP (50% follow-up), %EWL was 59 ± 24 and %WL was 31 ± 13; resolution of hypertension was 66% and diabetes 86%. Conclusions These data suggest that type 2 diabetes mellitus and hypertension may be indirectly related to each other through the effects of obesity, but not directly as to cause and effect. The longer a person remains severely obese, the more likely he or she is to develop diabetes, hypertension, or both. GBP-induced weight loss is effective in correcting diabetes, hypertension, and other comorbidities but is related to the %EWL achieved. Severely obese African-Americans were more likely to have hypertension and respond less well to GBP surgery than whites. These data suggest that GBP surgery for severe obesity should be provided earlier to patients to prevent the development of diabetes and hypertension and their complications.

Sugerman, Harvey J.; Wolfe, Luke G.; Sica, Domenic A.; Clore, John N.

2003-01-01

81

[Cold-induced changes in blood lipoproteins in normotensive and hypertensive rats].  

PubMed

It is shown that in thermoneutral conditions ISIAH (Inherited Stress-Induced Arterial Hypertension) hypertensive rats had a lower level of high-density lipoproteins (HDLP) in plasma and a higher atherogenic coefficient compared to normotensive Wistar rats. After cooling there were different changes in fractional composition of plasma lipoproteins both in normo- and hypertensive rats. These changes depended on the cooling rate and were more pronounced after slow cooling. Slow cooling resulted in a more significant increase of plasma HDLP and in a greater decrease in LDLP and atherogenic coefficient in hypertensive rats compared to normotensive ones. PMID:16607890

Kozyreva, T V; Lomakina, S V; Tuzikov, F V; Tuzikova, N A

82

Drug-induced pulmonary arterial hypertension: a recent outbreak.  

PubMed

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

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

2013-09-01

83

A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension  

PubMed Central

Although glucocorticoid (GC)-induced hypertension has commonly been attributed to promiscuous activation of the mineralocorticoid receptor by cortisol, thereby promoting excess reabsorption of sodium and water, numerous lines of evidence indicate that this is not the only or perhaps even the primary mechanism. GC induce a number of effects on vascular smooth muscle (VSM) in vitro that may be pertinent to hypertension, but their contribution in vivo is unknown. To address this question, a mouse model with a tissue-specific knockout (KO) of the GC receptor in the VSM was created and characterized. Similar to control mice, KO mice exhibited normal baseline BP and, interestingly, showed normal circadian variation in BP. When dexamethasone was administered, however, the acute hypertensive response was markedly attenuated in KO mice, and there was a trend toward a decreased chronic hypertensive response. These data suggest that the GC receptor in VSM plays a critical role in the acute hypertensive response to GC in vivo.

Goodwin, Julie E.; Zhang, Junhui; Geller, David S.

2008-01-01

84

Renal and Adrenal Factors in Radiation-Induced Hypertension and Nephrosclerosis.  

National Technical Information Service (NTIS)

Experiments were conducted in order to investigate the effects of adrenalectomy on the incidence, severity, and rate of progression of radiation-induced hypertension and nephrosclerosis in male rats. Adrenalectomized and non-adrenalectomized rats received...

A. G. Lurie

1973-01-01

85

End-tidal carbon monoxide measurements in women with pregnancy-induced hypertension and preeclampsia  

Microsoft Academic Search

Objective: We sought to compare the end-tidal carbon monoxide breath levels in pregnant women with and without pregnancy-induced hypertension and preeclampsia. Study Design: We prospectively performed end-tidal carbon monoxide measurements corrected for ambient carbon monoxide in nonsmoking women during late gestation (>31 weeks). The study group included 22 women with pregnancy-induced hypertension or symptoms of preeclampsia and a control group

Micha Baum; Eyal Schiff; Doron Kreiser; Phyllis A. Dennery; David K. Stevenson; Thelma Rosenthal; Daniel S. Seidman

2000-01-01

86

Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension  

Microsoft Academic Search

Superoxide dismutase, catalase, glutathione peroxidase and NADPH oxidase in lead-induced hypertension.BackgroundEarlier studies from this laboratory have revealed the presence of oxidative stress and its role in the pathogenesis of lead-induced hypertension (HTN). We have further shown evidence of increased hydroxyl radical (·OH) and superoxide production in lead-treated rats and cultured endothelial cells. This study was designed to determine whether oxidative

Nosratola D Vaziri; Ching-Yi Lin; Farbod Farmand; Ram K Sindhu

2003-01-01

87

Safety of losartan in hypertensive patients with thiazide-induced hyperuricemia  

Microsoft Academic Search

Safety of losartan in hypertensive patients with thiazide-induced hyperuricemia.BackgroundLosartan, an angiotensin II receptor antagonist, has been shown to decrease serum uric acid and to increase urinary excretion of uric acid.MethodsTo determine if this effect can increase the risk of acute urate nephropathy, 63 hypertensive patients with thiazide-induced asymptomatic hyperuricemia (serum uric acid 7.0 to 12.0 mg\\/dl) were randomized double-blind to

Shahnaz Shahinfar; Roger L. Simpson; Alexandra D. Carides; Balasamy Thiyagarajan; Yasushi Nakagawa; Jason G. Umans; Joan H. Parks; Fredric L. Coe

1999-01-01

88

The portal hypertensive gastric mucosa: histologic, ultrastructural, and functional analysis after aspirin-induced damage.  

PubMed

We assessed macroscopic, histologic, ultrastructural, and functional features of aspirin-induced gastric mucosal injury in portal hypertensive and sham-operated rats. Portal hypertension was produced by staged portal vein ligation. Four hours after intragastric acidified aspirin administration, intraluminal pH in portal hypertensive rats was 6.6 +/- 0.2 and 4.3 +/- 0.5 in sham-operated controls (p less than 0.01). Gross mucosal damage was significantly greater in portal hypertensive rats compared with controls (18 +/- 2 versus 7 +/- 1% of total mucosal area). Histologic deep necrosis involved 22 +/- 2% of mucosal section lengths in portal hypertensive rats compared with 7 +/- 1% in sham-operated rats (p less than 0.01). In portal hypertensive rats, histologic and ultrastructural evaluation demonstrated capillary endothelial abnormalities, arterialization of submucosal veins, and markedly greater severity of microvascular damage than in sham-operated controls. Neutralized aspirin (pH, 7.0) did not produce any significant damage detectable grossly, histologically, or by transmission electron microscopy in portal hypertensive rats. We conclude that acid-dependent aspirin-induced gastric mucosal damage is significantly increased in portal hypertension. PMID:3388181

Sarfeh, I J; Tarnawski, A; Hajduczek, A; Stachura, J; Bui, H X; Krause, W J

1988-07-01

89

CYTOCHROME P450 1B1 CONTRIBUTES TO ANGIOTENSIN II-INDUCED HYPERTENSION AND ASSOCIATED PATHOPHYSIOLOGY  

PubMed Central

Hypertension is the leading cause of cardiovascular diseases, and angiotensin II is one of the major components of the mechanisms that contribute to the development of hypertension. However, the precise mechanisms for the development of hypertension are unknown. Our recent study that angiotensin II-induced vascular smooth muscle cell growth is dependent on cytochrome P450 1B1 led us to investigate its contribution to hypertension caused by this peptide. Angiotensin II was infused via miniosmotic pump into rats (150 ng/kg/min) or mice (1000 ?g/kg/day) for 13 days resulting in increased blood pressure, increased cardiac and vascular hypertrophy, increased vascular reactivity to vasoconstrictor agents, increased reactive oxygen species production, and endothelial dysfunction in both species. The increase in blood pressure and associated pathophysiological changes were minimized by the cytochrome P450 1B1 inhibitor, 2,3?,4,5?-tetramethoxystilbene in both species and was markedly reduced in Cyp1b1-/- mice. These data suggest that cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiological changes. Moreover, 2,3?,4,5?-tetramethoxystilbene which prevents both cytochrome P450 1B1-dependent and independent components of angiotensin II-induced hypertension and inhibits associated pathophysiological changes could be clinically useful in the treatment of hypertension and associated cardiovascular and inflammatory diseases.

Jennings, Brett L.; Sahan-Firat, Seyhan; Estes, Anne M.; Das, Kanak; Farjana, Nasreen; Fang, Xiao R.; Gonzalez, Frank J.; Malik, Kafait U.

2010-01-01

90

Apelin-induced hemorheological alterations in DOCA-salt hypertensive rats.  

PubMed

Apelin is a hypotensive peptide. Red blood cell (RBC) deformability and aggregation were previously demonstrated to be altered in various hypertension (HT) models. In the present study, we investigated possible alterations in RBC deformability and aggregation in response to apelin in DOCA-salt hypertensive rats. Rats were randomly divided into 4 groups: Control (C), Hypertension (HT), Apelin, and Apelin + Hypertension (Apelin + HT). HT was induced by injection of DOCA-salt (25 mg/kg, s.c.) twice weekly for 4 weeks, whereas apelin was administered (200 ?g/kg i.p.) for 17 days. RBC deformability and aggregation were determined using an ektacytometer. Blood pressure was monitored using a tail cuff system. Systolic blood pressure was decreased in the Apelin and Apelin + HT groups and increased in the HT group. RBC deformability was not significantly altered in the HT group. Apelin administration induced a statistically significant increase in RBC deformability in control animals, whereas erythrocytic deformability in the Apelin + HT group was decreased compared to the Apelin group. RBC aggregation of hypertensive animals was reduced compared to controls. Apelin administration induced increased RBC aggregation in hypertensive rats. Our results showed favorable effects of apelin on RBC deformability in control animals, but not in hypertensive rats. PMID:23302598

Kursunluoglu-Akcilar, Raziye; Kilic-Toprak, Emine; Kilic-Erkek, Ozgen; Turgut, Sebahat; Bor-Kucukatay, Melek

2013-01-01

91

Drug induced intracranial hypertension associated with sulphasalazine treatment.  

PubMed

A 25-year-old female patient developed headache and papilledema under sulphasalazine treatment for ulcerative colitis. The patient met the International Headache Society's criteria for idiopathic intracranial hypertension. Sulphasalazine was discontinued and the patient was given azathioprine for ulcerative colitis and acetazolamide for intracranial hypertension. Three weeks later, her examination was normal and lumbar puncture revealed an opening pressure of 180-mm H(2)O. Sulphasalazine is a product of 5 aminosalicylate (5 ASA) and there seems to be a relationship between the administration of sulphasalazine and the onset of intracranial hypertension symptoms. Early diagnosis of intracranial hypertension is important in patients with ulcerative colitis receiving 5 ASA treatment to prevent visual complications. PMID:18070060

Sevgi, Eser; Yalcin, Gul; Kansu, Tulay; Varli, Kubilay

2007-12-07

92

A dose response relation for noise induced hypertension.  

PubMed Central

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.

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

1991-01-01

93

Influence of hypertension on acetaldehyde-induced vasorelaxation in rat thoracic aorta.  

PubMed

Ethanol causes vasoconstriction and contributes to the development of hypertension. Acetaldehyde (ACA), the primary metabolite of ethanol, elevates blood pressure by releasing endogenous catecholamines. In vitro, ACA leads to vasorelaxation, although the response may vary among various vascular beds. This study examined the influence of hypertensive state on the ACA-induced vasorelaxant responsiveness. Ring segments of thoracic aorta were isolated from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) and isometric tension development was measured. In aorta with or without intact endothelium, the contractile responses to KCl and norepinephrine were greatly attenuated, whereas vasoconstrictive response to 5-HT was enhanced, by hypertension. Vasorelaxant response to histamine was similar between WKY and SHR groups. ACA (1-30 mM) elicited endothelium-intact as well as -denuded vasorelaxation in a dose-dependent manner in aorta from both WKY and SHR groups. Interestingly, the ACA-induced endothelium-intact vasorelaxation was significantly diminished, whereas the ACA-induced endothelium-denuded vasorelaxation was significantly augmented, by hypertension. These data indicated that the ACA-induced vasorelaxant response, either endothelium-intact or-denuded, is altered by the hypertensive state. PMID:11884215

Ren, Jun; Wang, Guei-Jane; Petrovski, Pauline; Ren, Bonnie H; Brown, Ricardo A

2002-03-01

94

The contribution of nitric oxide to renal vascular wall thickening in rats with l -NAME-induced hypertension  

Microsoft Academic Search

We investigated the mechanisms of renal vascular wall thickening in a rat model of N-nitro L-arginine methyl ester (L-NAME)-induced hypertension. To separate the effects of L-NAME-induced hypertension from other effects\\u000a of nitric oxide (NO) inhibition, we created two models of L-NAME-induced hypertension: both had the same blood pressure level\\u000a but NO inhibition was moderate in one group (group M) and

T. Yoneyama; Sakae Ohkawa; Tomoko Watanabe; Mari Odamaki; Hiromichi Kumagai; Masato Kimura; Akira Hishida

1998-01-01

95

Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction  

Microsoft Academic Search

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension\\u000a and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant\\u000a in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial\\u000a Nox2 in vivo. To address this question,

Colin E. Murdoch; Sara P. Alom-Ruiz; Minshu Wang; Min Zhang; Simon Walker; Bin Yu; Alison Brewer; Ajay M. Shah

2011-01-01

96

New developments in mechanisms of obesity-induced hypertension: Role of adipose tissue  

Microsoft Academic Search

Hypertension develops in almost 60% of obese individuals. Apart from the recent observation of obesity-associated structural\\u000a changes in kidney structure that may lead to enhanced tubular sodium reabsorbtion, reports of paracrine and hormonal factors\\u000a derived from adipose tissue have prompted speculations about the role of adipose tissue in the pathophysiology of obesity-induced\\u000a hypertension. We summarize recent data on leptin’ sympathoexcitatory

Arya M. Sharma; Stefan Engeli; Tobias Pischon

2001-01-01

97

Chronic Hypertension Aggravates Heat Stress-Induced Brain Damage: Possible Neuroprotection by Cerebrolysin  

Microsoft Academic Search

\\u000a Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with\\u000a normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and\\u000a brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38°C in a biological oxygen demand (BOD)\\u000a incubator showed breakdown of the blood–brain

Dafin Fior Muresanu; Sibilla Zimmermann-Meinzingen; Hari Shanker Sharma

98

Focal Cerebral Ischemia in Rats: Effects of Induced Hypertension, During Reperfusion, on CBF  

Microsoft Academic Search

Summary: The effect of phenylephrine-induced hypertension on CBF was investigated after 120 min of middle cerebral artery occlusion in rats. Blood pressure was manipulated by one of the following schedules during a 90-min period of reperfusion: 90\\/NORM, 90 min of nor-motensive reperfusion; 90\\/HTN, 90 min of hypertensive reperfusion (MABP increased by 30 mm Hg); or 15\\/HTN, the 90-min period of

Daniel J. Cole; Jerry S. Matsumura; John C. Drummond; Randall M. Schell

1992-01-01

99

Myocardial infarction in a young female with reninoma induced hypertension and myocardial bridging  

Microsoft Academic Search

We present a case of myocardial infarction in a young female with reninoma induced hypertension and myocardial bridging. Reninoma\\u000a is a rare and curable cause of secondary hypertension. Currently developed multi-detector computed tomography (MDCT) has permitted\\u000a better evaluation of myocardial infarction and myocardial bridging. Myocardial infarction associated with reninoma and myocardial\\u000a bridging has not been reported, and we report this

Bae Young Lee; Kyung Sup Song; Eun Joo Seo; Eun Ju Cho; Su Yeon Cho

2007-01-01

100

Enhanced development of azoxymethane-induced colonic preneoplastic lesions in hypertensive rats.  

PubMed

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

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

2013-07-15

101

Propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats.  

PubMed

In a standardized rat model of portal hypertension, we investigated the effects of propranolol on alcohol-induced gastric mucosal damage. Portal hypertensive rats pretreated with 2 mg propranolol, compared with those receiving saline, had significantly reduced portal pressures (24 +/- 1 vs 32 +/- 1 cm saline), macroscopic mucosal damage (24 +/- 1 vs 39 +/- 4% of mucosa), and histologic deep necrosis (36 +/- 2 vs 61 +/- 4% of mucosal length). Increased dosage of propranolol to 4 mg did not produce any further reduction of portal pressure or mucosal damage. Central venous and systemic arterial pressures were not significantly altered by propranolol. The extent of mucosal damage correlated with levels of portal pressure (P less than 0.01) in portal hypertensive rats. Sham-operated normotensive rats had less macroscopic mucosal damage (26 +/- 4%) than portal hypertensive rats, and propranolol did not affect the extent of ethanol-induced damage or portal pressures in these animals. We conclude: (1) Propranolol is effective in reducing extent of ethanol-induced gastric mucosal damage in portal hypertensive rats, but not in sham-operated controls; (2) this effect correlates with reduction of portal pressure; and (3) our study supports the clinical impression that reducing portal pressure may be one approach for the prevention and therapy of gastric mucosal damage in portal hypertension. PMID:3943443

Sankary, H; Sarfeh, I J; Tarnawski, A; Maeda, R; Ivey, K J; Mason, G R

1986-02-01

102

Hypertensive crisis-induced electrocardiographic changes: a case series  

Microsoft Academic Search

INTRODUCTION: Myocardial injury is one of the most notorious complications of a hypertensive crisis. Key electrocardiograph signs used to detect cardiac injury such as ST segment changes and cardiac arrhythmias usually indicate acute ongoing end-organ damage. Lack of early signs to predict end-organ damage might lead to a delay in the initiation of therapy and selection of the incorrect therapeutic

Khalid Abou Farha; André van Vliet; Sjoerd van Marle; Patrick Vrijlandt; Daan Westenbrink

2009-01-01

103

Hypothalamic angiotensinergic–noradrenergic systems interaction in fructose induced hypertension  

Microsoft Academic Search

ObjectiveSeveral studies suggest the importance of the interaction between the renin angiotensin and sympathetic nervous systems in blood pressure control, especially in clinical situations such as the metabolic syndrome. Previously, we have demonstrated changes in noradrenergic hypothalamic control of blood pressure in an animal model of insulin resistance and hypertension. The aim of the present study was to evaluate the

Marcos A. Mayer; Christian Höcht; Mariela Gironacci; Javier A. W. Opezzo; Carlos A. Taira; Belisario E. Fernández; Ana M. Puyó

2008-01-01

104

CaMK4 Gene Deletion Induces Hypertension  

PubMed Central

Background The expression of calcium/calmodulin-dependent kinase IV (CaMKIV) was hitherto thought to be confined to the nervous system. However, a recent genome-wide analysis indicated an association between hypertension and a single-nucleotide polymorphism (rs10491334) of the human CaMKIV gene (CaMK4), which suggests a role for this kinase in the regulation of vascular tone. Methods and Results To directly assess the role of CaMKIV in hypertension, we characterized the cardiovascular phenotype of CaMK4?/? mice. They displayed a typical hypertensive phenotype, including high blood pressure levels, cardiac hypertrophy, vascular and kidney damage, and reduced tolerance to chronic ischemia and myocardial infarction compared with wild-type littermates. Interestingly, in vitro experiments showed the ability of this kinase to activate endothelial nitric oxide synthase. Eventually, in a population study, we found that the rs10491334 variant associates with a reduction in the expression levels of CaMKIV in lymphocytes from hypertensive patients. Conclusions Taken together, our results provide evidence that CaMKIV plays a pivotal role in blood pressure regulation through the control of endothelial nitric oxide synthase activity. (J Am Heart Assoc. 2012;1:e001081 doi: 10.1161/JAHA.112.001081.)

Santulli, Gaetano; Cipolletta, Ersilia; Sorriento, Daniela; Del Giudice, Carmine; Anastasio, Antonio; Monaco, Sara; Maione, Angela Serena; Condorelli, Gianluigi; Puca, Annibale; Trimarco, Bruno; Illario, Maddalena; Iaccarino, Guido

2012-01-01

105

Protein kinase G-I deficiency induces pulmonary hypertension through Rho A/Rho kinase activation.  

PubMed

Protein kinase G (PKG) plays an important role in the regulation of vascular smooth cell contractility and is a critical mediator of nitric oxide signaling, which regulates cardiovascular homeostasis. PKG-I-knockout (Prkg1(-/-)) mice exhibit impaired nitric oxide/cGMP-dependent vasorelaxation and systemic hypertension. However, it remains unknown whether PKG-I deficiency induces pulmonary hypertension. In this study, we characterized the hypertensive pulmonary phenotypes in Prkg1(-/-) mice and delineated the underlying molecular basis. We observed a significant increase in right ventricular systolic pressure in Prkg1(-/-) mice in the absence of systemic hypertension and left-sided heart dysfunction. In addition, we observed marked muscularization of distal pulmonary vessels in Prkg1(-/-) mice. Microangiography revealed impaired integrity of the pulmonary vasculature in Prkg1(-/-) mice. Mechanistically, PKG-I-mediated phosphorylation of Rho A Ser188 was markedly decreased, and the resultant Rho A activation was significantly increased in Prkg1(-/-) lung tissues, which resulted in Rho kinase activation. The i.t. administration of fasudil, a Rho kinase inhibitor, reversed the hypertensive pulmonary phenotype in Prkg1(-/-) mice. Taken together, these data show that PKG-I deficiency induces pulmonary hypertension through Rho A/Rho kinase activation-mediated vasoconstriction and pulmonary vascular remodeling. PMID:22632818

Zhao, Yidan D; Cai, Lei; Mirza, Muhammad K; Huang, Xiaojia; Geenen, Dave L; Hofmann, Franz; Yuan, Jason X-J; Zhao, You-Yang

2012-06-01

106

Atorvastatin prevented and partially reversed adrenocorticotropic hormone-induced hypertension in the rat.  

PubMed

1. Adrenocorticotropic hormone (ACTH)-induced hypertension is associated with nitric oxide (NO) deficiency and increased oxidative stress. Atorvastatin (Ato), an HMG-Co-enzyme-A reductase inhibitor has been reported to enhance availability of NO. The aim of the study was to assess whether pretreatment with Ato would prevent the development of ACTH-induced hypertension and whether established ACTH-induced hypertension could be reversed with subsequent administration of Ato in rats. 2. Male Sprague-Dawley rats (n = 60) were treated with Ato (30 mg/kg per day in drinking water) or tap water for 15 days. ACTH (0.2 mg/kg per day s.c) or saline was started 4 days after Ato treatment or non-treated rats and continued for 11-13 days (prevention study). In the reversal study, Ato was given on day 8 of ACTH/Saline treatment for 5 days. Systolic blood pressure (SBP) was measured on alternate days using the tail cuff method. 3. Adrenocorticotropic hormone treatment increased SBP (110 +/- 2-136 +/- 2 mmHg, P < 0.001) and aortic superoxide production (P < 0.001). Ato alone did not alter SBP, but Ato pretreatment prevented ACTH-induced hypertension compared with that in rats treated with ACTH alone (118 +/- 2 and 136 +/- 2 mmHg, respectively, P cent < 0.01). Ato partially reversed ACTH-induced hypertension (124 +/- 3 and 136 +/- 2 mmHg, respectively, P cent < 0.05). Plasma nitrate/nitrite (NOx) was decreased in ACTH-treated rats compared with saline treated rats (6.6 +/- 0.4 saline and 4.5 +/- 0.5 micromol/L ACTH, P < 0.001). Atorvastatin affected neither plasma NOx nor aortic superoxide production. 4. Atorvastatin prevented and partially reversed ACTH-induced hypertension in the rat. PMID:16620303

Mondo, Charles K; Yang, Wan-Song; Su, Ji-Zhou; Huang, Ti-Gang

2006-04-01

107

Propylene-Glycol-Induced Pulmonary Hypertension in Sheep  

Microsoft Academic Search

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

Ronald G. Pearl; Susan A. Rice

1989-01-01

108

Ketanserin in the treatment of protamine-induced pulmonary hypertension.  

PubMed Central

The reversal of heparin by protamine may cause severe hemodynamic deterioration, characterized by systemic hypotension, pulmonary hypertension, and bronchoconstriction. A case report is presented concerning the administration of ketanserin in the treatment of pulmonary vasoconstriction and right ventricular failure following the infusion of protamine in a patient undergoing coronary artery bypass surgery and mitral valve replacement. The potential role of serotonin in the development of this serious complication is discussed.

van der Starre, P J; Solinas, C

1996-01-01

109

Nonuniformity of CBF response to NE- or ANG II-induced hypertension in rabbits.  

PubMed

The regional response of brain vasculature to moderate hypertension was investigated using two hypertensive drugs, norepinephrine (NE) and angiotensin II (ANG II), infused intravenously at low concentrations (increase in blood pressure 15-40 mm Hg). Regional cerebral blood flow (rCBF) was measured in unanesthetized and anesthetized rabbits using the [14C]ethanol saturation technique. In both groups of animals, NE and ANG II induced regional differences in the flow changes as compared with controls, confirming a regional (or segmental) heterogeneity in the regulatory mechanisms to hypertension. The responses to identical rises in blood pressure (BP) in most of the structures analyzed depended on the drug used. In the unanesthetized rabbits, the increase in vascular resistance induced by NE was greater than that induced by ANG II. With the two drugs, there was no correlation between the flow changes in any of the structures considered and either the BP increase or the BP level in unanesthetized animals. However, these flow changes were correlated with the BP increase in anesthetized animals, although differences between the effects of NE and ANG II were again observed. This study suggests that cerebrovascular regulatory mechanisms in hypertension are probably more complex than a simple myogenic reaction. Their heterogeneity and their dependence both on the cause of hypertension and on the presence of anesthetics suggest the intervention of an integrating pathway. PMID:3605371

Reynier-Rebuffel, A M; Aubineau, P; Issertial, O; Seylaz, J

1987-07-01

110

Insulin resistance-induced hypertension and a role of perivascular CGRPergic nerves.  

PubMed

Insulin resistance is defined as a preliminary step of type 2 diabetes mellitus with decreased insulin action evoked by continuous postprandial hyperglycemia, which is provoked by high fat and calories dieting, a lack of physical activity and obesity. In the early phase of type 2 diabetes mellitus, patients have a hyperinsulinemia to compensate deficient insulin action by increased secretion from the pancreas to maintain euglycemia. Then, pancreatic ? cells progressively decrease secretion function, resulting in the development of diabetes mellitus with decreased serum insulin levels. Accumulating evidences show that insulin resistance is associated with hypertension. However, the mechanisms underlying hypertension associated with type 2 diabetes mellitus have still unknown. Therefore, to elucidate the mechanisms of insulin resistance-induced hypertension, we investigated that the effects of hyperinsulinemia or hyperglycemia on vascular responses mediated by perivascular nerves including sympathetic adrenergic nerves and calcitonin gene-related peptide (CGRP)-containing nerves (CGRPergic nerves). In this article, we show evidence that insulin resistance-induced hypertension could be resulted from increased density and function of sympathetic nerve, and decreased density and function of CGRPergic nerves. Furthermore, our findings provide a new insight into the research of therapeutic drugs for insulin resistance-induced hypertension. PMID:23745744

Takatori, Shingo; Zamami, Yoshito; Hashikawa-Hobara, Narumi; Kawasaki, Hiromu

2013-06-01

111

Vascular Endothelial Growth Factor Inhibitor-Induced Hypertension: Basics for Primary Care Providers  

PubMed Central

Frequently, primary care providers continue to manage the overall medical care of cancer patients. With newer and often more potent antitumor agents, patients may present to their local physicians with drug-induced toxicities such as hypertension induced by vascular endothelial growth factor (VEGF) inhibitors. It is imperative that these healthcare providers are aware of basic aspects of this drug class, as its use has increased significantly in the last several years. Uncontrolled or malignant hypertension due to these agents should be recognized readily and treated early to prevent more severe outcomes. This overview provides a brief background on the role of VEGF and angiogenesis in tumor metabolism as well as theories of the mechanism of VEGF inhibitors and hypertension. Helpful clinical practice aspects including the types of inhibitors used in the United States and their pharmacologic characteristics will be discussed. Also, diagnosis and treatment of hypertension induced by vascular endothelial growth factors are reviewed. A summary of key aspects of this drug class and hypertension is included.

Escalante, Carmen P.; Zalpour, Ali

2011-01-01

112

Influence of non-pharmacological treatment (contemplative meditation and breathing technique) on stress induced hypertension- a randomized controlled study  

Microsoft Academic Search

Background: Stress induced hypertension is a very common disorder in the industrialized world. Medication alone is often inadequate to effectively control high blood pressure. Non-pharmacological antihypertensive interventions in arterial hypertension are weakly characterized. We investigated the effect of contemplative meditation combined with breathing techniques (CMBT) on stress and exercise induced high blood pressure (BP). CMBT was performed according to the

Paul Manikonda; Stefan Stoerk; Simone Toegel; Fritz Schardt; Christiane Angermann; Isaak Gruenberger; Ottmar Fuchs; Hermann Faller; Wolfram Voelker

2005-01-01

113

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

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

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

2011-01-01

114

Bile acid-induced gastric mucosal injury: significance of portal hypertension and mucosal capillary permeability.  

PubMed

Rats with portal vein occlusion (PVO) were studied to determine severity of taurocholate-induced gastric mucosal injury during portal hypertension and following its resolution by collaterals. During the portal hypertensive state, after intragastric taurocholate, PVO rats compared with sham-operated controls had significantly greater macroscopic damage (14 +/- 1 vs 3 +/- 1% of total mucosa) and histologic deep necrosis (25 +/- 4 vs 3 +/- 1% of mucosal length). Gastric mucosal capillary permeability was also significantly greater in PVO rats, as assessed by increased appearance of intravenous Evans blue dye in gastric wall and contents. After 21 days of PVO portal pressures returned to normal. At this time taurocholate-induced gastric mucosal damage and capillary leak became similar in PVO and sham-operated rats. It is concluded that the portal hypertensive state alone predisposes to severe gastric mucosal damage and capillary leak. PMID:6708496

Maeda, R; Guilmette, E; Tarnawski, A; Sarfeh, I J

1984-04-01

115

Resolution of pulmonary hypertension complication during venovenous perfusion-induced systemic hyperthermia application.  

PubMed

We are developing a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced cancer treatment. The vv-PISH system consistently delivered hyperthermia to adult healthy swine, but significant pulmonary hypertension developed during the heating phase. The goal of this study was to develop a method to prevent pulmonary hypertension. We hypothesized that pulmonary hypertension results from decreased priming solution air solubility, which causes pulmonary gas embolism. Healthy adult sheep (n = 3) were used to establish a standard vv-PISH sheep model without priming solution preheating. In subsequent sheep (n = 7), the priming solution was preheated (42-46°C) and the hyperthermia circuit flushed with CO2. All sheep survived the experiment and achieved 2 hours of 42°C hyperthermia. In the group lacking priming solution preheating, significant pulmonary hypertension (35-44 mm?Hg) developed. In the sheep with priming solution preheating, pulmonary artery pressure was very stable without pulmonary hypertension. Blood electrolytes were in physiologic range, and complete blood counts were unaffected by hyperthermia. Blood chemistries revealed no significant liver or kidney damage. Our simple strategy of priming solution preheating completely resolved the problem of pulmonary hypertension as a milestone toward developing a safe and easy-to-use vv-PISH system for cancer treatment. PMID:23820278

Ballard-Croft, Cherry; Wang, Dongfang; Jones, Cameron; Wang, Jingkun; Pollock, Robert; Jubak, Bob; Topaz, Stephen; Zwischenberger, Joseph B

116

Rosiglitazone attenuates chronic hypoxia-induced pulmonary hypertension in a mouse model.  

PubMed

Chronic hypoxia contributes to pulmonary hypertension through complex mechanisms that include enhanced NADPH oxidase expression and reactive oxygen species (ROS) generation in the lung. Stimulation of peroxisome proliferator-activated receptor gamma (PPARgamma) reduces the expression and activity of NADPH oxidase. Therefore, we hypothesized that activating PPARgamma with rosiglitazone would attenuate chronic hypoxia-induced pulmonary hypertension, in part, through suppressing NADPH oxidase-derived ROS that stimulate proliferative signaling pathways. Male C57Bl/6 mice were exposed to chronic hypoxia (CH, Fi(O2) 10%) or room air for 3 or 5 weeks. During the last 10 days of exposure, each animal was treated daily by gavage with either the PPARgamma ligand, rosiglitazone (10 mg/kg/d) or with an equal volume of vehicle. CH increased: (1) right ventricular systolic pressure (RVSP), (2) right ventricle weight, (3) thickness of the walls of small pulmonary vessels, (4) superoxide production and Nox4 expression in the lung, and (5) platelet-derived growth factor receptor beta (PDGFRbeta) expression and activity and reduced phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression. Treatment with rosiglitazone prevented the development of pulmonary hypertension at 3 weeks; reversed established pulmonary hypertension at 5 weeks; and attenuated CH-stimulated Nox4 expression and superoxide production, PDGFRbeta activation, and reductions in PTEN expression. Rosiglitazone also attenuated hypoxia-induced increases in Nox4 expression in pulmonary endothelial cells in vitro despite hypoxia-induced reductions in PPARgamma expression. Collectively, these findings indicate that PPARgamma ligands attenuated hypoxia-induced pulmonary vascular remodeling and hypertension by suppressing oxidative and proliferative signals providing novel insights for mechanisms underlying therapeutic effects of PPARgamma activation in pulmonary hypertension. PMID:19520921

Nisbet, Rachel E; Bland, Jennifer M; Kleinhenz, Dean J; Mitchell, Patrick O; Walp, Erik R; Sutliff, Roy L; Hart, C Michael

2009-06-11

117

ACE2 overexpression in the paraventricular nucleus attenuates angiotensin II-induced hypertension  

PubMed Central

Aims Angiotensin II (Ang II) has been shown to have both central and peripheral effects in mediating hypertension, for which the hypothalamic paraventricular nucleus (PVN) is an important brain cardio-regulatory centre. Angiotensin-converting enzyme 2 (ACE2) has been identified as a negative regulator of the pro-hypertensive actions of Ang II. Recent findings from our laboratory suggest that Ang II infusion decreases ACE2 expression in the PVN. In the present study, we hypothesized that ACE2 overexpression in the PVN will have beneficial effects in counteracting Ang II-induced hypertension. Methods and results Male Sprague-Dawley rats were used in this study. Bilateral microinjection of an adenovirus encoding hACE2 (Ad-ACE2) into the PVN was used to overexpress ACE2 within this region. Mean arterial pressure measured by radiotelemetry was significantly increased after 14 days in Ang II-infused (200 ng/kg/min) rats vs. saline-infused controls (162.9 ± 3.6 vs. 102.3 ± 1.5 mmHg). Bilateral PVN microinjection of Ad-ACE2 attenuated this Ang II-induced hypertension (130.2 ± 5.7 vs. 162.9 ± 3.6 mmHg). ACE2 overexpression also significantly decreased AT1R and ACE expression and increased AT2R and Mas expression in the PVN. Additionally, ACE2 overexpression in the PVN attenuated the Ang II-induced increase in the expression of the pro-inflammatory cytokines tumour necrosis factor-?, interleukin (IL)-1? and IL-6 in the PVN. Conclusion Our findings suggest that attenuation of pro-inflammatory cytokines in the PVN in combination with the shift of the renin–angiotensin system towards the anti-hypertensive axis (ACE2/Ang-(1–7)/Mas) may be responsible for the overall beneficial effects of ACE2 overexpression in the PVN on the Ang II-induced hypertensive response.

Sriramula, Srinivas; Cardinale, Jeffrey P.; Lazartigues, Eric; Francis, Joseph

2011-01-01

118

Sex chromosome effects unmasked in angiotensin II-induced hypertension  

PubMed Central

Sex differences in mean arterial pressure (MAP) are reported in many experimental models of hypertension and are ascribed to gonadal sex based of studies showing gonadectomy and gonadal hormone replacement affect MAP. The interpretation of these studies, however, has been confounded by differences in the sex chromosome complement (XX vs. XY). To investigate the sex chromosome complement independently of gonadal sex, we used the four core genotype (FCG) mouse model in which gonadal sex is separated from the sex chromosome complement enabling comparisons among XX and XY females and XX and XY males. We found that in the gonadectomized (GDX) FCG, MAP after 2 weeks of angiotensin II (Ang II) infusion (200 ng/kg/min) was greater in XX than XY [MAP (mm Hg): GDX-XX-Female, 148±4.5; GDX-XY-Female, 133±4.4; GDX-XX-Male, 149±9.4; GDX-XY-Male, 138±5.5; p<0.03, XX vs XY; n=8-9/grp]. In contrast, no sex chromosome effects (SCE) were found on heart rate (HR) body weight (BW) or plasma Ang II 2 weeks after Ang II infusion. This study suggests that in addition to effects of gonadal hormones on blood pressure, X- or Y-linked genes, parental imprinting or X mosaicism contribute to sex differences in hypertension. Furthermore, the finding that MAP was greater in XX mice compared to XY mice in the GDX state suggests adverse SCE encoded within the XX sex chromosome complement could contribute to hypertension in women with ovarian hormone deficiency such as postmenopausal women and women with premature ovarian failure.

Ji, Hong; Zheng, Wei; Wu, Xie; Liu, Jun; Ecelbarger, Carolyn M.; Watkins, Rebecca; Arnold, Arthur P.; Sandberg, Kathryn

2010-01-01

119

Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension  

PubMed Central

Background Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension in rats. Methods Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from day 21 to 35 either with TBC3711 (Dose: 30 mg/kg body weight/day) or placebo. Echocardiographic measurements of different hemodynamic and right-heart hypertrophy parameters were performed. After day 35, rats were sacrificed for invasive hemodynamic and right-heart hypertrophy measurements. Additionally, histologic assessment of pulmonary vascular and right-heart remodelling was performed. Results The novel endothelin-A receptor antagonist TBC3711 significantly attenuated monocrotaline-induced pulmonary hypertension, as evident from improved hemodynamics and right-heart hypertrophy in comparison with placebo group. In addition, muscularization and medial wall thickness of distal pulmonary vessels were ameliorated. The histologic evaluation of the right ventricle showed a significant reduction in fibrosis and cardiomyocyte size, suggesting an improvement in right-heart remodelling. Conclusion The results of this study suggest that the selective endothelin-A receptor antagonist TBC3711 demonstrates therapeutic benefit in rats with established pulmonary hypertension, thus representing a useful therapeutic approach for treatment of pulmonary hypertension.

2011-01-01

120

Chronic hypertension aggravates heat stress-induced brain damage: possible neuroprotection by cerebrolysin.  

PubMed

Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees C in a biological oxygen demand (BOD) incubator showed breakdown of the blood-brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier. PMID:19812973

Muresanu, Dafin Fior; Zimmermann-Meinzingen, Sibilla; Sharma, Hari Shanker

2010-01-01

121

Pharmacological Validation of a Feline Model of Steroid-Induced Ocular Hypertension  

Microsoft Academic Search

Objective: To validate pharmacologically the feline model of steroid-induced ocular hypertension. Methods: Serial studies were conducted in domesti- cated adult female cats trained to accept topical ocular drug administration and pneumotonometry. To estab- lish intraocular pressure (IOP) values for each study, mea- surements were performed at the same time of day for 6 consecutive days. Beginning on day 7, cats

Parimal Bhattacherjee; Christopher A. Paterson; Joan M. Spellman; G. Graff; John M. Yanni

122

Excess PTH in CRF induces pulmonary calcification, pulmonary hypertension and right ventricular hypertrophy  

Microsoft Academic Search

Excess PTH in CRF induces pulmonary calcification, pulmonary hypertension and right ventricular hypertrophy. Calcification of the lungs occurs in chronic renal failure (CRF) and may adversely affect both pulmonary and right ventricular function. The present study examined the role of excess parathyroid hormone (PTH) in the genesis of pulmonary calcifications in dogs with experimental CRF and evaluated calcium content of

Mohammad Akmal; Robert R Barndt; Azizullah N Ansari; John G Mohler; Shaul G Massry

1995-01-01

123

Overfeeding-Induced Obesity in Spontaneously Hypertensive Rats: An Animal Model of the Human Metabolic Syndrome  

Microsoft Academic Search

Background\\/Aims: The metabolic syndrome (MS) has become an epidemiological problem in Western countries. We developed a diet-induced obese rat model that mimics all the symptoms of MS in humans, but whose insulin resistance, hyperphagia and hyperleptinemia are caused by nutrition rather than genetic modifications. Methods: Spontaneously hypertensive rats (SHR) were allowed for 12 weeks to choose between a cafeteria diet

Anja Miesel; Helge Müller; Margot Thermann; Marc Heidbreder; Peter Dominiak; Walter Raasch

2010-01-01

124

Evaluation of the Myocilin (MYOC) Glaucoma Gene in Monkey and Human Steroid-Induced Ocular Hypertension  

Microsoft Academic Search

PURPOSE. Glucocorticoid-induced ocular hypertension (the ste- roid response) may result in optic nerve damage that very closely mimics the pathologic course of primary open angle glaucoma (POAG). In addition, patients with glaucoma and their relatives are much more likely to exhibit the steroid response than unaffected individuals, suggesting a potential link between the steroid response and POAG. Recently, the expression

John H. Fingert; Abbot F. Clark; Jamie E. Craig; Wallace L. M. Alward; Grant R. Snibson; Marsha McLaughlin; Linda Tuttle; David A. Mackey; Val C. Sheffield; Edwin M. Stone

2001-01-01

125

Body fluid volumes in rats with mestranol-induced hypertension  

SciTech Connect

Because estrogens have been reported to produce sodium retention, this study investigated the possibility that hypertension in rats resulting from the ingestion of an estrogen used as an oral contraceptive could be due to increases in body fluid volumes. Female rats were given feed containing mestranol for 1, 3, and 6 mo; control rats were given the feed without mestranol. The mestranol-treated rats had higher arterial pressures than the controls only after 6 mo of treatment. Plasma volume, extracellular fluid volume, and total body water were measured in each rat by the distribution volumes of radioiodinated serum albumin, /sup 32/SO/sub 4/, and tritiated water, respectively. The body fluid volumes, expressed per 100 g of body weight, were not different between the mestranol-treated rats and their controls at any of the three treatment times. Due to differences in body weight and lean body mass between the mestranol-treated and the control rats, these volumes also were expressed per 100 g of lean body mass. Again, no differences were observed between the mestranol-treated rats and the control rats for any of these body fluid compartments at any of the treatment times. These studies, therefore, were unable to provide evidence that increases in body fluid volumes contributed to the elevated arterial pressure in this rat model of oral contraceptive hypertension.

Fowler, W.L. Jr.; Johnson, J.A.; Kurz, K.D.; Zeigler, D.W.; Dostal, D.E.; Payne, C.G.

1986-07-01

126

The role of NADPH oxidase in chronic intermittent hypoxia-induced pulmonary hypertension in mice.  

PubMed

Obstructive sleep apnea, characterized by intermittent periods of hypoxemia, is an independent risk factor for the development of pulmonary hypertension. However, the exact mechanisms of this disorder remain to be defined. Enhanced NADPH oxidase expression and superoxide (O2(-).) generation in the pulmonary vasculature play a critical role in hypoxia-induced pulmonary hypertension. Therefore, the current study explores the hypothesis that chronic intermittent hypoxia (CIH) causes pulmonary hypertension, in part, by increasing NADPH oxidase-derived reactive oxygen species (ROS) that contribute to pulmonary vascular remodeling and hypertension. To test this hypothesis, male C57Bl/6 mice and gp91phox knockout mice were exposed to CIH for 8 hours per day, 5 days per week for 8 weeks. CIH mice were placed in a chamber where the oxygen concentration was cycled between 21% and 10% O2 45 times per hour. Exposure to CIH for 8 weeks increased right ventricular systolic pressure (RVSP), right ventricle (RV):left ventricle (LV) + septum (S) weight ratio, an index of RV hypertrophy, and thickness of the right ventricular anterior wall as measured by echocardiography. CIH exposure also caused pulmonary vascular remodeling as demonstrated by increased muscularization of the distal pulmonary vasculature. CIH-induced pulmonary hypertension was associated with increased lung levels of the NADPH oxidase subunits, Nox4 and p22phox, as well as increased activity of platelet-derived growth factor receptor beta and its associated downstream effector, Akt kinase. These CIH-induced derangements were attenuated in similarly treated gp91phox knockout mice. These findings demonstrate that NADPH oxidase-derived ROS contribute to the development of pulmonary vascular remodeling and hypertension caused by CIH. PMID:18952568

Nisbet, Rachel E; Graves, Anitra S; Kleinhenz, Dean J; Rupnow, Heidi L; Reed, Alana L; Fan, Tai-Hwang M; Mitchell, Patrick O; Sutliff, Roy L; Hart, C Michael

2008-10-23

127

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

PubMed

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

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

2004-12-06

128

The cerebrovascular dysfunction induced by slow pressor doses of angiotensin II precedes the development of hypertension.  

PubMed

Hypertension alters cerebrovascular regulation and increases the brain's susceptibility to stroke and dementia. We investigated the temporal relationships between the arterial pressure (AP) elevation induced by "slow pressor" angiotensin II (ANG II) infusion, which recapitulates key features of human hypertension, and the resulting cerebrovascular dysfunction. Minipumps delivering saline or ANG II for 14 days were implanted subcutaneously in C57BL/6 mice (n = 5/group). Cerebral blood flow was assessed by laser-Doppler flowmetry in anesthetized mice equipped with a cranial window. With ANG II (600 ng · kg(-1) · min(-1)), AP started to rise after 9 days (P < 0.05 vs. saline), remained elevated at 11-17 days, and returned to baseline at 21 days (P > 0.05). ANG II attenuated the cerebral blood flow increase induced by neural activity (whisker stimulation) or endothelium-dependent vasodilators, an effect observed before the AP elevation (7 days), as well as after the hypertension subsided (21 days). Nonpressor doses of ANG II (200 ng · kg(-1) · min(-1)) induced cerebrovascular dysfunction and oxidative stress without elevating AP (P > 0.05 vs. saline), whereas phenylephrine elevated AP without inducing cerebrovascular effects. ANG II (600 ng · kg(-1) · min(-1)) augmented neocortical reactive oxygen species (ROS) with a time course similar to that of the cerebrovascular dysfunction. Neocortical application of the ROS scavenger manganic(I-II)meso-tetrakis(4-benzoic acid)porphyrin or the NADPH oxidase peptide inhibitor gp91ds-tat attenuated ROS and cerebrovascular dysfunction. We conclude that the alterations in neurovascular regulation induced by slow pressor ANG II develop before hypertension and persist beyond AP normalization but are not permanent. The findings unveil a striking susceptibility of cerebrovascular function to the deleterious effects of ANG II and raise the possibility that cerebrovascular dysregulation precedes the elevation in AP also in patients with ANG II-dependent hypertension. PMID:20971763

Capone, Carmen; Faraco, Giuseppe; Park, Laibaik; Cao, Xian; Davisson, Robin L; Iadecola, Costantino

2010-10-22

129

Associations of Early Pregnancy Sleep Duration with Trimester-Specific Blood Pressures and Hypertensive Disorders in Pregnancy  

PubMed Central

Study Objectives: We evaluated the influence of maternal self-reported habitual sleep duration during early pregnancy on blood pressure (BP) levels and risk of hypertensive disorders of pregnancy. Design: Prospective cohort study. Setting: Clinic-based study. Participants: A cohort of 1,272 healthy, pregnant women. Measurements and Results: We abstracted maternal antenatal BP values from medical records and estimated mean BP differences across hours of sleep categories in regression models, using generalized estimating equations. Odds ratios (OR) and 95% confidence intervals (95% CIs) for pregnancy induced hypertension (PIH) and preeclampsia (PE) in relation to long and short sleep duration were estimated. Mean 1st and 2nd trimester systolic (S) and diastolic (D) BP values were similar among women reporting to be short sleepers (? 6 h) vs. women reporting to sleep 9 hours. However, both short and long sleep duration in early pregnancy were associated with increased mean 3rd trimester SBP and DBP. For example, mean 3rd trimester SBP was 3.72, and 2.43 mm Hg higher for women reporting ? 6 h and 7-8 h sleep, respectively, compared with women reporting 9 h of sleep. Mean 3rd trimester SBP was 4.21 mm Hg higher for women reporting long sleep (? 10 h) vs. the reference group. Short and long sleep durations were associated with increased risks of PIH and PE. The ORs for very short (< 5 h) and long (? 10 h) sleepers were 9.52 (95% CI 1.83 to 49.40) and 2.45 (95% CI 0.74 to 8.15) for PE. Conclusions: Our findings are consistent with a larger literature that documents elevated blood pressure and increased risks of hypertension with short and long sleep duration. Citation: Williams MA; Miller RS; Qiu C; Cripe SM; Gelaye B; Enquobahrie D. Associations of early pregnancy sleep duration with trimester-specific blood pressures and hypertensive disorders in pregnancy. SLEEP 2010;33(10):1363-1371.

Williams, Michelle A.; Miller, Raymond S.; Qiu, Chunfang; Cripe, Swee May; Gelaye, Bizu; Enquobahrie, Daniel

2010-01-01

130

Therapeutic efficacy of TBC3711 in monocrotaline-induced pulmonary hypertension  

Microsoft Academic Search

Background  Endothelin-1 signalling plays an important role in pathogenesis of pulmonary hypertension. Although different endothelin-A\\u000a receptor antagonists are developed, a novel therapeutic option to cure the disease is still needed. This study aims to investigate\\u000a the therapeutic efficacy of the selective endothelin-A receptor antagonist TBC3711 in monocrotaline-induced pulmonary hypertension\\u000a in rats.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Monocrotaline-injected male Sprague-Dawley rats were randomized and treated orally from

Djuro Kosanovic; Baktybek Kojonazarov; Himal Luitel; Bhola K Dahal; Akylbek Sydykov; Teodora Cornitescu; Wiebke Janssen; Ralf P Brandes; Neil Davie; Hossein A Ghofrani; Norbert Weissmann; Friedrich Grimminger; Werner Seeger; Ralph T Schermuly

2011-01-01

131

Propranolol reduces ethanol-induced gastric mucosal damage in portal hypertensive rats  

Microsoft Academic Search

In a standardized rat model of portal hypertension, we investigated the effects of propranolol on alcohol-induced gastric\\u000a mucosal damage. Portal hypertensive rats pretreated with 2 mg propranolol, compared with those receiving saline, had significantly\\u000a reduced portal pressures (24±1 vs 32±1 cm saline), macroscopic mucosal damage (24 ±1 vs 39±4% of mucosa), and histologic deep\\u000a necrosis (36±2 vs 61±4% of mucosal

H. Sankary; I. J. Sarfeh; A. Tarnawski; R. Maeda; K. J. Ivey; G. R. Mason

1986-01-01

132

[Modern methods of early screening for preeclampsia and pregnancy-induced hypertension--a review].  

PubMed

Preeclampsia remains to be a serious perinatal complication and early screening for this disease to identify the high risk population before the first symptoms develop constitutes a considerable clinical challenge. Modern methods of screening for preeclampsia and pregnancy-induced hypertension include patients history biochemical serum markers and foetal DNA and RNA in maternal serum. They aid the process of developing an optimal protocol to initiate treatment in early pregnancy and to reduce the rate of complications. Our review presents an overview of the novel methods and techniques used for early screening for preeclampsia and pregnancy-induced hypertension. Most of the research focuses on 11-13 weeks of gestation due to the fact that the first prenatal examination is performed at that time. The most important information seems to be: weight, mass, mean blood pressure, history of pregnancy-induced hypertension or preeclampsia at previous pregnancies as well as the ethnic origin. During an ultrasound scan, pulsatility index of the uterine arteries is measured. Blood samples are obtained during the last part of the examination. At the moment only a few markers seem to be strong predictors of hypertensive disorders during pregnancy: pregnancy-associated plasma protein-A (PAPP-A), placental growth factor (PIGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Also, fetal DNA and RNA in maternal plasma are helpful in the prediction of preeclampsia as they are markers of the trophoblast apoptosis. Researchers aim at identifying the population at high risk of pregnancy-induced hypertension and preeclampsia in order to offer appropriate antenatal care to these women. At the moment many drugs and diet supplements are investigated to reduce the prevalence of hypertensive disorders in pregnancy. These medications are usually administrated in early gestation (up to 16 week of gestation) before the first clinical symptoms present. Low doses of aspirin were found to decrease the risk of preeclampsia in high-risk groups. Moreover, according to some recent research, also essential omega-3 fatty acids reduce the incidence of preeclampsia. None of the other investigated diet supplements or antioxidants were proven to successfully reduce incidents of hypertensive disorders. So far, there is available evidence on the lack of any effect for vitamines C, D or E. Further studies are necessary to define clinical useful markers of gestational hypertension. PMID:23342898

Poprawski, Grzegorz; Wender-Ozegowska, Ewa; Zawiejska, Agnieszka; Brazert, Jacek

2012-09-01

133

Augmented sphingosylphosphorylcholine-induced Ca 2+ -sensitization of mesenteric artery contraction in spontaneously hypertensive rat  

Microsoft Academic Search

Sphingosylphosphorylcholine (SPC) is a vasoconstricting lysosphingolipid, and the RhoA\\/Rho-kinase pathway plays an important\\u000a role in SPC-induced contraction. Since RhoA\\/Rho-kinase-mediated signaling is involved in the generation and\\/or maintenance\\u000a of hypertension, we compared the effect of SPC on the contractility of endothelium-denuded small mesenteric arteries in spontaneously\\u000a hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Fura-2 Ca2+ signals, contractile responses, and phosphorylation

Sung-Kyung Ryu; Duck Sun Ahn; Young-Eun Cho; Soo-Kyung Choi; Young-Hwan Kim; Kathleen G. Morgan; Young-Ho Lee

2006-01-01

134

Cilnidipine lowered psychological stress-induced increase in blood pressure in a hypertensive man: a case report  

Microsoft Academic Search

BACKGROUND: In some hypertensive patients, psychological stress makes blood pressure difficult to control and causes physical symptoms such as headache or dizziness. We report the case of a hypertensive man whose psychological stress-induced increase in blood pressure was attenuated by cilnidipine. CASE PRESENTATION: The patient (a 72-year-old man) had hypertension and was on antihypertensive therapy. When mentally concentrating, he experienced

Sota Hayashida; Takakazu Oka; Sadatoshi Tsuji

2007-01-01

135

Enhanced NO Inactivation and Hypertension Induced by a High-Fat, Refined-Carbohydrate Diet  

Microsoft Academic Search

We have recently demonstrated that long-term consumption of a high-fat, refined-carbohydrate (HFS) diet induces hypertension (HTN) in normal rats compared with a low-fat, complex-carbohydrate (LFCC) diet. Limited evidence suggests that high-fat or high-sugar diets cause enhanced generation of reactive oxygen species (ROS). We therefore hypothesized that by inducing oxidative stress, the HFS diet may promote nitric oxide (NO) inactivation and

Christian K. Roberts; Nosratola D. Vaziri; Xiu Q. Wang; R. James Barnard

2010-01-01

136

Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats  

Microsoft Academic Search

Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats.BackgroundHyperuricemia has been associated with renal disease. Because glomerular hemodynamic alterations critically contribute to initiation and progression of renal disease, we evaluated the effect of mild hyperuricemia in glomerular microcirculatory changes in rats under normal conditions and with renal injury induced by subtotal renal ablation (RK).MethodsHyperuricemia was

Laura G. Sanchez-Lozada; EDILIA TAPIA; JOSÉ SANTAMARÍA; CARMEN AVILA-CASADO; VIRGILIA SOTO; TOMÁS NEPOMUCENO; BERNARDO RODRÍGUEZ-ITURBE; Richard J. Johnson; JAIME HERRERA-ACOSTA

2005-01-01

137

Ovariectomy Aggravated Sodium Induced Hypertension Associated With Altered Platelet Intracellular Ca2 in Dahl Rats  

Microsoft Academic Search

Our purpose was to determine the effect of ovariectomy on intracellular Ca2+ mobilization and platelet aggregation in sodium induced hypertension. At the age of 12 weeks ovariectomy or sham operation was performed in female Dahl-Iwai salt sensitive rats on a 0.3% NaCl diet. Four weeks later we assessed the effects of ovariectomy and an 8% NaCl diet on agonist induced

Keiichi Otsuka; Yoichi Ohno; Takayuki Sasaki; Hiroshi Yamakawa; Tomoko Hayashida; Taichi Suzawa; Hiromichi Suzuki; Takao Saruta

1997-01-01

138

Central interactions of aldosterone and angiotensin II in aldosterone- and angiotensin II-induced hypertension  

PubMed Central

Many studies have implicated both angiotensin II (ANG II) and aldosterone (Aldo) in the pathogenesis of hypertension, the progression of renal injury, and cardiac remodeling after myocardial infarction. In several cases, ANG II and Aldo have been shown to have synergistic interactions in the periphery. In the present studies, we tested the hypothesis that ANG II and Aldo interact centrally in Aldo- and ANG II-induced hypertension in male rats. In rats with blood pressure (BP) and heart rate (HR) measured by DSI telemetry, intracerebroventricular (icv) infusions of the mineralocorticoid receptor (MR) antagonists spironolactone and RU28318 or the angiotensin type 1 receptor (AT1R) antagonist irbesartan significantly inhibited Aldo-induced hypertension. In ANG II-induced hypertension, icv infusion of RU28318 significantly reduced the increase in BP. Moreover, icv infusions of the reactive oxygen species (ROS) scavenger tempol or the NADPH oxidase inhibitor apocynin attenuated Aldo-induced hypertension. To confirm these effects of pharmacological antagonists, icv injections of either recombinant adeno-associated virus carrying siRNA silencers of AT1aR (AT1aR-siRNA) or MR (MR-siRNA) significantly attenuated the development of Aldo-induced hypertension. The immunohistochemical and Western blot analyses of AT1aR-siRNA- or MR-siRNA-injected rats showed a marked reduction in the expression of AT1R or MR in the paraventricular nucleus compared with scrambled siRNA rats. When animals from all studies underwent ganglionic blockade with hexamethonium, there was a smaller reduction in the fall of BP in animals receiving icv AT1R or MR antagonists. These results suggest that ANG II and Aldo interact in the brain in a mutually cooperative manner such that the functional integrity of both brain AT1R and MR are necessary for hypertension to be induced by either systemic ANG II or Aldo. The pressor effects produced by systemic ANG II or Aldo involve increased central ROS and sympathetic outflow.

Beltz, Terry G.; Yu, Yang; Guo, Fang; Gomez-Sanchez, Celso E.; Hay, Meredith; Johnson, Alan Kim

2011-01-01

139

Evaluation of a Pumpless Lung Assist Device in Hypoxia-Induced Pulmonary Hypertension in Juvenile Piglets  

PubMed Central

Persistent pulmonary hypertension is an important cause of mortality and morbidity in term infants. The lung assist device (LAD) is a novel, pumpless, low-resistance extracorporeal oxygenator to supplement mechanical ventilation. The LAD may be associated with fewer complications compared to conventional extracorporeal membrane oxygenation. The objective is to test the feasibility and efficacy of the LAD in juvenile piglets with hypoxia-induced pulmonary hypertension. Pulmonary hypertension was acutely induced by hypoxia in six 3 – 4 week old acutely instrumented and intubated piglets. The LAD was attached between a carotid artery and jugular vein. Gas exchange and hemodynamic variables including pulmonary arterial pressure and cardiac output were measured. Successful LAD cannulation was achieved without complications in all animals. Extracorporeal shunt flow through the device averaged 18% of cardiac output. The LAD achieved oxygen delivery of 20% of total oxygen consumption. Pulmonary arterial pressure was reduced by 35% from 28±5 to 18±4 mm Hg (p<0.05) and systemic PaO2 increased by 33% from 27±2 to 36±4 mm Hg (p<0.05). Other hemodynamic variables remained stable. The novel LAD shows feasibility and efficacy in improving gas exchange and reducing pulmonary arterial pressures in a juvenile animal model of hypoxia-induced pulmonary hypertension.

El-Ferzli, George T.; Philips, Joseph B.; Bulger, Arlene; Ambalavanan, Namasivayam

2009-01-01

140

Myocardial blood flow during induced aortic hypertension in dogs  

SciTech Connect

Myocardial blood flow was measured in anesthetized dogs during control conditions and under conditions where the aortic pressure was increased due to aortic constriction or during infusion. Blood flow was measured using the radioactive microsphere technique. Radioactive microspheres (15 m Ce-141, Sr-85, and Sc-46) were injected under control, aortic constriction and arterenol infusion in four dogs and under control conditions in two others. All microsphere injections were performed under stabilized conditions. It was found that coronary blood flow rose by 80% during aortic constriction and by 158% during arterenol infusion (P < 0.05). This increase in blood flow was not uniform throughout the heart, and higher increases were observed in the middle and apex regions of the left ventricle. Furthermore, under hypertension the increase in blood flow in LAD (left anterior descending) perfused territories was slightly higher than that in CFX (left circumflex) perfused territories.

Thai, B.N.; Levesque, M.J.; Nerem, R.M.

1986-03-01

141

Irreversibility of Methylandrostenediol-Induced Hypertension in the Rat After Suspension of the Androgen Treatment  

PubMed Central

Administration of 10 mg of methylandrostenediol for 10 weeks to uninephrectomized, salt drinking, female Sprague Dawley rats caused severe hypertension with extensive renal and cardiovascular damage. The hypertension was accompanied by increased consumption of sodium, high sodium levels in peripheral plasma, decreased weight of the pituitary, thymus, adrenals and ovaries and decreased content of renal renin. Methylandrostenediol treatment also produced impairment of normal adrenal steroidogenesis, reflected in elevated production in vitro of 11-deoxycorticosterone during incubation of adrenal gland homogenates with 14C-progesterone. Such increased production of deoxycorticosterone is probably responsible for the development of the hypertensive disease. If the methylandrostenediol-treated animals were kept alive for 12 additional weeks after suspension of the treatment with the androgen, the hypertension, as well as the high sodium consumption, high plasma sodium concentrations and low levels of renal renin, persisted to the end of the experiment. The cardiovascular and renal lesions in these animals, killed 12 weeks after suspension of the androgen administration, were similar to those seen in the rats receiving methylandrostenediol but killed at the tenth week of the treatment. Suspension of methylandrostenediol administration, however, resulted in a return to normal weight of the pituitary, thymus, adrenals and ovaries within 12 weeks. Normal amounts of deoxycorticosterone were formed in vitro by the adrenal glands of these rats and the return to normal structure was also confirmed by a electron microscopic study. Thus, contrary to a previous experiment where methylandrostenediol was given for a shorter period of time and the hypertension was reversible, it was shown in this study that metacorticoid hypertension is induced by methylandrostenediol administration, as it is with treatment with deoxycorticosterone. Since adrenal steroidogenesis returned to normal, some other mechanisms must be involved in maintaining the hypertension. It is very likely that these factors are consequent to the extensive and irreversible renal and cardiovascular damage. ImagesFig 1Fig 2

Molteni, Agostino; Brownie, Alexander C.; Nickerson, Peter A.; Skelton, Floyd R.

1972-01-01

142

Hypertension Induced by VEGF Signaling Pathway Inhibition: Mechanisms and Potential Use as a Biomarker  

PubMed Central

Drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway are a rapidly growing chemotherapy class for treatment of solid tumors. This “targeted therapy” is more specific than traditional chemotherapy, causing fewer side effects. However, VEGF-targeted therapies cause hypertension in 30 – 80% of patients. Unlike traditional “off-target” side effects, hypertension is a mechanism-dependent, “on-target” toxicity – reflecting effective inhibition of the VEGF signaling pathway rather than non-specific effects on unrelated signaling pathways. In this article, we review current understanding of the mechanisms of VEGF-targeted therapy-induced hypertension, discuss similarities with preeclampsia, review implications for therapy of this increasingly common clinical problem and discuss the potential use of blood pressure rise as a biomarker for proper drug dosing and effective VEGF pathway inhibition.

Robinson, Emily S.; Khankin, Eliyahu V.; Karumanchi, S. Ananth; Humphreys, Benjamin D.

2010-01-01

143

[Role of estradiol in hypoxia-induced pulmonary hypertension in female rats].  

PubMed

Gender differences play role in pathogenesis and treatment of many cardiovascular diseases. One of these diseases is hypoxia-induced pulmonary hypertension (PHT). The aim of this study was to analyze the involvement of female hormone estradiol in development of hypoxia-induced PHT in female Wistar rats. PHT was induced by exposure to hypobaric hypoxia in an altitude chamber at a simulated altitude of 5000 m (02 concentration reduced to 10 %), 10 h per day for 2 weeks. The development of PHT leads to a twofold increase in the level of estradiol. Ovariectomy decreases by half the level of estradiol and causes significant decrease in hypoxia-induced PHT symptoms. PMID:23700662

Kovaleva, Iu O; Artem'eva, M M; Ilatovskaia, M E; Medvedev, O S; Medvedeva, N A

2012-01-01

144

Exercise-induced hypertension among healthy firefighters-a comparison between two different definitions.  

PubMed

Different studies have yielded conflicting results regarding the association of hypertensive response to exercise and cardiovascular morbidity. We compared two different definitions of exaggerated hypertensive response to exercise and their association with cardio-respiratory fitness in a population of healthy firefighters. We examined blood pressure response to exercise in 720 normotensive male career firefighters. Fitness was measured as peak metabolic equivalent tasks (METs) achieved during maximal exercise treadmill tests. Abnormal hypertensive response was defined either as systolic blood pressure ? 200 mm Hg; or alternatively, as responses falling in the upper tertile of blood pressure change from rest to exertion, divided by the maximal workload achieved. Using the simple definition of a 200 mm Hg cutoff at peak exercise less fit individuals (METs ? 12) were protected from an exaggerated hypertensive response (OR 0.45, 95%CI 0.30-0.67). However, using the definition of exercise-induced hypertension that corrects for maximal workload, less fit firefighters had almost twice the risk (OR 1.8, 95%CI 1.3-2.47). Blood pressure change corrected for maximal workload is better correlated with cardiorespiratory fitness. Systolic blood pressure elevation during peak exercise likely represents an adaptive response, whereas elevation out of proportion to the maximal workload may indicate insufficient vasodilation and a maladaptive response. Prospective studies are needed to best define exaggerated blood pressure response to exercise. PMID:23246464

Leiba, Adi; Baur, Dorothee M; Kales, Stefanos N

2012-12-14

145

The role of salt in the pathogenesis of fructose-induced hypertension.  

PubMed

Metabolic syndrome, as manifested by visceral obesity, hypertension, insulin resistance, and dyslipidemia, is reaching epidemic proportions in the Western World, specifically the United States. Epidemiologic studies suggest that the increased prevalence of metabolic syndrome directly correlates with an increase in the consumption of fructose, mainly in the form of high-fructose corn syrup. This inexpensive alternative to traditional sugar has been increasingly utilized by the food industry as a sweetener since the 1960s. While augmented caloric intake and sedentary lifestyles play important roles in the increasing prevalence of obesity, the pathogenesis of hypertension in metabolic syndrome remains controversial. One intriguing observation points to the role of salt in fructose-induced hypertension. Recent studies in rodents demonstrate that increased dietary fructose intake stimulates salt absorption in the small intestine and kidney tubules, resulting in a state of salt overload, thus setting in motion a cascade of events that will lead to hypertension. These studies point to a novel interaction between the fructose-absorbing transporter, Glut5, and the salt transporters, NHE3 and PAT1, in the intestine and kidney proximal tubule. This paper will focus on synergistic roles of fructose and salt in the pathogenesis of hypertension resulting from salt overload. PMID:21789281

Soleimani, Manoocher; Alborzi, Pooneh

2011-07-18

146

The time course of salt-induced hypertension, and why it matters.  

PubMed

The epidemiology of salt-induced hypertension has been explored in detail in animal studies, in some cases involving exposures to excess dietary salt for much of the animal's lifespan. The results of these studies demonstrate the presence of two distinct time courses of the blood pressure response to a high salt intake: an acute (rapid) blood pressure response occurring over days to weeks, and a slow and progressive blood pressure response that develops over extremely long periods of time, amounting to a significant fraction of the lifespan in normal individuals. The acute form of salt sensitivity is well known in humans, having often been demonstrated as a fall in blood pressure during the period of salt restriction. The slow and progressive form of salt sensitivity has been demonstrated directly in rats and chimpanzees and is also evident in analyses of human cross-population data as a salt dependency of age-associated changes of blood pressure. This slow and progressive component of salt-induced hypertension may be attributable, at least in part, to a progressive rise in the acute salt sensitivity of blood pressure during sustained exposure to high salt. However, a progressively irreversible or 'self sustaining' component of salt-induced hypertension has also been demonstrated in rat studies. This irreversible component has not been completely characterized, but its presence raises the possibility that blood pressure responses to salt restriction may not fully reveal the contribution of salt to blood pressure or the epidemiology of hypertension. These various components of salt sensitivity (acute vs slow, reversible vs irreversible) should be considered in any comprehensive explanation of the effects of salt on blood pressure and especially in experimental studies of the genetic and physiological mechanisms underlying salt-induced hypertension. PMID:19079278

Van Vliet, B N; Montani, J-P

2008-12-01

147

Nerve stimulation induced overflow of neuropeptide Y and modulation by angiotensin II in spontaneously hypertensive rats.  

PubMed

The sympathetic nervous system and renin-angiotensin system are both thought to contribute to the development and maintenance of hypertension in experimental models such as the spontaneously hypertensive rat (SHR). We demonstrated that periarterial nerve stimulation (NS) increased the perfusion pressure (PP) and neuropeptide Y (NPY) overflow from perfused mesenteric arterial beds of SHRs at 4-6, 10-12, and 18-20 wk of age, which correspond to prehypertensive, developing hypertensive, and maintained hypertensive stages, respectively, in the SHR. NS also increased PP and NPY overflow from mesenteric beds of Wistar-Kyoto (WKY) normotensive rats. NS-induced increases in PP and NPY were greater in vessels obtained from SHRs of all three ages compared with WKY rats. ANG II produced a greater increase in PP in preparations taken from SHRs than WKY rats. ANG II also resulted in a greater increase in basal NPY overflow from 10- to 12-wk-old and 18- to 20-wk-old SHRs than age-matched WKY rats. ANG II enhanced the NS-induced overflow of NPY from SHR preparations more than WKY controls at all ages studied. The enhancement of NS-induced NPY overflow by ANG II was blocked by the AT1 receptor antagonist EMD-66684 and the angiotensin type 2 receptor antagonist PD-123319. In contrast, ANG II greatly enhanced norepinephrine overflow in the presence of PD-123319. Both captopril and EMD-66684 decreased neurotransmitter overflow from SHR mesenteric beds; therefore, we conclude that an endogenous renin-angiotensin system is active in this preparation. It is concluded that the ANG II-induced enhancement of sympathetic nerve stimulation may contribute to the development and maintenance of hypertension in the SHR. PMID:18835922

Byku, Mirnela; Macarthur, Heather; Westfall, Thomas C

2008-10-03

148

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

PubMed Central

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.

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

2012-01-01

149

NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice  

PubMed Central

Pulmonary hypertension occurs with prolonged exposure to chronic hypoxia in both adults and neonates. The Ca2+-dependent transcription factor, nuclear factor of activated T cells isoform c3 (NFATc3), has been implicated in chronic hypoxia-induced pulmonary arterial remodeling in adult mice. Therefore, we hypothesized that NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice. The aim of this study was to determine whether 1) NFATc3 mediates chronic hypoxia-induced increases in right ventricular systolic pressure in adult mice; 2) NFATc3 is activated in neonatal mice exposed to chronic hypoxia; and 3) NFATc3 is involved in chronic hypoxia-induced right ventricular hypertrophy and pulmonary vascular remodeling in neonatal mice. Adult mice were exposed to hypobaric hypoxia for 2, 7, and 21 days. Neonatal mouse pups were exposed for 7 days to hypobaric chronic hypoxia within 2 days after delivery. Hypoxia-induced increases in right ventricular systolic pressure were absent in NFATc3 knockout adult mice. In neonatal mice, chronic hypoxia caused NFAT activation in whole lung and nuclear accumulation of NFATc3 in both pulmonary vascular smooth muscle and endothelial cells. In addition, heterozygous NFATc3 neonates showed less right ventricular hypertrophy and pulmonary artery wall thickness in response to chronic hypoxia than did wild-type neonates. Our results suggest that NFATc3 mediates pulmonary hypertension and vascular remodeling in both adult and neonatal mice.

Bierer, R.; Nitta, C. H.; Friedman, J.; Codianni, S.; de Frutos, S.; Dominguez-Bautista, J. A.; Howard, T. A.; Resta, T. C.

2011-01-01

150

NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice.  

PubMed

Pulmonary hypertension occurs with prolonged exposure to chronic hypoxia in both adults and neonates. The Ca(2+)-dependent transcription factor, nuclear factor of activated T cells isoform c3 (NFATc3), has been implicated in chronic hypoxia-induced pulmonary arterial remodeling in adult mice. Therefore, we hypothesized that NFATc3 is required for chronic hypoxia-induced pulmonary hypertension in adult and neonatal mice. The aim of this study was to determine whether 1) NFATc3 mediates chronic hypoxia-induced increases in right ventricular systolic pressure in adult mice; 2) NFATc3 is activated in neonatal mice exposed to chronic hypoxia; and 3) NFATc3 is involved in chronic hypoxia-induced right ventricular hypertrophy and pulmonary vascular remodeling in neonatal mice. Adult mice were exposed to hypobaric hypoxia for 2, 7, and 21 days. Neonatal mouse pups were exposed for 7 days to hypobaric chronic hypoxia within 2 days after delivery. Hypoxia-induced increases in right ventricular systolic pressure were absent in NFATc3 knockout adult mice. In neonatal mice, chronic hypoxia caused NFAT activation in whole lung and nuclear accumulation of NFATc3 in both pulmonary vascular smooth muscle and endothelial cells. In addition, heterozygous NFATc3 neonates showed less right ventricular hypertrophy and pulmonary artery wall thickness in response to chronic hypoxia than did wild-type neonates. Our results suggest that NFATc3 mediates pulmonary hypertension and vascular remodeling in both adult and neonatal mice. PMID:21908592

Bierer, R; Nitta, C H; Friedman, J; Codianni, S; de Frutos, S; Dominguez-Bautista, J A; Howard, T A; Resta, T C; Bosc, L V Gonzalez

2011-09-09

151

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

Microsoft Academic Search

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

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

152

Myocilin Gene Expression in the Trabecular Meshwork of Rats in a Steroid-Induced Ocular Hypertension Model  

Microsoft Academic Search

Purpose: To investigate the expression pattern of myocilin in the trabecular meshwork of normal and dexamethasone-induced ocular hypertensive rat eyes. Materials and Methods: An ocular hypertension model was generated by application of topical dexamethasone to rat eyes 4 times daily for 1, 2, and 4 weeks. Age-matched untreated eyes served as controls. The intraocular pressure (IOP) was monitored by electronic

Keiko Sawaguchi; Yoshimi Nakamura; Yuko Nakamura; Hiroshi Sakai; Shoichi Sawaguchi

2005-01-01

153

Mechanisms of lead-induced hypertension and cardiovascular disease  

PubMed Central

Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic illnesses. Population studies have demonstrated a link between lead exposure and subsequent development of hypertension (HTN) and cardiovascular disease. In vivo and in vitro studies have shown that chronic lead exposure causes HTN and cardiovascular disease by promoting oxidative stress, limiting nitric oxide availability, impairing nitric oxide signaling, augmenting adrenergic activity, increasing endothelin production, altering the renin-angiotensin system, raising vasoconstrictor prostaglandins, lowering vasodilator prostaglandins, promoting inflammation, disturbing vascular smooth muscle Ca2+ signaling, diminishing endothelium-dependent vasorelaxation, and modifying the vascular response to vasoactive agonists. Moreover, lead has been shown to cause endothelial injury, impede endothelial repair, inhibit angiogenesis, reduce endothelial cell growth, suppress proteoglycan production, stimulate vascular smooth muscle cell proliferation and phenotypic transformation, reduce tissue plasminogen activator, and raise plasminogen activator inhibitor-1 production. Via these and other actions, lead exposure causes HTN and promotes arteriosclerosis, atherosclerosis, thrombosis, and cardiovascular disease. In conclusion, studies performed in experimental animals, isolated tissues, and cultured cells have provided compelling evidence that chronic exposure to low levels of lead can cause HTN, endothelial injury/dysfunction, arteriosclerosis, and cardiovascular disease. More importantly, these studies have elucidated the cellular and molecular mechanisms of lead's action on cardiovascular/renal systems, a task that is impossible to accomplish using clinical and epidemiological investigations alone.

Vaziri, Nosratola D.

2008-01-01

154

Smad3 mediates ANG II-induced hypertensive kidney disease in mice.  

PubMed

Although Smad3 is a key mediator for fibrosis, its functional role and mechanisms in hypertensive nephropathy remain largely unclear. This was examined in the present study in a mouse model of hypertension induced in Smad3 knockout (KO) and wild-type (WT) mice by subcutaneous angiotensin II infusion and in vitro in mesangial cells lacking Smad3. After angiotensin II infusion, both Smad3 KO and WT mice developed equally high levels of blood pressure. However, disruption of Smad3 prevented angiotensin II-induced kidney injury by lowering albuminuria and serum creatinine (P < 0.01), inhibiting renal fibrosis such as collagen type I and IV, fibronectin, and ?-SMA expression (all P < 0.01), and blocking renal inflammation including macrophage and T cell infiltration and upregulation of IL-1?, TNF-?, and monocyte chemoattractant protein-1 in vivo and in vitro (all P < 0.001). Further studies revealed that blockade of angiotensin II-induced renal transforming growth factor (TGF)-?1 expression and inhibition of Smurf2-mediated degradation of renal Smad7 are mechanisms by which Smad3 KO mice were protected from angiotensin II-induced renal fibrosis and NF-?B-driven renal inflammation in vivo and in vitro. In conclusion, Smad3 is a key mediator of hypertensive nephropathy. Smad3 promotes Smurf2-dependent ubiquitin degradation of renal Smad7, thereby enhancing angiotensin II-induced TGF-?/Smad3-mediated renal fibrosis and NF-?B-driven renal inflammation. Results from this study suggest that inhibition of Smad3 or overexpression of Smad7 may be a novel therapeutic strategy for hypertensive nephropathy. PMID:22237801

Liu, Zhen; Huang, Xiao R; Lan, Hui Y

2012-01-11

155

Role of thromboxane A2 in early BDL-induced portal hypertension.  

PubMed

Although the mechanisms of cirrhosis-induced portal hypertension have been studied extensively, the role of thromboxane A(2) (TXA(2)) in the development of portal hypertension has never been explicitly explored. In the present study, we sought to determine the role of TXA(2) in bile duct ligation (BDL)-induced portal hypertension in Sprague-Dawley rats. After 1 wk of BDL or sham operation, the liver was isolated and perfused with Krebs-Henseleit bicarbonate buffer at a constant flow rate. After 30 min of nonrecirculating perfusion, the buffer was recirculated in a total volume of 100 ml. The perfusate was sampled for the enzyme immunoassay of thromboxane B(2) (TXB(2)), the stable metabolite of TXA(2). Although recirculation of the buffer caused no significant change in sham-operated rats, it resulted in a marked increase in portal pressure in BDL rats. The increase in portal pressure was found concomitantly with a significant increase of TXB(2) in the perfusate (sham vs. BDL after 30 min of recirculating perfusion: 1,420 +/- 803 vs. 10,210 +/- 2,950 pg/ml; P < 0.05). Perfusion with a buffer containing indomethacin or gadolinium chloride for inhibition of cyclooxygenase (COX) or Kupffer cells, respectively, substantially blocked the recirculation-induced increases in both portal pressure and TXB(2) release in BDL group. Hepatic detection of COX gene expression by RT-PCR revealed that COX-2 but not COX-1 was upregulated following BDL, and this upregulation was confirmed at the protein level by Western blot analysis. In conclusion, these results clearly demonstrate that increased hepatic TXA(2) release into the portal circulation contributes to the increased portal resistance in BDL-induced liver injury, suggesting a role of TXA(2) in liver fibrosis-induced portal hypertension. Furthermore, the Kupffer cell is likely the source of increased TXA(2), which is associated with upregulation of the COX-2 enzyme. PMID:12431905

Yokoyama, Yukihiro; Xu, Hongzhi; Kresge, Nicole; Keller, Steve; Sarmadi, Amir H; Baveja, Rajiv; Clemens, Mark G; Zhang, Jian X

2002-11-13

156

Etoricoxib Attenuates Effect of Antihypertensives in a Rodent Model of DOCA-Salt Induced Hypertension.  

PubMed

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

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

2013-03-14

157

Effects of losartan on the blood–brain barrier permeability in long-term nitric oxide blockade-induced hypertensive rats  

Microsoft Academic Search

Hypertension is closely associated with vascular endothelial dysfunction. The aim of this study was to investigate the effects of Angiotensin II (ANG II) receptor antagonist losartan on the blood–brain barrier (BBB) permeability in L-NAME-induced hypertension and\\/or in ANG II-induced acute hypertension in normotensive and hypertensive rats. Systolic blood pressure was measured by tail cuff method before, during and following L-NAME

Mutlu Kucuk; Mehmet Kaya; Rivaze Kalayci; Vedat Cimen; Hasan Kudat; Nadir Arican; Imdat Elmas; Ferruh Korkut

2002-01-01

158

Concordance of Murine Quantitative Trait Loci for Salt-Induced Hypertension with Rat and Human Loci  

Microsoft Academic Search

To investigate the genetic control of salt-induced hypertension, we performed a quantitative trait locus analysis on male mice from a reciprocal backcross between the salt-sensitive C57BL\\/6J and the normotensive A\\/J inbred mouse strains after they were provided with water containing 1% salt for 2 weeks. Genome-wide scans performed on these mice and analyzed with a combination of conventional marker-based regressions

Fumihiro Sugiyama; Gary A. Churchill; David C. Higgins; Conrado Johns; Konstatinos P. Makaritsis; Haralambos Gavras; Beverly Paigen

2001-01-01

159

Rats with steroid-induced polycystic ovaries develop hypertension and increased sympathetic nervous system activity  

Microsoft Academic Search

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder associated with ovulatory dysfunction, abdominal obesity, hyperandrogenism, hypertension, and insulin resistance. METHODS: Our objectives in this study were (1) to estimate sympathetic-adrenal medullary (SAM) activity by measuring mean systolic blood pressure (MSAP) in rats with estradiol valerate (EV)-induced PCO; (2) to estimate alpha1a and alpha2a adrenoceptor expression in

Elisabet Stener-Victorin; Karolina Ploj; Britt-Mari Larsson; Agneta Holmäng

2005-01-01

160

Superoxide Generation and Reversal of Acetylcholine Induced Cerebral Arteriolar Dilation after Acute Hypertension  

Microsoft Academic Search

SUMMARY. The appearance of superoxide anion radical in cerebral extracellular space during and after acute hypertension induced by intravenous norepinephrine was investigated in anes- thetized cats equipped with cranial windows. Superoxide was detected by demonstrating the presence of superoxide dismutase-inhibitable reduction of nitroblue tetrazolium. The superoxide dismutase-inhibitable rate of reduction of nitroblue tetrazolium was 4.1 ± 1.61 nM\\/min per cm2

Enoch P. Wei; Hermes A. Kontos; Carole W. Christman; Douglas S. DeWitt; John T. Povlishock

2009-01-01

161

Interstitial Cells of Cajal in Abdominal Sepsis and Hypertension-Induced Ileus in Rats  

Microsoft Academic Search

Purpose: To evaluate injury to the myenteric interstitial cells of Cajal (ICC-MY) and assess the role of ICC-MY in gastrointestinal motility in rat models of abdominal sepsis and intra-abdominal hypertension (IAH). Materials and Methods: Sprague-Dawley rats were divided into 4 groups; group 1: sham group; group 2: sepsis induced by cecal puncture and ligation; group 3: IAH created by placing

Zheng Lou; Jie Shou Li

2009-01-01

162

Analysis of heart rate variability in a rat model of induced pulmonary hypertension  

Microsoft Academic Search

Monocrotaline (MCT) is commonly used to experimentally induce pulmonary hypertension (PH), which might lead to chronic heart failure. In this study, linear and non-linear heart rate (HR) dynamics were weekly assessed in MCT-treated and non-treated Wistar rats.The HR of 10 adult Wistar rats injected with MCT (MCT group) and of 10 similar rats injected with vehicle (non-MCT group), anesthetized with

Hernâni Gonçalves; Tiago Henriques-Coelho; João Bernardes; Ana Paula Rocha; Ana Brandão-Nogueira; Adelino Leite-Moreira

2010-01-01

163

2-methoxyestradiol attenuates bleomycin-induced pulmonary hypertension and fibrosis in estrogen-deficient rats  

Microsoft Academic Search

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

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

2009-01-01

164

Effects of Everolimus in Combination with Sildenafil in Monocrotaline-induced Pulmonary Hypertension in Rats  

Microsoft Academic Search

In our study, we investigated the efficacy of everolimus in combination with sildenafil on hemodynamic and morphological parameters\\u000a in rats with monocrotaline-induced pulmonary hypertension (PH). Right ventricular pressure (RVP), right ventricular hypertrophy,\\u000a and the response to vasoconstrictor and vasodilator agents in pulmonary arteries as evaluated by myography and histopathological\\u000a changes were compared among the groups. RVP and right ventricle\\/body weight

Sinem Ilgin; Dilek Burukoglu; Ozlem Atli; Basar Sirmagul

165

Development of Monocrotaline-Induced Pulmonary Hypertension Is Attenuated by a Serotonin Receptor Antagonist  

Microsoft Academic Search

.   The significance of serotonin in the pathogenesis of monocrotaline-induced pulmonary hypertension (MCT-PH) in rats, plasma\\u000a serotonin concentrations, and the effect of a serotonin receptor antagonist administration in association with the number\\u000a of proliferative cells were investigated. The thickness of the media of the small pulmonary arteries and the weight ratio\\u000a of the RV to that of LV + S

M. Miyata; M. Ito; T. Sasajima; H. Ohira; Y. Sato; R. Kasukawa

2000-01-01

166

Inhibition of the soluble epoxide hydrolase attenuates monocrotaline-induced pulmonary hypertension in rats  

PubMed Central

Objectives The soluble epoxide hydrolase (sEH) metabolizes epoxyeicosatrienoic acids (EETs) to their less active dihydroxy derivatives. Because EETs have anti-inflammatory properties, we determined whether or not inhibition of sEH attenuates disease development in the monocrotaline model of pulmonary hypertension in rats. Methods sEH inhibition was achieved using 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (25 mg/l) and cis-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (5 mg/l) administered via drinking water starting 3 days prior to monocrotaline injection (60 mg/kg). Results Monocrotaline induced the development of progressive pulmonary hypertension. sEH inhibition increased the plasma ratio of EETs to DHETs and attenuated the monocrotaline-induced increase in pulmonary artery medial wall thickness as well as the degree of vascular muscularization. Moreover, right ventricular pressure was significantly lower in the group treated with sEH inhibitors. Pulmonary sEH protein expression and sEH activity, as well as pulmonary cytochrome P450 epoxygenase activity were all impaired in monocrotaline-treated rats as compared with control animals. sEH inhibitors, however, increased the plasma ratio of EETs to dihydroxy epoxyeicosatrienoic acids. Monocrotaline induced the proliferation of pulmonary endothelial and vascular smooth muscle cells in vivo as determined by 5-Bromo-2?-deoxy-Uridine incorporation, and this effect was significantly blunted in animals treated with sEH inhibitors. Proliferation of cultured pulmonary smooth muscle cell, however, was not affected by EETs or sEH inhibitors suggesting that the in-vivo effects are a consequence of a direct EET-mediated protection against the inflammation induced by monocrotaline. Conclusion sEH inhibition reduces pulmonary vascular remodeling and the development of pulmonary hypertension in the monocrotaline model of primary pulmonary hypertension in rats.

Revermann, Marc; Barbosa-Sicard, Eduardo; Dony, Eva; Schermuly, Ralph T.; Morisseau, Christophe; Geisslinger, Gerd; Fleming, Ingrid; Hammock, Bruce D.; Brandes, Ralf P.

2010-01-01

167

Simvastatin Inhibits Cigarette Smoking-induced Emphysema and Pulmonary Hypertension in Rat Lungs  

Microsoft Academic Search

Rationale: In cigarette smoking-induced chronic obstructive pulmo- nary disease, structural and functional derangements are character- ized by parenchymal destruction and pulmonary hypertension. Statins are 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase in- hibitors that have been used as lipid-lowering agents. These drugs also have additional pharmacologic properties, including anti- inflammation, scavenging reactive oxygen species, restoring endo- thelial function, and antithrombogenesis, all of which can counter-

Ji-Hyun Lee; Dong-Soon Lee; Eun-Kyung Kim; Kang-Hyeon Choe; Yeon-Mock Oh; Tae-Sun Shim; Sang-Eun Kim; Yun-Song Lee; Sang-Do Lee

2005-01-01

168

Arthritis Induced by Adjuvant in Spontaneously Hypertensive and Normotensive Rats: Endogenous Glucocorticoid Effects on Inflammatory Response  

Microsoft Academic Search

The present study investigated arthritis induced by complete Freund adjuvant (AIA) in spontaneously hypertensive and normotensive\\u000a rats (respectively, SHR and NTR rats). The inflammatory reaction was studied for 28 days by evaluating paw edema and secondary\\u000a lesions found 10 days after complete Freund adjuvant (CFA) administration. The body weight of the animals and macroscopic\\u000a alterations of several organs, including spleen, thymus, adrenal

Micheli G. Torres; Fabio H. Kwasniewski; Luís G. Scaliante; Emy L. Ishii-Iwamoto; Silvana M. Caparroz-Assef; Roberto K. N. Cuman; Ciomar A. Bersani-Amado

2009-01-01

169

Reversal of cadmium?induced hypertension by d?myo?inositol?1,2,6?trisphosphate  

Microsoft Academic Search

The aim of this experiment was to test whether a chelating agent, D?myo?inositol?1,2,6?trisphosphate (PP56), could reverse cadmium?induced hypertension. Four groups of weanling female Long?Evans rats received ad libitum a rye?based, metal?poor diet and deionized water fortified with essential metals for 15 mo from the time of weaning. A control group received neither cadmium nor chelating agent. A second group had

H. Mitchell Perry Jr; Margaret W. Erlanger; Torgny O. Gustafsson; Elizabeth F. Perry

1989-01-01

170

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

Microsoft Academic Search

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

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

171

The Proportion of Individuals with Alcohol-Induced Hypertension among Total Hypertensives in a General Japanese Population: NIPPON DATA90  

Microsoft Academic Search

Japanese men consume more alcoholic beverages than men in many other developed countries. The high consumption rate of alcoholic beverages among Japanese men may contribute to the high prevalence of hypertension in Japan. In the present study, we calculated the odds ratio for hypertension in alcohol drinkers based on recent criteria using data from a nationwide survey conducted in Japan

Koshi Nakamura; Tomonori Okamura; Takehito Hayakawa; Atsushi Hozawa; Takashi Kadowaki; Yoshitaka Murakami; Yoshikuni Kita; Akira Okayama; Hirotsugu Ueshima

2007-01-01

172

Atorvastatin prevented and reversed dexamethasone-induced hypertension in the rat.  

PubMed

To assess the antioxidant effects of atorvastatin (atorva) on dexamethasone (dex)-induced hypertension, 60 male Sprague-Dawley rats were treated with atorva 30 mg/kg/day or tap water for 15 days. Dex increased systolic blood pressure (SBP) from 109 +/- 1.8 to 135 +/- 0.6 mmHg and plasma superoxide (5711 +/- 284.9 saline, 7931 +/- 392.8 U/ml dex, P < 0.001). In this prevention study, SBP in the atorva + dex group was increased from 115 +/- 0.4 to 124 +/- 1.5 mmHg, but this was significantly lower than in the dex-only group (P' < 0.05). Atorva reversed dex-induced hypertension (129 +/- 0.6 mmHg, vs. 135 +/- 0.6 mmHg P' < 0.05) and decreased plasma superoxide (7931 +/- 392.8 dex, 1187 +/- 441.2 atorva + dex, P < 0.0001). Plasma nitrate/nitrite (NOx) was decreased in dex-treated rats compared to saline-treated rats (11.2 +/- 1.08 microm, 15.3 +/- 1.17 microm, respectively, P < 0.05). Atorva affected neither plasma NOx nor thymus weight. Thus, atorvastatin prevented and reversed dexamethasone-induced hypertension in the rat. PMID:16820346

Mondo, Charles Kiiza; Yang, Wan-Song; Su, Ji-Zhou; Huang, Ti-Gang

2006-07-01

173

Prenatal programming of hypertension induces sympathetic overactivity in response to physical stress.  

PubMed

Small-for-gestational-age infants are known to develop hypertension in adulthood. This prenatal programming of hypertension (PPH) can result from several insults including maternal dietary protein deprivation, uteroplacental insufficiency, and prenatal administration of glucocorticoids. The mechanisms underlying the development of hypertension remain unclear although the sympathetic nervous system has been indirectly implicated. This study was designed to directly measure renal sympathetic nerve activity both at rest and during physical stress in an animal model of PPH. The adult male offspring of rats fed either a 6% (PPH) or 20% protein diet (control) were investigated. Conscious systolic blood pressure measured by tail cuff was significantly higher in PPH compared with control (140 ± 3 versus 128 ± 3 mm Hg; P<0.05). Baseline mean arterial pressure, heart rate, and renal sympathetic activity were not different between groups during isoflurane anesthesia or after decerebration. Physical stress was induced in decerebrate animals by activating the exercise pressor reflex during static muscle contraction. Stimulation of the exercise pressor reflex evoked significantly larger changes from baseline in mean arterial pressure (40 ± 7 versus 20 ± 4 mm Hg; P<0.05), heart rate (19 ± 3 versus 5 ± 1 bpm; P<0.05), and renal sympathetic activity (198 ± 29% versus 68 ± 14%; P<0.05) in PPH as compared with control. The data demonstrate that the sympathetic response to physical stress is markedly exaggerated in PPH and may play a significant role in the development of hypertension in adults born small for gestational age. PMID:23150514

Mizuno, Masaki; Siddique, Khurrum; Baum, Michel; Smith, Scott A

2012-11-12

174

Estrogen normalizes perinatal nicotine-induced hypertensive responses in adult female rat offspring.  

PubMed

Perinatal nicotine exposure caused a sex-dependent heightened vascular response to angiotensin II (Ang II) and increased blood pressure in adult male but not in female rat offspring. The present study tested the hypothesis that estrogen normalizes perinatal nicotine-induced hypertensive response to Ang II in female offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth. Ovariectomy and 17?-estradiol replacement were performed on 8-week-old female offspring. At 5 months of age, Ang II-induced blood pressure responses were not changed by nicotine treatment in the sham groups. In contrast, nicotine significantly enhanced Ang II-induced blood pressure responses as compared with saline control in the ovariectomy groups, which was associated with increased Ang II-induced vascular contractions. These heightened responses were abrogated by 17?-estradiol replacement. In addition, nicotine enhanced Ang II receptor type I, NADPH (nicotinamide adenine dinucleotide phosphate) oxidase type 2 protein expressions, and reactive oxygen species production of aortas as compared with saline control in the ovariectomy groups. Antioxidative agents, both apocynin and tempol, inhibited Ang II-induced vascular contraction and eliminated the differences of contractions between nicotine-treated and control ovariectomy rats. These findings support a key role of estrogen in the sex difference of perinatal nicotine-induced programming of vascular dysfunction, and suggest that estrogen may counteract heightened reactive oxygen species production, leading to protection of females from development programming of hypertensive phenotype in adulthood. PMID:23529162

Xiao, Daliao; Huang, Xiaohui; Yang, Shumei; Zhang, Lubo

2013-03-25

175

Anomalous Signature Splitting of the pih 1/2 otimesnui 3/2 Band in A~ 160 Odd Odd Nuclei  

NASA Astrophysics Data System (ADS)

Systematic features of anomalous signature splitting of the pih 11/2otimesnui 13/2 band in A~160 odd-odd nuclei have been investigated. It is shown that the mechanism of anomalous signature splitting is similar to that of the normal signature splitting which is essentially caused by the Coriolis mixing of Omega = 1/2 components into the nuclear wavefunction and the anomalous splitting in signature is mainly caused by the definition. The extensively observed anomalous signature splitting in this band might be an indication that the interaction between the h 11/2 proton and the i 13/2 neutron cannot be neglected. The new observation of high- and low-K bands based on the same pih 11/2otimesnui 13/2 configuration in 164Tm is also discussed.

Yang, Chun-Xiang; Zhou, Hong-Yu

2003-12-01

176

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

PubMed Central

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.

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

177

Cyclooxygenase-2-linked attenuation of hypoxia-induced pulmonary hypertension and intravascular thrombosis.  

PubMed

Exogenous prostacyclin is effective in reducing pulmonary vascular resistance in some forms of human pulmonary hypertension (PH). To explore whether endogenous prostaglandins played a similar role in pulmonary hypertension, we examined the effect of deleting cyclooxygenase (COX)-gene isoforms in a chronic hypoxia model of PH. Pulmonary hypertension, examined by direct measurement of right ventricular end systolic pressure (RVESP), right ventricular hypertrophy (n = 8), and hematocrit (n = 3), was induced by 3 weeks of hypobaric-hypoxia in wild-type and COX-knockout (KO) mice. RVESP was increased in wild-type hypoxic mice compared with normoxic controls (24.4 +/- 1.4 versus 13.8 +/- 1.9 mm Hg; n = 8; p < 0.05). COX-2 KO mice showed a greater increase in RVESP following hypoxia (36.8 +/- 2.7 mm Hg; p < 0.05). Urinary thromboxane (TX)B(2) excretion increased following hypoxia (44.6 +/- 11.1 versus 14.7 +/- 1.8 ng/ml; n = 6; p < 0.05), an effect that was exacerbated by COX-2 gene disruption (54.5 +/- 10.8 ng/ml; n = 6). In contrast, the increase in 6-keto-prostacyclin(1alpha) excretion following hypoxia was reduced by COX-2 gene disruption (29 +/- 3 versus 52 +/- 4.6 ng/ml; p < 0.01). Tail cut bleed times were lower following hypoxia, and there was evidence of intravascular thrombosis in lung vessels that was exacerbated by disruption of COX-2 and reduced by deletion of COX-1. The TXA(2)/endoperoxide receptor antagonist ifetroban (50 mg/kg/day) offset the effect of deleting the COX-2 gene, attenuating the hypoxia-induced rise in RVESP and intravascular thrombosis. COX-2 gene deletion exacerbates pulmonary hypertension, enhances sensitivity to TXA(2), and induces intravascular thrombosis in response to hypoxia. The data provide evidence that endogenous prostaglandins modulate the pulmonary response to hypoxia. PMID:18375790

Cathcart, Mary-Clare; Tamosiuniene, Rasa; Chen, Gang; Neilan, Tomas G; Bradford, Aidan; O'Byrne, Kenneth J; Fitzgerald, Desmond J; Pidgeon, Graham P

2008-03-28

178

Neuroinflammation and oxidative stress in rostral ventrolateral medulla contribute to neurogenic hypertension induced by systemic inflammation  

PubMed Central

Background In addition to systemic inflammation, neuroinflammation in the brain, which enhances sympathetic drive, plays a significant role in cardiovascular diseases, including hypertension. Oxidative stress in rostral ventrolateral medulla (RVLM) that augments sympathetic outflow to blood vessels is involved in neural mechanism of hypertension. We investigated whether neuroinflammation and oxidative stress in RVLM contribute to hypertension following chronic systemic inflammation. Methods In normotensive Sprague-Dawley rats, systemic inflammation was induced by infusion of Escherichia coli lipopolysaccharide (LPS) into the peritoneal cavity via an osmotic minipump. Systemic arterial pressure and heart rate were measured under conscious conditions by the non-invasive tail-cuff method. The level of the inflammatory markers in plasma or RVLM was analyzed by ELISA. Protein expression was evaluated by Western blot or immunohistochemistry. Tissue level of superoxide anion (O2·-) in RVLM was determined using the oxidation-sensitive fluorescent probe dihydroethidium. Pharmacological agents were delivered either via infusion into the cisterna magna with an osmotic minipump or microinjection bilaterally into RVLM. Results Intraperitoneal infusion of LPS (1.2?mg/kg/day) for 14?days promoted sustained hypertension and induced a significant increase in plasma level of C-reactive protein, tumor necrosis factor-? (TNF-?), or interleukin-1? (IL-1?). This LPS-induced systemic inflammation was accompanied by activation of microglia, augmentation of IL-1?, IL-6, or TNF-? protein expression, and O2·- production in RVLM, all of which were blunted by intracisternal infusion of a cycloxygenase-2 (COX-2) inhibitor, NS398; an inhibitor of microglial activation, minocycline; or a cytokine synthesis inhibitor, pentoxifylline. Neuroinflammation in RVLM was also associated with a COX-2-dependent downregulation of endothelial nitric oxide synthase and an upregulation of intercellular adhesion molecule-1. Finally, the LPS-promoted long-term pressor response and the reduction in expression of voltage-gated potassium channel, Kv4.3 in RVLM were antagonized by minocycline, NS398, pentoxifylline, or a superoxide dismutase mimetic, tempol, either infused into cisterna magna or microinjected bilaterally into RVLM. The same treatments, on the other hand, were ineffective against LPS-induced systemic inflammation. Conclusion These results suggest that systemic inflammation activates microglia in RVLM to induce COX-2-dependent neuroinflammation that leads to an increase in O2·- production. The resultant oxidative stress in RVLM in turn mediates neurogenic hypertension.

2012-01-01

179

The iron chelator pyridoxal isonicotinoyl hydrazone (PIH) protects plasmid pUC18 DNA against OH-mediated strand breaks  

Microsoft Academic Search

Pyridoxal isonicotinoyl hydrazone (PIH) has previously been studied for use in iron chelation therapy in iron-overload diseases. It is an efficient in vitro antioxidant due to its Fe(III) complexing activity (Schulman, H. M., et al. Redox Report1:373–378; 1995). Pathologies associated with iron-overload include hepatic and other cancers. Since oxidative alterations of DNA can be linked to the development of cancer,

Marcelo Hermes-Lima; Eva Nagy; Prem Ponka; Herbert M Schulman

1998-01-01

180

Lack of Bcr and Abr Promotes Hypoxia-Induced Pulmonary Hypertension in Mice  

PubMed Central

Background Bcr and Abr are GTPase activating proteins that specifically downregulate activity of the small GTPase Rac in restricted cell types in vivo. Rac1 is expressed in smooth muscle cells, a critical cell type involved in the pathogenesis of pulmonary hypertension. The molecular mechanisms that underlie hypoxia-associated pulmonary hypertension are not well-defined. Methodology/Principal Findings Bcr and abr null mutant mice were compared to wild type controls for the development of pulmonary hypertension after exposure to hypoxia. Also, pulmonary arterial smooth muscle cells from those mice were cultured in hypoxia and examined for proliferation, p38 activation and IL-6 production. Mice lacking Bcr or Abr exposed to hypoxia developed increased right ventricular pressure, hypertrophy and pulmonary vascular remodeling. Perivascular leukocyte infiltration in the lungs was increased, and under hypoxia bcr?/? and abr?/? macrophages generated more reactive oxygen species. Consistent with a contribution of inflammation and oxidative stress in pulmonary hypertension-associated vascular damage, Bcr and Abr-deficient animals showed elevated endothelial leakage after hypoxia exposure. Hypoxia-treated pulmonary arterial smooth muscle cells from Bcr- or Abr-deficient mice also proliferated faster than those of wild type mice. Moreover, activated Rac1, phosphorylated p38 and interleukin 6 were increased in these cells in the absence of Bcr or Abr. Inhibition of Rac1 activation with Z62954982, a novel Rac inhibitor, decreased proliferation, p38 phosphorylation and IL-6 levels in pulmonary arterial smooth muscle cells exposed to hypoxia. Conclusions Bcr and Abr play a critical role in down-regulating hypoxia-induced pulmonary hypertension by deactivating Rac1 and, through this, reducing both oxidative stress generated by leukocytes as well as p38 phosphorylation, IL-6 production and proliferation of pulmonary arterial smooth muscle cells.

Lim, Min; Arutyunyan, Anna; Groffen, John; Heisterkamp, Nora

2012-01-01

181

Attenuation of Angiotensin II-induced Vascular Dysfunction and Hypertension by Overexpression of Thioredoxin-2  

PubMed Central

Reactive oxygen species (ROS) increase in the cardiovascular system during hypertension and in response to angiotensin II. As mitochondria contribute to ROS-generation we sought to investigate the role of thioredoxin-2, a mitochondria specific antioxidant enzyme. Mice were created with overexpression of human thioredoxin-2 (TghTrx2 mice) and backcrossed to C57BL/6J mice for at least 6 generations. 12 week old male TghTrx2 or littermate wild-type mice were made hypertensive by infusion of angiotensin II (400ng/kg per min) for 14 days using osmotic minipumps. Systolic arterial blood pressure was not different between TghTrx2 and wild-type animals under baseline conditions (101±1 resp. 102±1 mmHg). The angiotensin II-induced hypertension in wild-type (145±2 mmHg) was significantly attenuated in TghTrx2 mice (124±1 mmHg, p<0.001). Aortic endothelium-dependent relaxation was significantly reduced in wild-type following angiotensin II infusion, but nearly unchanged in transgenic mice. Elevated vascular superoxide and hydrogen peroxide levels as well as expression of NADPH oxidase subunits in response to angiotensin II infusion were significantly attenuated in TghTrx2 mice. Mitochondrial superoxide anion levels were augmented after angiotensin II infusion in wild-type mice, this was blunted in TghTrx2 mice. Angiotensin II infusion significantly increased myocardial superoxide formation, heart weight and cardiomyocyte size in wild-type, but not in TghTrx2 mice. These data indicate a major role for mitochondrial thioredoxin-2 in the development of cardiovascular alterations and hypertension during chronic angiotensin II infusion. Thioredoxin-2 may represent an important therapeutic target for the prevention and treatment of hypertension and oxidative stress.

Widder, Julian D.; Fraccarollo, Daniela; Galuppo, Paolo; Hansen, Jason M.; Jones, Dean P.; Ertl, Georg; Bauersachs, Johann

2009-01-01

182

Vasopressin-induced calcium increases in smooth muscle cells from spontaneously hypertensive rats.  

PubMed

Cytosolic free Ca2+ concentrations [( Ca2+]i) were measured in smooth muscle cells (SMC) from spontaneously hypertensive rats (SHR) and age and sex matched Wistar-Kyoto rats (WKY). Resting levels of [Ca2+]i were 114 +/- 6 nM and 116 +/- 5 nM in SMC from WKY and SHR, respectively. Angiotensin II (AII) induced a dose-dependent large increases in [Ca2+]i in SMC. There were no significant differences in resting or AII-stimulated levels of [Ca2+]i when SMC from WKY and SHR were compared. Arg-vasopressin (AVP) caused a similar but smaller [Ca2+]i increase than AII in SMC. AVP caused larger [Ca2+]i increases in SMC from SHR than in SMC from WKY. Although concentrations of AVP higher than those ordinarily detected in plasma were necessary to obtain different responses between SHR and WKY, these differences may be related to the pathogenesis of hypertension. PMID:4021731

Nabika, T; Velletri, P A; Beaven, M A; Endo, J; Lovenberg, W

1985-08-12

183

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

PubMed

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 Ca(2+) 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 Ca(2+) 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 Ca(2+)-ATPase activity, increased sarcoplasmic reticular Ca(2+)-release fraction, and increased Ca(2+) 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 Ca(2+) 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

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; White, Ed

2012-03-16

184

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

PubMed Central

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.

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

185

Therapeutic potential of nitric oxide donors in the prevention and treatment of angiogenesis-inhibitor-induced hypertension.  

PubMed

Angiogenesis is critical to tumor growth as well as to metastases. This process is tightly regulated by pro- and anti-angiogenic growth factors and their receptors. Some of these factors are highly specific for the endothelium-e.g., vascular endothelial growth factor (VEGF). A variety of drugs that target VEGF or its receptors have been developed for the treatment of different tumor types and a number of new agents is expected to be introduced within the coming years. However, clinical experience has revealed that inhibition of VEGF induces several side effects including hypertension and renal and cardiac toxicity. Angiogenesis-inhibitor-induced hypertension represents "crux medicorum" as it is often pharmacoresistant to antihypertensive therapy. We consider two most important pathomechanisms in the development of hypertension induced by angiogenesis inhibitors. The first represents direct inhibition of NO production leading to reduced vasodilatation and the second consists in increased proliferation of vascular medial cells mediated by NO deficiency and is resulting in fixation of hypertension. Based on the results of experimental and clinical studies as well as on our clinical experience, we assume that NO donors could be successfully used not only for the treatment of developed angiogenesis-inhibitor-induced hypertension but also for preventive effects. We thoroughly documented three clinical cases of cancer patients with resistant hypertension who on receiving NO donor treatment achieved target blood pressure level and a good clinical status. PMID:23203441

Kruzliak, Peter; Kovacova, Gabriela; Pechanova, Olga

2012-12-01

186

Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension.  

PubMed

We recently found that adipose afferent reflex (AAR) induced by chemical stimulation of white adipose tissue (WAT) increased sympathetic outflow and blood pressure in normal rats. The study was designed to test the hypothesis that AAR contributes to sympathetic activation in obesity hypertension. Male rats were fed with a control diet (12% kcal as fat) or high-fat diet (42% kcal as fat) for 12 weeks to induce obesity hypertension. Stimulation of WAT with capsaicin increased renal sympathetic nerve activity and mean arterial pressure. Both AAR and WAT afferent activity were enhanced in obesity hypertension (OH) compared with obesity nonhypertension (ON) and in ON compared with obesity-resistant or control diet rats. WAT sensory denervation induced by resiniferatoxin caused greater decreases in renal sympathetic nerve activity and mean arterial pressure in OH than ON and in ON than obesity-resistant or control. The depressor effect of resiniferatoxin lasted ? 3 weeks in OH. Leptin antagonist in WAT reduced renal sympathetic nerve activity and mean arterial pressure in OH. WAT injection of capsaicin increased plasma renin, angiotensin II, and norepinephrine levels in OH and caused more c-fos expression in paraventricular nucleus in OH than ON and in ON than obesity-resistant or control rats. Inhibiting paraventricular nucleus neurons with lidocaine attenuated renal sympathetic nerve activity in OH and ON, decreased mean arterial pressure in OH, and abolished the capsaicin-induced AAR in all groups. The results indicate that enhanced AAR contributes to sympathetic activation in OH, and paraventricular nucleus plays an important role in the enhanced AAR and sympathetic activation in OH. PMID:23033372

Xiong, Xiao-Qing; Chen, Wei-Wei; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing

2012-10-01

187

[Hypertension and pregnancy. Diagnosis, physiopathology and treatment].  

PubMed

This review on hypertension in pregnancy focuses mainly on the pathophysiology and prevention of pregnancy induced hypertension which, when associated with proteinuria, is usually called preeclampsia. Rather than a genuine hypertensive disease, preeclampsia is mainly a systemic endothelial disease causing activation of platelets and diffuse ischemic disorders whose most obvious clinical manifestations involve the kidney (hence the proteinuria, edema and hyperuricemia), the liver (hence the hemolytic elevated liver enzymes and low platelets, or HELLP syndrome), and the brain (hence eclamptic convulsions). Hypertension is explained by increased vascular reactivity rather than by an imbalance between vasoconstrictive and vasodilating circulating hormones. This increased reactivity is due to endothelial dysfunction with imbalance between prostacyclin and thromboxane A2 and possibly dysfunction of NO and endothelin synthesis. The aggressive substances for endothelium are thought to be of placentar origin and the cause of their release is explained by placentar ischemia related to a defect of trophoblastic invasion of the spiral arteries. The etiology of this latter defect is unknown but involves immunologic mechanisms with genetic predisposition. The only effective treatment for PIH is extraction of the baby with the whole placenta. The decision for extraction is often a very delicate obstetric problem. Antihypertensive drugs are mainly indicated in severe hypertension (> 160-100 mm Hg), with the aim of preventing cerebral hemorrhage in the mother, but have not been shown to improve fetal morbidity or mortality. Eclamptic seizures can be prevented and treated more effectively with magnesium sulfate than with diazepam or phenytoin. Prevention of preeclampsia remains the main challenge. Whereas antihypertensive drugs are ineffective, calcium supplementation and low dose aspirin have proven effective but mainly in selected populations with a relatively high incidence of preeclampsia (> 8-10%). In multiparas the selection of such a high risk population is relatively easy when at least 2 (or 1?) previous pregnancies were complicated with early preeclampsia and/or intrauterine growth retardation. In nulliparas the selection of the high-risk population is still a subject of research. The 2 most promising criteria are abnormal Doppler velocimetry of the uterine arteries at around 20 weeks of amenorrhea, and abnormally high plasma levels of beta HCG at 17 weeks of amenorrhea. PMID:8539576

Fournier, A; Fievet, P; el Esper, I; el Esper, N; Vaillant, P; Gondry, J

1995-11-25

188

Leptin and interferon-gamma as possible predictors of cesarean section among women with hypertensive disorders of pregnancy  

PubMed Central

Summary Background This study was designed to evaluate maternal levels of leptin and interferon-gamma (IFN-gamma) in pregnancy complicated with hypertension and to assess the role of cytokines in predicting the risk of cesarean section. Material/Methods This was a cohort study with a prospective follow-up. After proportional sampling procedure, the study included the follow-up of 40 women with hypertensive disorders of pregnancy (pregnancy-induced hypertension [PIH] or preeclampsia [PE]) and 40 uncomplicated pregnancies. Women were followed from the time of admission to the delivery. Levels of leptin and interferon-gamma were measured in serum samples from all women. A p-value <0.05 was considered as significant. Results Significant increase in IFN-gamma and leptin concentration in women with pre-eclampsia was observed. We found a significant 1.4-fold increase in the risk of birth by cesarean section associated with the increase of the IFN-gamma concentration by 0.1 pg/ml and almost 3-fold increase in the risk associated with the increase of the leptin concentration. Conclusions IFN-? and leptin might be risk markers of cesarean section in hypertension disorders of pregnancy, but further studies supporting this evidence are needed.

Rytlewski, Krzysztof; Huras, Hubert; Kusmierska-Urban, Katarzyna; Galas, Aleksander; Reron, Alfred

2012-01-01

189

Effect of simvastatin on remodeling of the left ventricle and aorta in L-NAME-induced hypertension  

Microsoft Academic Search

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been shown to prevent or reverse hypertrophy of the LV in several models of left ventricular hypertrophy. The aim of the present study was to determine whether treatment with simvastatin can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) remodeling in NG-nitro–L-arginine methyl ester(L-NAME)-induced hypertension. Four groups of

Fedor Simko; Jana Matuskova; Ivan Luptak; Kristina Krajcirovicova; Jarmila Kucharska; Anna Gvozdjakova; Pavel Babal; Olga Pechanova

2004-01-01

190

Hypertension Augments Ethanol-Induced Depression of Cell Shortening and Intracellular Ca 2+ Transients in Adult Rat Ventricular Myocytes  

Microsoft Academic Search

Ethanol, a risk factor for myocardial dysfunction, depresses myocardial contraction. This study was to determine whether ethanol-induced myocardial depression is affected by hypertension. Mechanical properties of ventricular myocytes isolated from both normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats were evaluated using a video edge-detection system. Myocytes were electrically stimulated to contract at 0.5 Hz. Contractile properties analyzed include peak

Jun Ren; Ricardo A. Brown

1999-01-01

191

Glucocorticoid-Induced Hypertension and Tetrahydrobiopterin (BH4), a Common Cofactor for the Production of Vasoactive Molecules  

Microsoft Academic Search

Excess glucocorticoids, whether produced endogenously or over-prescrib ed for immunosupression and anti- inflammation, can lead to hypertension and cardiovascular disease. Humans and animals with glucocorticoid-induced hypertension exhibit reduced nitric oxide (NO) and serotonin, and have increased sensitivity to catecholamine s. The common cofactor for the production of these vasoactive molecules is tetrahydrobio pterin (BH4). Recent research has focused on the

Brett M. Mitchell; Clinton Webb

2005-01-01

192

Syringic acid ameliorates (L)-NAME-induced hypertension by reducing oxidative stress.  

PubMed

The objective of the present study was to investigate the effects of syringic acid (SA), a phenolic acid, on N(?)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Hypertension was induced in adult male albino rats by oral administration of L-NAME (40 mg/kg/day) dissolved in drinking water daily for 4 weeks. Rats were treated with different doses of SA (25, 50, and 100 mg/kg body weight (b.w.)). Systolic blood pressure of control and experimental rats was recorded. Plasma nitric oxide metabolites (NOx), lipid peroxidative products such as thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes, and antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, vitamin C, vitamin E, and reduced glutathione were estimated in erythrocytes, plasma, and tissues of experimental rats. Hepatic marker enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase and renal functional markers such as urea, uric acid, and creatinine were also estimated in serum. The increased levels of blood pressure, lipid peroxidation products, hepatic and renal function markers, and the decreased level of NOx and antioxidants in L-NAME-induced hypertensive rats were reversed upon SA treatment. The protective effect at the dose of the three tested doses (25, 50, and 100 mg/kg) of SA at a dose of 50 mg/kg b.w. exerts optimum protection. Biochemical findings are substantiated by the histological observation. The protective effects of SA are mediated by reducing oxidative stress and retaining the bioavailability of NO in the cardiovascular system. PMID:23079793

Kumar, Subramanian; Prahalathan, Pichavaram; Raja, Boobalan

2012-10-19

193

Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension  

PubMed Central

Glucocorticoid-mediated hypertension is incompletely understood. Recent studies have suggested the primary mechanism of this form of hypertension may be through the effects of glucocorticoids on vascular tissues and not to excess sodium and water reabsorption as traditionally believed. Objective The goal of this study was to better understand the role of the vasculature in the generation and maintenance of glucocorticoid-mediated hypertension. Methods We created a mouse model with a tissue-specific knockout of the glucocorticoid receptor in the vascular endothelium. Results We show that these mice are relatively resistant to dexamethasone-induced hypertension. After one week of dexamethasone treatment, control animals have a mean blood pressure increase of 13.1 mm Hg while knockout animals have only a 2.7 mm Hg increase (p<0.001). Interestingly, the knockout mice have slightly elevated baseline BP compared to the controls (112.2 ± 2.5 mm Hg vs. 104.6 ± 1.2 mm Hg, p = 0.04), a finding which is not entirely explained by our data. Furthermore, we demonstrate that the knockout resistance arterioles have a decreased contractile response to dexamethasone with only 6.6% contraction in knockout vessels compared to 13.4% contraction in control vessels (p=0.034). Finally, we show that in contrast to control animals, the knockout animals are able to recover a significant portion of their normal circadian blood pressure rhythm suggesting that the vascular endothelial glucocorticoid receptor may function as a peripheral circadian clock. Conclusions Our study highlights the importance of the vascular endothelial GR in several fundamental physiologic processes, namely blood pressure homeostasis and circadian rhythm.

GOODWIN, Julie E.; ZHANG, Junhui; GONZALEZ, David; ALBINSSON, Sebastian; GELLER, David S.

2012-01-01

194

Hydrogen Sulfide Attenuates Carbon Tetrachloride-Induced Hepatotoxicity, Liver Cirrhosis and Portal Hypertension in Rats  

Microsoft Academic Search

BackgroundHydrogen sulfide (H2S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. Impaired production of H2S contributes to the increased intrahepatic resistance in cirrhotic livers. The study aimed to investigate the roles of H2S in carbon tetrachloride (CCl4)-induced hepatotoxicity, cirrhosis and portal hypertension.Methods and FindingsSodium hydrosulfide (NaHS), a donor of H2S, and DL-propargylglycine (PAG), an irreversible inhibitor of cystathionine ?-lyase (CSE), were

Gang Tan; Shangha Pan; Jie Li; Xuesong Dong; Kai Kang; Mingyan Zhao; Xian Jiang; Jagat R. Kanwar; Haiquan Qiao; Hongchi Jiang; Xueying Sun; Antonio Bertoletti

2011-01-01

195

Facilitation by beta-adrenoreceptors of stimulation-induced vasoconstriction in pithed spontaneously hypertensive rats.  

PubMed

In pithed bilateral adrenal demedullated spontaneously hypertensive rats, slow i.v. infusion of adrenaline (500 ng/min) significantly increased pressor responses to the electrical stimulation of the entire sympathetic outflow, but had little effect on pressor responses induced by bolus injections of noradrenaline. After pretreatment with timolol (1 mg/kg, i.v., 30 min) adrenaline infusion enhanced noradrenaline-induced pressor effects, but not stimulation-induced responses. Salbutamol (50-500 ng/min, i.v.) and procaterol (2.5 ng/min, i.v.) infusions significantly potentiated stimulation-induced pressor effects without affecting noradrenaline-induced responses. Higher rates of salbutamol (5 micrograms/min, i.v.) and procaterol (25 ng/min, i.v.) infusion significantly depressed noradrenaline-induced pressor effects and attenuated those induced by sympathetic nerve stimulation. It is concluded that the potentiation of stimulation-induced pressor responses by adrenaline salbutamol and procaterol, involves a beta-adrenoreceptor mediated facilitation of sympathetic neurotransmission. PMID:6146623

Borkowski, K R; Quinn, P

1984-06-01

196

Sarcoidosis-induced pericarditis in a patient with portopulmonary hypertension: a case report  

Microsoft Academic Search

Portopulmonary hypertension is a rare and severe complication of patients with cirrhosis. Sarcoidosis, a disease of unknown etiology, is also a cause of pulonary hypertension and right heart dysfunction. We report the case of a 51-year-old male patient, suffering from cirrhosis due to Wilson's disease, portal hypertension and pulmonary hypertension (PH), who developed severe pericarditis. Wilson's disease was diagnosed 8

Olga Giouleme; Panagiotis Anagnostis; Kalliopi Patsiaoura; Themistoklis Vasiliadis; Nikolaos Grammatikos; Nikitas Kakavas; Alexander Mpoumponaris; Nikolaos Eugenidis; Elias Basayannis

2009-01-01

197

20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension.  

PubMed

20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P-450 (Cyp)-derived arachidonic acid metabolite that has been shown to increase smooth muscle contractions and proliferation, stimulate endothelial dysfunction and activation, and promote hypertension. We examined if 20-HETE contributes to microvascular remodeling in hypertension. In Sprague-Dawley rats, administration of the 20-HETE biosynthesis inhibitor HET0016 or the 20-HETE antagonist N-20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) prevented 5?-dihydrotestosterone (DHT)-induced increases in blood pressure as well as abrogated DHT-induced increases in the media-to-lumen ratio (M/L), media thickness, and collagen IV deposition in renal interlobar arteries. Reserpine prevented blood pressure elevation in DHT-treated rats but did not affect microvascular remodeling (M/L, media thickness, and collagen deposition); under these conditions, treatment with the 20-HETE antagonist attenuated microvascular remodeling, suggesting that 20-HETE contributes to DHT-induced vascular remodeling independent of blood pressure elevation. In Cyp4a14(-/-) mice, which display androgen-driven and 20-HETE-dependent hypertension, treatment with the 20-HETE antagonist abolished remodeling of renal resistance arteries measured as media thickness (24 ± 1 vs. 15 ± 1 ?m) and M/L (0.29 ± 0.03 vs. 0.17 ± 0.01). Moreover, in Cyp4a12 transgenic mice in which the expression of Cyp4a12-20-HETE synthase is driven by a tetracycline-sensitive promoter, treatment with doxycycline resulted in blood pressure elevation (140 ± 4 vs. 92 ± 5 mmHg) and a significant increase in remodeling of renal resistance arteries (media thickness: 23 ± 1 vs. 16 ± 1 ?m; M/L: 0.39 ± 0.04 vs. 0.23 ± 0.02); these increases were abrogated by cotreatment with 20-HEDE. This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. PMID:23825080

Ding, Yan; Wu, Cheng-Chia; Garcia, Victor; Dimitrova, Irina; Weidenhammer, Adam; Joseph, Gregory; Zhang, Frank; Manthati, Vijay L; Falck, John R; Capdevila, Jorge H; Schwartzman, Michal L

2013-07-03

198

Acute exercise exacerbates ischemia-induced diastolic rigor in hypertensive myocardium.  

PubMed

Previous studies have shown that acute exercise preconditions the myocardium from ischemic injury. The purpose of this study was to test whether acute exercise protects the hypertensive myocardium from ischemia-induced diastolic rigor, and to compare the response between normotensive and uncompensated hypertensive hearts. Hearts harvested from female Wistar-Kyoto (WKY; n = 24) and spontaneously hypertensive rats (SHR; n = 27) (age:10-12 weeks) were exposed to ischemia (Langendorff isovolumic preparation; 22 minutes of no flow ischemia and studied following prior conditions of: 1) no exercise (WKY-CON, n=8; SHR-CON, n=8); 2) ischemia initiated one hour post-acute exercise (WKY-1HR, n = 8; SHR-1HR, n = 11); and 3) ischemia initiated 24 hours post-acute exercise (WKY-24HR; n = 8; SHR-24HR, n = 8). Acute exercise consisted of one bout of treadmill running at 25 m/min for 60 minutes. Heart weight was similar between WKY and SHR despite elevated in vivo resting systolic blood pressure and rate pressure product in SHR (P<0.05). During normoxic perfusion, left ventricular (LV) Langendorff performance was similar between WKY and SHR over the post-exercise time course. However, during ischemia, LV diastolic rigor was less in WKY vs. SHR (P<0.05). Acute exercise augmented ischemia-induced LV dysfunction one hour post-exercise in SHR (P<0.05), with gradual recovery by 24 hours post-exercise. These data suggest that acute exercise promotes ischemic diastolic rigor in SHR, even prior to the development of cardiac hypertrophy. PMID:23961371

Reger, Patricia O; Kolwicz, Stephen C; Libonati, Joseph R

2012-11-02

199

SPIRONOLACTONE PREVENTS CHLORTHALIDONE-INDUCED SYMPATHETIC ACTIVATION AND INSULIN RESISTANCE IN HYPERTENSIVE PATIENTS  

PubMed Central

Recent studies from our laboratory indicate that chlorthalidone triggers persistent activation of the sympathetic nervous system and promotes insulin resistance in hypertensive patients, independent of serum potassium. Mechanisms underlying these adverse effects of chlorthalidone remain unknown but increasing evidence in rodents suggests the role of angiotensin and aldosterone excess in inducing both sympathetic overactivity and insulin resistance. Accordingly, we conducted studies in 17 subjects with untreated stage I hypertension, measuring sympathetic nerve activity (SNA) at baseline, after 12 weeks of chlorthalidone alone (25 mg/day), chlorthalidone plus spironolactone, and chlorthalidone plus irbesartan, using randomized crossover design. We found that chlorthalidone alone decreased 24-hour ambulatory BP (ABP) from 135±3/84±2 to 124±2/78±2 mm Hg and significantly increased SNA from baseline (from 41±3 vs 49±4 bursts/min, p < 0.01). Addition of spironolactone to chlorthalidone returned SNA value to baseline (42±3 bursts/min, p = NS) while addition of irbesartan failed to alter the SNA response to chlorthalidone in the same subjects (52±2 bursts/min, p < 0.01) despite similar reduction in ABP (121±2/75±2 and 121±2/75±2 mmHg, respectively). Chlorthalidone alone also increased indices of insulin resistance, which was not observed when used in combination with spironolactone. In conclusion, our study demonstrates beneficial effects of spironolactone in attenuating both chlorthalidone-induced sympathetic activation and insulin resistance in humans, independent of BP reduction. Because sympathetic overactivity and insulin resistance contributes to the poor prognosis in patients with cardiovascular disease, combination therapy of chlorthalidone with mineralocorticoid receptor antagonists may constitute a preferable regimen than chlorthalidone alone in hypertensive patients.

Raheja, Prafull; Price, Angela; Wang, Zhongyun; Arbique, Debbie; Adams-Huet, Beverley; Auchus, Richard J.; Vongpatanasin, Wanpen

2012-01-01

200

Is gender crucial for cardiovascular adjustments induced by exercise training in female spontaneously hypertensive rats?  

PubMed

Evidence of mild hypertension in women and female rats and our preliminary observation showing that training is not effective to reduce pressure in female as it does in male spontaneously hypertensive rats (SHR) prompt us to investigate the effects of gender on hemodynamic pattern and microcirculatory changes induced by exercise training. Female SHR and normotensive controls (Wistar-Kyoto rats) were submitted to training (55% VO(2) peak; 3 months) or kept sedentary and instrumented for pressure and hindlimb flow measurements at rest and during exercise. Heart, kidney, and skeletal muscles (locomotor/nonlocomotor) were processed for morphometric analysis of arterioles, capillaries, and venules. High pressure in female SHR was accompanied by an increased arteriolar wall:lumen ratio in the kidney (+30%; P<0.01) but an unchanged ratio in the skeletal muscles and myocardium. Female SHR submitted to training did not exhibit further changes on the arteriolar wall:lumen ratio and pressure, showing additionally increased hindlimb resistance at rest (+29%; P<0.05). On the other hand, female SHR submitted to training exhibited increased capillary and venular densities in locomotor muscles (+50% and 2.3-fold versus sedentary SHR, respectively) and normalized hindlimb flow during exercise hyperemia. Left ventricle pressure and weight were higher in SHR versus WKY rats, but heart performance (positive dP/dt(max) and negative dP/dt(max)) was not changed by hypertension or training, suggesting a compensated heart function in female SHR. In conclusion, the absence of training-induced structural changes on skeletal muscle and myocardium arterioles differed from changes observed previously in male SHR, suggesting a gender effect. This effect might contribute to the lack of pressure fall in trained female SHRs. PMID:18695147

Coimbra, Rosemeire; Sanchez, Lylian S; Potenza, Janaina M; Rossoni, Luciana V; Amaral, Sandra Lia; Michelini, Lisete C

2008-08-11

201

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

PubMed

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

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

2012-10-07

202

Spironolactone prevents chlorthalidone-induced sympathetic activation and insulin resistance in hypertensive patients.  

PubMed

Recent studies from our laboratory indicate that chlorthalidone triggers persistent activation of the sympathetic nervous system and promotes insulin resistance in hypertensive patients, independent of serum potassium. Mechanisms underlying these adverse effects of chlorthalidone remain unknown, but increasing evidence in rodents suggests the role of angiotensin and aldosterone excess in inducing both sympathetic overactivity and insulin resistance. Accordingly, we conducted studies in 17 subjects with untreated stage 1 hypertension, measuring sympathetic nerve activity at baseline and after 12 weeks of chlorthalidone alone (25 mg/d), chlorthalidone plus spironolactone, and chlorthalidone plus irbesartan, using randomized crossover design. We found that chlorthalidone alone decreased 24-hour ambulatory blood pressure from 135±3/84±2 to 124±2/78±2 mm Hg and significantly increased sympathetic nerve activity from baseline (from 41±3 versus 49±4 bursts per minute; P<0.01). The addition of spironolactone to chlorthalidone returned sympathetic nerve activity value to baseline (42±3 bursts per minute; P>0.05), whereas the addition of irbesartan failed to alter the sympathetic nerve activity response to chlorthalidone in the same subjects (52±2 bursts per minute; P<0.01) despite a similar reduction in ambulatory blood pressure (121±2/75±2 and 121±2/75±2 mm Hg, respectively). Chlorthalidone alone also increased indices of insulin resistance, which was not observed when used in combination with spironolactone. In conclusion, our study demonstrates beneficial effects of spironolactone in attenuating both chlorthalidone-induced sympathetic activation and insulin resistance in humans, independent of blood pressure reduction. Because sympathetic overactivity and insulin resistance contribute to the poor prognosis in patients with cardiovascular disease, combination therapy of chlorthalidone with mineralocorticoid receptor antagonists may constitute a preferable regimen than chlorthalidone alone in hypertensive patients. PMID:22733474

Raheja, Prafull; Price, Angela; Wang, Zhongyun; Arbique, Debbie; Adams-Huet, Beverley; Auchus, Richard J; Vongpatanasin, Wanpen

2012-06-25

203

Inhibition of TNF in the Brain Reverses Alterations in RAS Components and Attenuates Angiotensin II-Induced Hypertension  

PubMed Central

Dysfunction of brain renin-angiotensin system (RAS) components is implicated in the development of hypertension. We previously showed that angiotensin (Ang) II-induced hypertension is mediated by increased production of proinflammatory cytokines (PIC), including tumor necrosis factor (TNF), in brain cardiovascular regulatory centers such as the paraventricular nucleus (PVN). Presently, we tested the hypothesis that central TNF blockade prevents dysregulation of brain RAS components and attenuates Ang II-induced hypertension. Male Sprague-Dawley rats were implanted with radio-telemetry transmitters to measure mean arterial pressure (MAP) and subjected to intracerebroventricular (ICV) infusion of etanercept (10 µg/kg/day) with/without concurrent subcutaneous 4-week Ang II (200 ng/kg/min) infusion. Chronic Ang II infusion resulted in a significant increase in MAP and cardiac hypertrophy, which was attenuated by inhibition of brain TNF with etanercept. Etanercept treatment also attenuated Ang II-induced increases in PIC and decreases in IL-10 expression in the PVN. Additionally, Ang II infusion increased expression of pro-hypertensive RAS components (ACE and AT1R), while decreasing anti-hypertensive RAS components (ACE2, Mas, and AT2 receptors), within the PVN. ICV etanercept treatment reversed these changes. Ang II-infusion was associated with increased oxidative stress as indicated by increased NAD(P)H oxidase activity and super oxide production in the PVN, which was prevented by inhibition of TNF. Moreover, brain targeted TNF blockade significantly reduced Ang II-induced NOX-2 and NOX-4 mRNA and protein expression in the PVN. These findings suggest that chronic TNF blockade in the brain protects rats against Ang II-dependent hypertension and cardiac hypertrophy by restoring the balance between pro- and anti-hypertensive RAS axes and inhibiting PIC and oxidative stress genes and proteins in the PVN.

Sriramula, Srinivas; Cardinale, Jeffrey P.; Francis, Joseph

2013-01-01

204

Inhibition of TNF in the brain reverses alterations in RAS components and attenuates angiotensin II-induced hypertension.  

PubMed

Dysfunction of brain renin-angiotensin system (RAS) components is implicated in the development of hypertension. We previously showed that angiotensin (Ang) II-induced hypertension is mediated by increased production of proinflammatory cytokines (PIC), including tumor necrosis factor (TNF), in brain cardiovascular regulatory centers such as the paraventricular nucleus (PVN). Presently, we tested the hypothesis that central TNF blockade prevents dysregulation of brain RAS components and attenuates Ang II-induced hypertension. Male Sprague-Dawley rats were implanted with radio-telemetry transmitters to measure mean arterial pressure (MAP) and subjected to intracerebroventricular (i.c.v.) infusion of etanercept (10 µg/kg/day) with/without concurrent subcutaneous 4-week Ang II (200 ng/kg/min) infusion. Chronic Ang II infusion resulted in a significant increase in MAP and cardiac hypertrophy, which was attenuated by inhibition of brain TNF with etanercept. Etanercept treatment also attenuated Ang II-induced increases in PIC and decreases in IL-10 expression in the PVN. Additionally, Ang II infusion increased expression of pro-hypertensive RAS components (ACE and AT1R), while decreasing anti-hypertensive RAS components (ACE2, Mas, and AT2 receptors), within the PVN. I.c.v. etanercept treatment reversed these changes. Ang II-infusion was associated with increased oxidative stress as indicated by increased NAD(P)H oxidase activity and super oxide production in the PVN, which was prevented by inhibition of TNF. Moreover, brain targeted TNF blockade significantly reduced Ang II-induced NOX-2 and NOX-4 mRNA and protein expression in the PVN. These findings suggest that chronic TNF blockade in the brain protects rats against Ang II-dependent hypertension and cardiac hypertrophy by restoring the balance between pro- and anti-hypertensive RAS axes and inhibiting PIC and oxidative stress genes and proteins in the PVN. PMID:23691105

Sriramula, Srinivas; Cardinale, Jeffrey P; Francis, Joseph

2013-05-15

205

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

SciTech Connect

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.

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

1990-08-01

206

Severe pulmonary arterial hypertension induced by SU5416 and ovalbumin immunization.  

PubMed

The combination of chronic hypoxia and treatment of rats with the vascular endothelial growth factor (VEGF) receptor blocker, SU5416, induces pulmonary angio-obliteration, resulting in severe pulmonary arterial hypertension (PAH). Inflammation is thought to contribute to the pathology of PAH. Allergic inflammation caused by ovalbumin (OVA) immunization causes muscularization of pulmonary arteries, but not severe PAH. Whether disturbance of the immune system and allergic inflammation in the setting of lung endothelial cell apoptosis causes PAH is unknown. We investigated the effects of OVA-allergic inflammation on the development of PAH initiated by VEGF blockade-induced lung endothelial cell apoptosis. OVA-immunized rats were treated with SU5416 to induce pulmonary vascular endothelial cell apoptosis. The combination of OVA and SU5416 treatment resulted in severe angio-obilterative PAH, accompanied by increased IL-6 expression in the lungs. c-Kit(+) and Sca-1(+) cells were found in and around the lung vascular lesions. Pan-caspase inhibiton, dexamethasone treatment, and depletion of B-lymphocytes using an anti-CD20 antibody suppressed this remodeling. OVA immunization also increased lung tissue hypoxia-induced factor-1? and VEGF expression. Our results also suggest that the increased expression of hypoxia-induced factor-1? and IL-6 induced by the allergic lung inflammation may be a component of the pathogenesis of PAH. PMID:22842496

Mizuno, Shiro; Farkas, Laszlo; Al Husseini, Aysar; Farkas, Daniela; Gomez-Arroyo, Jose; Kraskauskas, Donatas; Nicolls, Mark R; Cool, Carlyne D; Bogaard, Herman J; Voelkel, Norbert F

2012-07-27

207

Dysregulation of PTEN in Cardiopulmonary Vascular Remodeling Induced by Pulmonary Hypertension.  

PubMed

Pulmonary hypertension (PH) is a disorder of lung vasculature characterized by arterial narrowing. Phosphatase-and-tensin homolog on chromosome 10 (PTEN), associated in the progression of multiple cancers, is implicated in arterial remodeling. However, the involvement of PTEN in PH remains unclear. The objective of the present study was to determine the role of PTEN in pulmonary vascular remodeling using established models of PH. The study used rat models of PH, induced by monocrotaline (MCT) administration (60 mg/kg) or continuous hypoxic exposure (10% oxygen) for 3 weeks. Pulmonary artery smooth muscle cells (SMCs) were used for in vitro confirmation. Development of PH was verified by hemodynamic, morphological and histopathology analyses. PTEN and key downstream proteins in pulmonary and cardiac tissues were analyzed by western blotting and RT-PCR. PTEN was significantly decreased (MCT, 53%; Hypoxia, 40%), pAkt was significantly increased (MCT, 42%; Hypoxia, 55%) in tissues of rats with PH. Similar results were observed in SMCs exposed to hypoxia (1% oxygen) for 48 h. Ubiquitination assay showed that PTEN degradation occurs via proteasomal degradation pathway. Western blotting demonstrated a significant downregulation of cell-cycle regulatory proteins p53 and p27, and upregulation of cyclin-D1 in the lungs of both models. The results showed that PTEN-mediated modulation of PI3K pathway was independent of the focal adhesion kinase and fatty acid synthase. The study, for the first time, established that PTEN plays a key role in the progression of pulmonary hypertension. The findings may have potential for the treatment of pulmonary hypertension using PTEN as a target. PMID:22205501

Ravi, Yazhini; Selvendiran, Karuppaiyah; Meduru, Sarath; Citro, Lucas; Naidu, Shan; Khan, Mahmood; Rivera, Brian K; Sai-Sudhakar, Chittoor B; Kuppusamy, Periannan

2013-11-01

208

Complement C3 Deficiency Attenuates Chronic Hypoxia-Induced Pulmonary Hypertension in Mice  

PubMed Central

Background Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension. Methodology/Principal Findings Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3?/? hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3?/? mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3?/? mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3?/? mice. Conclusions Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

Bauer, Eileen M.; Zheng, Han; Comhair, Suzy; Erzurum, Serpil; Billiar, Timothy R.; Bauer, Philip M.

2011-01-01

209

Physical training prevents oxidative stress in L-NAME-induced hypertension rats.  

PubMed

The present study investigated the effects of a 6-week swimming training on blood pressure, nitric oxide (NO) levels and oxidative stress parameters such as protein and lipid oxidation, antioxidant enzyme activity and endogenous non-enzymatic antioxidant content in kidney and circulating fluids, as well as on serum biochemical parameters (cholesterol, triglycerides, urea and creatinine) from N?-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension treated rats. Animals were divided into four groups (n = 10): Control, Exercise, L-NAME and Exercise L-NAME. Results showed that exercise prevented a decrease in NO levels in hypertensive rats (P < 0·05). An increase in protein and lipid oxidation observed in the L-NAME-treated group was reverted by physical training in serum from the Exercise L-NAME group (P < 0·05). A decrease in the catalase (CAT) and superoxide dismutase (SOD) activities in the L-NAME group was observed when compared with normotensive groups (P < 0·05). In kidney, exercise significantly augmented the CAT and SOD activities in the Exercise L-NAME group when compared with the L-NAME group (P < 0·05). There was a decrease in the non-protein thiols (NPSH) levels in the L-NAME-treated group when compared with the normotensive groups (P < 0·05). In the Exercise L-NAME group, there was an increase in NPSH levels when compared with the L-NAME group (P < 0·05). The elevation in serum cholesterol, triglycerides, urea and creatinine levels observed in the L-NAME group were reverted to levels close to normal by exercise in the Exercise L-NAME group (P < 0·05). Exercise training had hypotensive effect, reducing blood pressure in the Exercise L-NAME group (P < 0·05). These findings suggest that physical training could have a protector effect against oxidative damage and renal injury caused by hypertension. PMID:22961602

Cardoso, Andréia Machado; Martins, Caroline Curry; Fiorin, Fernando da Silva; Schmatz, Roberta; Abdalla, Fátima Husein; Gutierres, Jessié; Zanini, Daniela; Fiorenza, Amanda Maino; Stefanello, Naiara; Serres, Jonas Daci da Silva; Carvalho, Fabiano; Castro, Verônica Paiva; Mazzanti, Cinthia Melazzo; Royes, Luiz Fernando Freire; Belló-Klein, Adriane; Goularte, Jeferson Ferraz; Morsch, Vera Maria; Bagatini, Margarete Dulce; Schetinger, Maria Rosa Chitolina

2012-09-07

210

Prevention of salt induced hypertension and fibrosis by angiotensin converting enzyme inhibitors in Dahl S rats  

PubMed Central

Background and purpose: In Dahl S rats, high salt increases activity of the tissue renin-angiotensin-aldosterone system (RAAS) in the CNS, heart and kidneys. Here, we assessed the effects of chronic angiotensin converting enzyme (ACE) inhibition on salt-induced hypertension and cardiovascular and renal hypertrophy and fibrosis, relative to the extent of ACE blockade. Experimental approach: From 4.5 weeks of age, Dahl S rats received either the lipophilic ACE inhibitor trandolapril (1 or 5 mg kg-1 day-1) or the hydrophilic ACE inhibitor lisinopril (10 or 50 mg kg-1 day-1) and a high salt diet was started 0.5 week later. Treatments ended at 9 weeks of age. Key results: High salt diet markedly increased blood pressure (BP), decreased plasma angiotensin II and increased ACE binding densities in brain, heart, aorta and kidneys. Trandolapril and lisinopril prevented 50% of the increase in BP in light and dark period of the day. After the last doses, trandolapril decreased ACE densities by ?80% in brain nuclei and heart and lisinopril by ?60% in the brain and by ?70% in the heart. The two ACE inhibitors prevented right ventricular hypertrophy and attenuated left ventricular hypertrophy but did not affect renal hypertrophy caused by high salt. Both drugs prevented high salt-induced fibrosis in heart, kidney and aorta. Conclusion and implication: As the ACE inhibitors could completely prevent tissue fibrosis and partially prevent tissue hypertrophy and hypertension, the tissue RAAS may play a critical role in salt-induced fibrosis, but a lesser role in the hypertrophy.

Liang, B; Leenen, F H H

2007-01-01

211

Melatonin interactions with blood pressure and vascular function during L-NAME-induced hypertension.  

PubMed

The mechanisms responsible for the antihypertensive effect of melatonin are not completely understood. To elucidate the possible role of the nitric oxide (NO) pathway in the hemodynamic actions of melatonin, the effects of this indolamine on vascular function during hypertension induced by the NO-synthase (NOS) inhibitor, N(omega)-nitro-L-arginine-methyl ester (L-NAME) were investigated. Four groups of male adult Wistar rats were employed: control, L-NAME (40 mg/kg), melatonin (10 mg/kg) and L-NAME + melatonin for 5 wks. Systolic and diastolic blood pressure were measured invasively in the carotid artery. Conjugated dienes concentration (an oxidative load marker), NOS RNA expression and its activity and RNA expression of cyclooxygenase-(COX)-1 and COX-2 were determined in the aorta. Acetylcholine-induced responses and their NO-mediated component were evaluated in femoral and mesenteric artery. Moreover, endothelium-derived constricting factor (EDCF)-dependent vasoconstriction and inner diameter were determined in the femoral artery. Chronic L-NAME treatment induced hypertension, elevated the oxidative load and inhibited NOS activity. Moreover, impaired NO-dependent relaxation, augmented EDCF-constriction, increased COX-2 expression and reduced arterial inner diameter were observed. Melatonin added to L-NAME treatment completely prevented elevation of the oxidative load in the aorta. However, melatonin was not able to prevent NOS activity decline, elevation of COX-2 expression or the impairment of vascular responses (except moderate improvement in relaxation of small mesenteric arteries) and it exerted only slight antihypertensive effect. In conclusion, in addition to the reduction of the oxidative load, the restoration of the NO pathway seems to play an important role in the antihypertensive effect of melatonin. PMID:20041987

Paulis, Ludovit; Pechanova, Olga; Zicha, Josef; Barta, Andrej; Gardlik, Roman; Celec, Peter; Kunes, Jaroslav; Simko, Fedor

2009-12-23

212

Intratracheal Gene Transfer of Adrenomedullin Using Polyplex Nanomicelles Attenuates Monocrotaline-induced Pulmonary Hypertension in Rats  

PubMed Central

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive PAH and right ventricular failure. Despite recent advances in therapeutic approaches using prostanoids, endothelin antagonists, and so on, PAH remains a challenging condition. To develop a novel therapeutic approach, we have established a nonviral gene delivery system of poly(ethylene glycol) (PEG)-based block catiomers, which form a polyplex nanomicelle with a nanoscaled core–shell structure in the presence of DNA. The polyplex nanomicelle from PEG-b-poly{N-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-b-P[Asp(DET)]), having ethylenediamine units at the side chain, showed ~100-fold increase in luciferase transgene expression activity in mouse lung via intratracheal administration with a minimal toxicity compared with the polyplex from linear poly(ethylenimine) (LPEI). The transfection activity was highest on day 3 after administration and remained detectable until day 14. PEG-b-P[Asp(DET)] polyplex nanomicelles were formulated with a therapeutic plasmid bearing the human adrenomedullin (AM) gene and intratracheally administered to rats with monocrotaline-induced pulmonary hypertension. The right ventricular pressure significantly decreased 3 days after administration as confirmed by a notable increase of pulmonary human AM mRNA levels. Intratracheal administration of PEG-b-P[Asp-(DET)] polyplex nanomicelles showed remarkable therapeutic efficacy with PAH animal models without compromising biocompatibility.

Harada-Shiba, Mariko; Takamisawa, Itaru; Miyata, Kanjiro; Ishii, Takehiko; Nishiyama, Nobuhiro; Itaka, Keiji; Kangawa, Kenji; Yoshihara, Fumiki; Asada, Yujiro; Hatakeyama, Kinta; Nagaya, Noriya; Kataoka, Kazunori

2009-01-01

213

Cerebral microvascular inflammation in DOCA salt-induced hypertension: role of angiotensin II and mitochondrial superoxide.  

PubMed

Angiotensin II-mediated hypertension (HTN) is accompanied by a pro-inflammatory and pro-thrombotic state in the cerebral microvasculature. Whether comparable phenotypic changes are elicited in other models of HTN remains unclear. Using wild-type mice with deoxycorticosterone acetate (DOCA) salt-induced HTN and intravital microscopy, we observed significant increases in the adhesion of both leukocytes and platelets in cerebral venules, compared with uninephrectomized control mice, without an accompanying increase in blood-brain barrier permeability. The cell-cell interactions in hypertensive mice were more pronounced after ischemic stroke, but no difference in infarct size was detected. The blood cell recruitment was largely prevented in the following groups of DOCA salt mice: losartan (angiotensin II AT1 receptor blocker) treated, AT1 receptor knockout mice, tempol (a membrane-permeable oxygen radical scavenger) treated, and mito-TEMPO (a mitochondria-targeted antioxidant) treated. A similar pattern of protection was noted in mice subjected to ischemic stroke. The blunted cell recruitment responses were not accompanied by reductions in blood pressure (BP). These findings implicate mitochondria-derived oxygen radicals and angiotensin II in the cerebral inflammation associated with DOCA salt HTN and suggests that BP per se is not a critical determinant of the phenotypic changes that accompany HTN, even after ischemic stroke. PMID:21971354

Rodrigues, Stephen F; Granger, Daniel Neil

2011-10-05

214

Mechanisms underlying the cerebral microvascular responses to angiotensin II-induced hypertension  

PubMed Central

Angiotensin II (AngII) and AngII type-1 receptors (AT1r) have been implicated in the pathogenesis of hypertension and ischemic stroke. The objectives of this study was to determine if/how chronic AngII administration affects blood-brain barrier (BBB) function and blood cell adhesion in the cerebral microvasculature. AngII-loaded osmotic pumps were implanted in wild type (WT) and mutant mice. Leukocyte and platelet adhesion were monitored in cerebral venules by intravital microscopy and BBB permeability detected by Evans blue leakage. AngII(2 wk) infusion increased blood pressure in WT mice. This was accompanied by an increased BBB permeability and a high density of adherent leukocytes and platelets. AT1r (on the vessel wall, but not on blood cells) was largely responsible for the microvascular responses to AngII. Immunodeficient(Rag-1?/?) mice exhibited blunted blood cell recruitment responses without a change in BBB permeability. A similar protection pattern was noted in RANTES?/? and P-selectin?/? mice, with bone marrow chimeras (blood cell deficiency only) yielding responses comparable to the respective knockouts. These findings implicate AT1r in the microvascular dysfunction associated with AngII-induced hypertension and suggest that immune cells and blood cell-associated RANTES and P-selectin contribute to the blood cell recruitment, but not the BBB failure, elicited by AngII.

Vital, Shantel A.; Terao, Satoshi; Nagai, Mutsumi; Granger, D. Neil

2010-01-01

215

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

PubMed Central

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.

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

2009-01-01

216

CYP450 4A inhibition attenuates O2 induced arteriolar constriction in chronic but not acute Goldblatt hypertension.  

PubMed

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 O(2) concentration in the superfusion solution from 0% O(2) to 21% O(2) were determined in the in situ cremaster muscle before and after inhibition of cytochrome P450 4A omega-hydroxylase (CYP450 4A) with N-methyl-sulfonyl-12, 12-dibromododec-11-enamide (DDMS). Arteriolar constriction to elevated PO(2) was enhanced in the chronic 1K1C but not the acute 1K1C or 2K1C. DDMS eliminated O(2)-induced arteriolar constriction in the 9-week 1K1C, but had no effect in the 2-week 1K1C, and only partially inhibited O(2)-induced constriction of arterioles in the 4-week 2K1C rat. These findings indicate that although the CYP4A/20-HETE system contributes to arteriolar constriction in response to elevated PO(2) in the established stage of 1K1C renovascular hypertension, physiological alterations in other mechanisms are the primary determinants of O(2)-induced constriction of arterioles in the early and developing stages of 1K1C and 2K1C hypertension. PMID:19761780

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

2009-09-15

217

Central and Peripheral Mechanisms of T lymphocyte Activation and Vascular Inflammation Produced by Angiotensin II-Induced Hypertension  

PubMed Central

Rationale We have previously found that T lymphocytes are essential for development of angiotensin II-induced hypertension however the mechanisms responsible for T cell activation in hypertension remain undefined. Objective To study the roles of the central nervous system and pressure elevation in T cell activation and vascular inflammation caused by angiotensin II. Methods and Results To prevent the central actions of angiotensin II we created anteroventral third cerebral ventricle (AV3V) lesions in mice. The elevation in blood pressure in response to angiotensin II was virtually eliminated by AV3V lesions, as was activation of circulating T cells and the vascular infiltration of leukocytes. In contrast, AV3V lesioning did not prevent the hypertension and T cell activation caused by the peripheral acting agonist norepinephrine. To determine if T cell activation and vascular inflammation are due to central influences or are mediated by blood pressure elevation, we administered hydralazine (250 mg/L) in the drinking water. Hydralazine prevented the hypertension, and abrogated the increase in circulating activated T cells and vascular infiltration of leukocytes caused by angiotensin II. Conclusions We conclude that the central and pressor effects of angiotensin II are critical for T cell activation and development of vascular inflammation. These findings also support a feed forward mechanism in which modest degrees of blood pressure elevation lead to T cell activation, which in turn promotes inflammation and further raises blood pressure, leading to severe hypertension. Brief summary We have previously shown that T cells are important for the development of hypertension and others have shown that CNS lesions such as AV3V disruption prevent hypertension. We examined the relationship between central actions of angiotensin II, T cell activation and hypertension by determining how AV3V lesions affect T cell activation and hypertensive responses to angiotensin II and norepinephrine. Our data are compatible with a scenario in which modest degrees of pressure elevation, mediated either directly by norepinephrine or via central actions of angiotensin II, promote an inflammatory response that leads to severe hypertension. These studies provide new insight into how the central nervous system contributes to systemic inflammation in hypertension.

Marvar, Paul J.; Thabet, Salim R.; Guzik, Tomasz J.; Lob, Heinrich E.; McCann, Louise A.; Weyand, Connie; Gordon, Frank J.; Harrison, David G.

2010-01-01

218

Comparison of the protective effects of desferrioxamine and ICRF-187 against doxorubicin-induced toxicity in spontaneously hypertensive rats  

Microsoft Academic Search

Since the iron-mediated formation of free radicals is considered to be a critical factor in the pathogenesis of the toxicity of doxorubicin (DXR), comparisons were made of the protective effects of two iron chelators, ICRF-187 and desferrioxamine (DFO), against the chronic cardiac and renal toxicity induced by DXR in spontaneously hypertensive rats (SHR). Two preparations of DFO were studied: DFO

E. H. Herman; Jun Zhang; Victor J. Ferrans

1994-01-01

219

The essential fatty acid status of mother and child in pregnancy-induced hypertension: A prospective longitudinal study  

Microsoft Academic Search

OBJECTIVE: Our purpose was to investigate, in a prospective way, whether the altered essential fatty acid status observed in pregnancy-induced hypertension is a consequence of the disease or may contribute to its cause.STUDY DESIGN: Pregnant women healthy at the start of the study were asked to give a blood sample before 16 weeks, at 22 weeks, and at 32 weeks

Monique D. Al; Adriana C. v. Houwelingen; Anita Badart-Smook; Tom H. Hasaart; Frans J. Roumen; Gerard Hornstra

1995-01-01

220

Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats  

Microsoft Academic Search

Experimental pulmonary hypertension induced in a hypobaric hypoxic environment (HHE) is characterized by structural remodeling of the heart and pulmonary arteries. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) both have diuretic, natriuretic, and hypotensive effects, and both are involved in cardiovascular homeostasis as cardiac hormones. To study the effects of HHE on the natriuretic peptide synthesis system, 170

Kuniaki Nakanishi; Fumiko Tajima; Hiroshi Itoh; Yasuko Nakata; Hiroshi Osada; Norio Hama; Osamu Nakagawa; Kazuwa Nakao; Toshiaki Kawai; Kunio Takishima; Takashi Aurues; Tomosumi Ikeda

2001-01-01

221

Bezafibrate, an anti-hypertriglyceridemic drug, attenuates vascular hyperresponsiveness and elevated blood pressure in fructose-induced hypertensive rats.  

PubMed

A high fructose diet induces hypertension, hyperinsulinemia - insulin resistance, and hypertriglyceridemia (syndrome X). In this study, we investigated the role of an abnormal lipid profile in mediating fructose-induced hypertension. We hypothesized that bezafibrate, a lipid-lowering drug, would reduce elevated blood pressure and inhibit increased vascular reactivity in fructose-fed rats. Male rats were placed on four different diets: group 1 was fed standard chow (n = 6); group 2 was fed 60% fructose (n = 5); group 3 was fed fructose plus bezafibrate (30 mg x kg(-1) x day(-1); drinking water; n = 5); and group 4 was fed standard chow plus bezafibrate (n = 6). In addition, the direct effects of very low density lipoprotein (VLDL) on vascular reactivity were examined. Bezafibrate treatment lowered blood pressure, free fatty acids, and triglycerides in the fructose-fed group, suggesting that lipid abnormalities play a role in the elevation of blood pressure in the fructose-induced hypertensive rat. Aortae from fructose-fed rats were hyperresponsive to the calcium channel agonist Bay K 8644, which was normalized with bezafibrate treatment. Incubation of aortae in a VLDL medium resulted in increased responsiveness to Bay K 8644, lending further support to lipid abnormalities altering vascular reactivity. An altered lipid profile evidenced by elevated triglycerides and free fatty acids is causally related to the development of high blood pressure and increased vascular reactivity in the fructose-induced hypertensive rat. PMID:10588479

Si, X; Webb, R C; Richey, J M

1999-10-01

222

HYPERTENSION INDUCES BRAIN ?-AMYLOID ACCUMULATION, COGNITIVE IMPAIRMENT AND MEMORY DETERIORATION THROUGH ACTIVATION OF RAGE IN BRAIN VASCULATURE  

PubMed Central

Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer’s Disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by Transverse Aortic Constriction, leading to alterations typical of Alzheimer’s Disease, such as amyloid plaques, neuroinflammation, Blood Brain Barrier dysfunction and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer’s Disease of hypertensive mice. We focused on RAGE, that critically regulates A? transport at the Blood Brain Barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE up-regulation in brain vessels of cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal A? deposition. The increased RAGE expression in TAC mice was induced by increased circulating AGEs and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an AGEs inhibitor or antioxidant prevented the development of Alzheimer’s traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal A? deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer’s Disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer.

Carnevale, Daniela; Mascio, Giada; D'Andrea, Ivana; Fardella, Valentina; Bell, Robert D.; Branchi, Igor; Pallante, Fabio; Zlokovic, Berislav; Yan, Shirley ShiDu; Lembo, Giuseppe

2012-01-01

223

Role of Brain Corticosterone and Aldosterone in Central Angiotensin II-Induced Hypertension.  

PubMed

Circulating angiotensin II (Ang II) activates a central aldosterone-mineralocorticoid receptor neuromodulatory pathway, which mediates most of the Ang II-induced hypertension. This study examined whether specific central infusion of Ang II also activates this central aldosterone-mineralocorticoid receptor pathway. Intracerebroventricular infusion of Ang II at 1.0, 2.5, and 12.5 ng/min for 2 weeks caused dose-related increases in water intake, Ang II concentration in the cerebrospinal fluid, and blood pressure. Intracerebroventricular Ang II, at 2.5 and 12.5 ng/min, increased hypothalamic aldosterone and corticosterone, as well as plasma aldosterone and corticosterone without affecting plasma Ang II levels. Intracerebroventricular infusion of the aldosterone synthase inhibitor FAD286-but not the mineralocorticoid receptor blocker eplerenone-inhibited by ?60% the Ang II-induced increase in hypothalamic aldosterone. Both blockers attenuated by ?50% the increase in plasma aldosterone and corticosterone with only minimal effects on hypothalamic corticosterone. By telemetry, intracerebroventricular infusion of Ang II maximally increased blood pressure within the first day with no further increase over the next 2 weeks. Intracerebroventricular infusion of FAD286 or eplerenone did not affect the initial pressor responses but similarly prevented 60% to 70% of the chronic pressor responses to intracerebroventricular infusion of Ang II. These results indicate distinctly different patterns of blood pressure increase by circulating versus central Ang II and support the involvement of a brain aldosterone-mineralocorticoid receptor-activated neuromodulatory pathway in the chronic hypertension caused by both circulating and central Ang II. PMID:23856493

Huang, Bing S; White, Roselyn A; Ahmad, Monir; Leenen, Frans H H

2013-07-15

224

The Beneficial Effect of Suramin on Monocrotaline-Induced Pulmonary Hypertension in Rats  

PubMed Central

Background Pulmonary hypertension (PH) is a progressive disorder characterized by an increase in pulmonary artery pressure and structural changes in the pulmonary vasculature. Several observations indicate that growth factors play a key role in PH by modulating pulmonary artery smooth muscle cell (PA-SMC) function. In rats, established monocrotaline-induced PH (MCT-PH) can be reversed by blocking platelet-derived growth factor receptors (PDGF-R), epidermal growth factor receptors (EGF-R), or fibroblast growth factor receptors (FGF-R). All these receptors belong to the receptor tyrosine kinase (RTK) family. Methods and Results We evaluated whether RTK blockade by the nonspecific growth factor inhibitor, suramin, reversed advanced MCT-PH in rats via its effects on growth-factor signaling pathways. We found that suramin inhibited RTK and ERK1/2 phosphorylation in cultured human PA-SMCs. Suramin inhibited PA-SMC proliferation induced by serum, PDGF, FGF2, or EGF in vitro and ex vivo. Treatment with suramin from day 1 to day 21 after monocrotaline injection attenuated PH development, as shown by lower values for pulmonary artery pressure, right ventricular hypertrophy, and distal vessel muscularization on day 21 compared to control rats. Treatment with suramin from day 21 to day 42 after monocrotaline injection reversed established PH, thereby normalizing the pulmonary artery pressure values and vessel structure. Suramin treatment suppressed PA-SMC proliferation and attenuated both the inflammatory response and the deposition of collagen. Conclusions RTK blockade by suramin can prevent MCT-PH and reverse established MCT-PH in rats. This study suggests that an anti-RTK strategy that targets multiple RTKs could be useful in the treatment of pulmonary hypertension.

Izikki, Mohamed; Mercier, Olaf; Lecerf, Florence; Lubert Guin, Lauriane; Hoang, Eric; Dorfmuller, Peter; Perros, Frederic; Humbert, Marc; Simonneau, Gerald; Dartevelle, Philippe; Fadel, Elie; Eddahibi, Saadia

2013-01-01

225

Effect of A-HRS on blood pressure and metabolic alterations in fructose-induced hypertensive rats  

Microsoft Academic Search

Fructose feeding induces a rise in blood pressure in normal rats that is associated with insulin resistance, hyperinsulinemia, hyperglycaemia, hypercholesterolaemia and hypertriglyceridaemia. We have examined the effect of chronic administration of A-HRS (100 and 300?mg?kg; p.o.) isolated from Hibiscus rosa sinensis (Malvaceae) on systolic blood pressure (SBP), vascular reactivity, serum glucose, triglycerides, cholesterol, uric acid and insulin in fructose-induced hypertension

Mahalaxmi Mohan; Bhagyashree Khade; Amol Shinde

2011-01-01

226

Effect of A-HRS on blood pressure and metabolic alterations in fructose-induced hypertensive rats  

Microsoft Academic Search

Fructose feeding induces a rise in blood pressure in normal rats that is associated with insulin resistance, hyperinsulinemia, hyperglycaemia, hypercholesterolaemia and hypertriglyceridaemia. We have examined the effect of chronic administration of A-HRS (100 and 300?mg?kg; p.o.) isolated from Hibiscus rosa sinensis (Malvaceae) on systolic blood pressure (SBP), vascular reactivity, serum glucose, triglycerides, cholesterol, uric acid and insulin in fructose-induced hypertension

Mahalaxmi Mohan; Bhagyashree Khade; Amol Shinde

2012-01-01

227

Alterations in phenylephrine-induced contractions and the vascular expression of Na+,K+-ATPase in ouabain-induced hypertension  

PubMed Central

Hypertension development, phenylephrine-induced contraction and Na+,K+-ATPase functional activity and protein expression in aorta (AO), tail (TA) and superior mesenteric (SMA) arteries from ouabain- (25??g day?1, s.c., 5 weeks) and vehicle-treated rats were evaluated.Ouabain treatment increased systolic blood pressure (127±1 vs 160±2?mmHg, n=24, 35; P<0.001) while the maximum response to phenylephrine was reduced (P<0.01) in AO (102.8±3.9 vs 67.1±10.1% of KCl response, n=12, 9) and SMA (82.5±7.5 vs 52.2±5.8%, n=12, 9).Endothelium removal potentiated the phenylephrine response to a greater extent in segments from ouabain-treated rats. Thus, differences of area under the concentration-response curves (dAUC) in endothelium-denuded and intact segments for control and ouabain-treated rats were, respectively: AO, 56.6±9.6 vs 198.3±18.3 (n=9, 7); SMA, 85.5±15.4 vs 165.4±24.8 (n=6, 6); TA, 13.0±6.1 vs 39.5±10.4% of the corresponding control AUC (n=6, 6); P<0.05.The relaxation to KCl (1?–?10?mM) was similar in segments from both groups. Compared to controls, the inhibition of 0.1?mM ouabain on KCl relaxation was greater in AO (dAUC: 64.8±4.6 vs 84.0±5.1%, n=11, 14; P<0.05), similar in SMA (dAUC: 39.1±3.9 vs 43.3±7.8%, n=6, 7; P>0.05) and smaller in TA (dAUC: 62.1±5.5 vs 41.4±8.2%, n=12, 13; P<0.05) in ouabain-treated rats.Protein expression of both ?1 and ?2 isoforms of Na+,K+-ATPase was augmented in AO, unmodified in SMA and reduced in TA from ouabain-treated rats.These results suggest that chronic administration of ouabain induces hypertension and regional vascular alterations, the latter possibly as a consequence of the hypertension.

Rossoni, Luciana V; Salaices, Mercedes; Marin, Jesus; Vassallo, Dalton V; Alonso, Maria J

2002-01-01

228

Transient left ventricular apical ballooning and exercise induced hypertension during treadmill exercise testing: is there a common hypersympathetic mechanism?  

PubMed Central

Objective To describe two cases of Takotsubo like myocardial contractile pattern during exercise stress test secondary to hypertensive response. Background Treadmill exercise testing is known to cause sympathetic stimulation, leading to increased levels of catecholamine, resulting in alteration in vascular tone. Hypertensive response during exercise testing can cause abnormal consequences, resulting in false positive results. Cases We present the cases of two patients experiencing apical and basal akinesis during exercise stress echocardiography, in whom normal wall motion response was observed on subsequent pharmacologic stress testing. The first patient developed transient left ventricular (LV) apical akinesis during exercise stress echocardiography. Due to high suspicion that this abnormality might be secondary to hypertensive response, pharmacologic stress testing was performed after three days, which was completely normal and showed no such wall motion abnormality. Qualitative assessment of myocardial perfusion using contrast was also performed, which showed good myocardial blood flow, indicating low probability for significant obstructive coronary artery disease. The second patient developed LV basal akinesis as a result of hypertensive response during exercise testing. Coronary angiogram was not performed in either patient due to low suspicion for coronary artery disease, and subsequently negative stress studies. Results Transient stress induced cardiomyopathy can develop secondary to hypertensive response during exercise stress testing. Conclusion These cases provide supporting evidence to the hyper-sympathetic theory of left ventricular ballooning syndrome.

Dhoble, Abhijeet; Abdelmoneim, Sahar S; Bernier, Mathieu; Oh, Jae K; Mulvagh, Sharon L

2008-01-01

229

Helium-induced cardioprotection of healthy and hypertensive rat myocardium in vivo.  

PubMed

Helium protects healthy myocardium against ischemia/reperfusion injury by early and late preconditioning (EPC, LPC) and postconditioning (PostC). We investigated helium-induced PostC of the hypertensive heart and enhancement by addition of LPC and EPC. We also investigated involvement of signaling kinases glycogen synthase kinase 3 beta (GSK-3?) and protein kinase C-epsilon (PKC-?). To assess myocardial cell damage, we performed infarct size measurements in healthy Wistar Kyoto (WKY rats, n=8-9) and Spontaneous Hypertensive rats (SHR, n=8-9) subjected to 25 min ischemia and 120 min reperfusion. Rats inhaled 70% helium for 15 min after index ischemia (PostC), combined with 15 min helium 24h prior to index ischemia (LPC+PostC), a triple intervention with additional 3 short cycles of 5 min helium inhalation shortly before ischemia (EPC+LPC+PostC), or no further treatment. In WKY rats, PostC reduced infarct size from 46 ± 2% (mean ± S.E.M) in the control group to 29 ± 2%. LPC+PostC or EPC+LPC+PostC reduced infarct sizes to a similar extent (30 ± 3% and 32 ± 2% respectively). In SHR, EPC+LPC+PostC reduced infarct size from 53 ± 3% in control to 39 ± 3%, while PostC or LPC+PostC alone were not protective; infarct size 48 ± 4% and 44 ± 4%, respectively. Neither PostC in WKY rats nor EPC+LPC+PostC in SHR was associated with an increase in phosphorylation of GSK-3? and PKC-? after 15 min of reperfusion. Concluding, a triple intervention of helium conditioning results in cardioprotection in SHR, whereas a single intervention does not. In WKY rats, the triple intervention does not further augment protection. Helium conditioning is not associated with a mechanism involving GSK-3? and PKC-?. PMID:22497999

Oei, Gezina T M L; Huhn, Ragnar; Heinen, Andre; Hollmann, Markus W; Schlack, Wolfgang S; Preckel, Benedikt; Weber, Nina C

2012-04-03

230

Brain Na+,K+-ATPase isozyme activity and protein expression in ouabain-induced hypertension.  

PubMed

In normotensive rats, chronic infusion of exogenous ouabain causes hypertension involving central mechanisms. To determine whether ouabain-induced hypertension is associated with specific changes in brain Na+,K+-ATPase activity and expression, we assessed brain Na+,K+-ATPase isozyme activity and protein expression in rats treated with ouabain (50 microg/day s.c. or 10 microg/day i.c.v. for 14 days). Resting mean arterial pressure (MAP) was higher in s.c.- and i.c.v.-ouabain-treated animals vs. control (124+/-2 vs. 105+/-2 and 130+/-2 vs. 109+/-2, respectively, p<0.01). Ouabain infused s.c. or i.c.v. for 14 days had no effect on Na+,K+-ATPase isozyme activity in hypothalamic, pontine/medullary or cortical microsomes. However, the percent increase in total Na+,K+-ATPase activity produced in vitro by antibody Fab fragments that bind ouabain with high affinity (Digibind) was two-fold greater in s.c.- and i.c.v.-ouabain-treated rats vs. control, but only in hypothalamic microsomes. Thus, ouabain infused s.c. or i.c.v. does appear to directly inhibit Na+,K+-ATPase activity in the hypothalamus. On the other hand, in the hypothalamus, s.c.- and i.c.v.-ouabain infusions tended to increase alpha3 (by 30-44%), but had no effect on alpha1 or alpha2 Na+,K+-ATPase isozyme protein expression. In addition, ouabain was found to partially dissociate from the Na+,K+-ATPase enzyme following sample processing. Thus, the inability to detect a decrease in enzyme activity in the hypothalamus in response to ouabain may be due, in part, to an increase in enzyme expression and the dissociation of ouabain during sample processing. PMID:15276875

Kent, Mary-Anne H; Huang, Bing S; Van Huysse, James W; Leenen, Frans H H

2004-08-27

231

Contribution of renal purinergic receptors to renal vasoconstriction in angiotensin II-induced hypertensive rats.  

PubMed

To investigate the participation of purinergic P2 receptors in the regulation of renal function in ANG II-dependent hypertension, renal and glomerular hemodynamics were evaluated in chronic ANG II-infused (14 days) and Sham rats during acute blockade of P2 receptors with PPADS. In addition, P2X1 and P2Y1 protein and mRNA expression were compared in ANG II-infused and Sham rats. Chronic ANG II-infused rats exhibited increased afferent and efferent arteriolar resistances and reductions in glomerular blood flow, glomerular filtration rate (GFR), single-nephron GFR (SNGFR), and glomerular ultrafiltration coefficient. PPADS restored afferent and efferent resistances as well as glomerular blood flow and SNGFR, but did not ameliorate the elevated arterial blood pressure. In Sham rats, PPADS increased afferent and efferent arteriolar resistances and reduced GFR and SNGFR. Since purinergic blockade may influence nitric oxide (NO) release, we evaluated the role of NO in the response to PPADS. Acute blockade with N(?)-nitro-l-arginine methyl ester (l-NAME) reversed the vasodilatory effects of PPADS and reduced urinary nitrate excretion (NO(2)(-)/NO(3)(-)) in ANG II-infused rats, indicating a NO-mediated vasodilation during PPADS treatment. In Sham rats, PPADS induced renal vasoconstriction which was not modified by l-NAME, suggesting blockade of a P2X receptor subtype linked to the NO pathway; the response was similar to that obtained with l-NAME alone. P2X1 receptor expression in the renal cortex was increased by chronic ANG II infusion, but there were no changes in P2Y1 receptor abundance. These findings indicate that there is an enhanced P2 receptor-mediated vasoconstriction of afferent and efferent arterioles in chronic ANG II-infused rats, which contributes to the increased renal vascular resistance observed in ANG II-dependent hypertension. PMID:21367914

Franco, Martha; Bautista, Rocio; Tapia, Edilia; Soto, Virgilia; Santamaría, José; Osorio, Horacio; Pacheco, Ursino; Sánchez-Lozada, L Gabriela; Kobori, Hiroyuki; Navar, L Gabriel

2011-03-02

232

Microtubule proliferation in right ventricular myocytes of rats with monocrotaline-induced pulmonary hypertension  

PubMed Central

Microtubules are components of the cardiac cytoskeleton that can proliferate in response to pressure-overload in animal and human heart failure. We wished to test whether there was a proliferation of the microtubule cytoskeleton in the right ventricle of rats with pulmonary hypertension induced by monocrotaline (MCT) and whether this contributed to contractile dysfunction. Male Wistar rats were injected with 60 mg/kg of MCT in saline or an equivalent volume of saline (CON). MCT produced clinical signs of heart failure within 4 weeks of injection. Expression of right ventricular mRNA for ?-tubulin was measured by real-time reverse transcription polymerase chain reaction. Free and polymerised fractions of ?-tubulin protein were assessed using Western blot analysis and immunofluorescence microscopy was used to assess tyrosinated and acetylated (stabilized) microtubules. Right ventricular myocyte contraction was measured in response to the microtubule de-polymeriser colchicine (10 ?mol/l for at least 1 h). Compared to CON, in MCT right ventricles there was a small but statistically significant increase in the expression of mRNA for ?-tubulin (P < 0.001); total (P < 0.05) and polymerised fraction (P < 0.01) of ?-tubulin protein and level of acetylated tubulin (P < 0.01). However colchicine treatment did not increase the contraction of MCT myocytes (P > 0.05) or affect their response to increased stimulation frequency. Our observations support the hypothesis that microtubule proliferation is a common response to pulmonary hypertension in failing right ventricles but suggest that the effect this has on contraction depends upon the specific experimental or clinical conditions that prevail and the subsequent level of microtubule proliferation.

Stones, Rachel; Benoist, David; Peckham, Michelle; White, Ed

2013-01-01

233

Antihypertensive effect of riboflavin analogs in rats with mineralocorticoid-induced hypertension.  

PubMed

This study investigated whether the riboflavin analogs, 7,8-dimethyl-10-formylmethyl isoalloxazine (FMI) and 7,8-dimethyl-10-(2'-hydroxyethyl) isoalloxazine (HEI), are effective antihypertensive agents in mineralocorticoid-induced or deoxycorticosterone acetate (DOCA)-salt hypertension. These studies are based on our previous observation tht aldosterone enhances the biosynthesis of renal flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) from riboflavin, and that FMI and HEI competitively inhibit conversion of riboflavin to FMN and reabsorption of Na+ in the kidney of adrenalectomized rats. When 1.6 mg of FMI or HEI were administered simultaneously with 3.0 mg of DOCA, the tail systolic blood pressure (SBP) of unanesthetized rats rose only to 136 +/- 5 mm Hg (standard error of the mean, SEM) compared to 163 +/- 5 mm Hg during DOCA therapy alone (p less than 0.0005). This hypotensive effect of FMI or HEI was noted after the fourth week of treatment and persisted through the ninth week. The rats tolerated the medication well and had no signs of riboflavin deficiency. DOCA administration alone resulted in a 24% increase in iliopsoas muscle Na+ concentration (p less than 0.0005), and a 0.8% increase in the water content of the muscle (p less than 0.025), suggesting a positive Na+ balance. Administration of FMI or HEI blunted the ability of DOCA to increase muscle Na+ concentration (p less than 0.025), water content (p less than 0.01). HEI treatment of the Kyoto strain of spontaneously hypertensive rats (SHR) did not lower their mean SBP. Thus it appears that the hypotensive actions of FMI or HEI are closely associated with their ability to modify the effects of mineralocorticoids on NA+ balance. PMID:7203608

Trachewsky, D

234

Pulmonary hypertension and edema induced by platelet-activating factor in isolated, perfused rat lungs are blocked by BN52021.  

PubMed

The experimental intravenous administration of platelet activating factor (PAF) induces pulmonary hypertension and directly or indirectly increases capillary permeability. Selective PAF antagonists BN52021 and L652-731 have been shown to inhibit the action of PAF in vitro and in vivo. Using a unique isolated perfused rat lung model, we measured the effect of these PAF antagonists on PAF-induced pulmonary hypertension and edema. Isolated rat lungs were perfused with Krebs-Henseleit solution. The right and left pulmonary arteries were dissected so that they could be perfused selectively, permitting the use of one lung as an internal control for a specific pharmacologic challenge. Exposure of one lung to PAF induced an increase of perfusion pressure and wet/dry lung weight ratio in a dose-dependent manner compared with the control lung. The PAF antagonists attenuated the increase in perfusion pressure and wet/dry lung weight caused by PAF (0.75 micrograms) in a dose-dependent manner. In addition, prostaglandin F2 alpha induced an equivalent increase in pulmonary pressure without causing a similar increase in lung edema. PAF-induced pulmonary hypertension and the increase in wet/dry lung weight ratio appear to be PAF receptor-mediated processes, and the use of specific antagonists and this technique may be useful probes to determine the role of PAF in pathophysiologic states. PMID:3339274

Imai, T; Vercellotti, G M; Moldow, C F; Jacob, H S; Weir, E K

1988-02-01

235

Increased NPY activity in the PVN contributes to food-restriction induced reductions in blood pressure in aortic coarctation hypertensive rats  

Microsoft Academic Search

We hypothesized that hypothalamic NPYergic mechanisms mediate the blood pressure lowering effect of caloric restriction in hypertensive rats. Aortic coarctation-induced (AC) hypertensive rats (n=25) were assigned to either an ad libitum fed control group (AL) or food restricted group (FR; 60% of AL consumption) for 3 weeks. Rats were instrumented chronically with vascular catheters and bilateral guide cannulae directed at

J. Mark VanNess; Jamie E DeMaria; J. Michael Overton

1999-01-01

236

Proteomic Analysis of the Trabecular Meshwork of Rats in a Steroid-Induced Ocular Hypertension Model: Downregulation of Type I Collagen C-Propeptides  

Microsoft Academic Search

Purpose: To investigate global protein expression profiles in the trabecular meshwork (TM) of normal and glucocorticoid-induced ocular hypertensive rat eyes by proteomic analysis, which has not yet been conducted to date. Materials and Methods: A rat ocular hypertension model was produced by topical application of dexamethasone (DEX) for 4 weeks. Age-matched untreated rats served as controls. Intraocular pressure (IOP) was

Manabu Shinzato; Yoshito Yamashiro; Nariko Miyara; Akihiro Iwamatsu; Kouji Takeuchi; Masato Umikawa; Maitsetseg Bayarjargal; Ken-ichi Kariya; Shoichi Sawaguchi

2007-01-01

237

Emblica officinalis Exerts Antihypertensive Effect in a Rat Model of DOCA-Salt-Induced Hypertension: Role of (p) eNOS, NO and Oxidative Stress  

Microsoft Academic Search

Emblica officinalis (EO) has antioxidant properties that could improve redox-sensitive vascular, cardiac and renal changes associated with deoxycorticosterone\\u000a acetate\\/1% NaCl high salt (DOCA\\/HS)-induced hypertension. We determined whether hydroalcoholic lyophilized extract of EO may\\u000a influence DOCA\\/HS-induced hypertension by modulating activity of (p) eNOS and endogenous antioxidants. Hypertension was induced\\u000a in rats by DOCA-salt (20 mg\\/kg, s.c.) twice weekly for 5 weeks and replacing

Jagriti BhatiaFauzia; Fauzia Tabassum; Ashok Kumar Sharma; Saurabh Bharti; Mahaveer Golechha; Sujata Joshi; Abhay Krishna Srivastava; Dharamvir Singh Arya

2011-01-01

238

Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat.  

PubMed

1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats. PMID:17042910

Mondo, Charles K; Yang, Wan-Song; Zhang, Nan; Huang, Ti-Gang

2006-11-01

239

Impaired vasomotor function induced by the combination of hypertension and hypercholesterolemia.  

PubMed

Although it is well known that endothelial function is compromised in the presence of either hypertension (HTN) or hypercholesterolemia (HCh), less is known about whether and how the combination of these risk factors (HTN+HCh) results in impaired endothelium-dependent dilation (EDD). The aims of this study were to evaluate the influence of HTN+HCh on vasomotor function and to identify the mechanisms that underlie the altered vascular reactivity elicited by HTN+HCh. Endothelium-dependent and -independent vasomotor responses of aortic vessels were studied in mice with diet-induced HCh and/or HTN induced by chronic administration of either angiotensin II (AngII) or deoxycorticosterone acetate-salt. HTN+HCh elicited an impairment of EDD that appeared between each risk factor alone. Incubation with catalase resulted in more severe EDD impairment. Each risk factor enhanced vascular H?O? production, but a larger response was noted with HTN+HCh. An attenuated EDD was not observed in AngII type 1a receptor deficient (AT1r(-/-)) mice, but AT1r(-/-) bone marrow chimeras exhibited more profound impairment compared with wild-type. HTN+HCh does not exert an additive effect of vasomotor dysfunction compared with either risk factor alone, and both H?O? and blood cell-associated AT1r contribute to the impaired EDD responses in mice with HTN+HCh. PMID:23321401

Kurtel, Hizir; Rodrigues, Stephen F; Yilmaz, Cigdem E; Yildirim, Alper; Granger, D Neil

240

Pyrrolidine dithiocarbamate attenuates the development of monocrotaline-induced pulmonary arterial hypertension.  

PubMed

We aimed to demonstrate the potential protective effects of pyrrolidine dithiocarbamate (PDTC) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Adult male rats were randomly assigned to 4 groups: control group, MCT-treated rats only, MCT-injected rats treated with PDTC, and PDTC-treated rats only. Blood and tissue samples were collected after the sacrifice. Levels of malondialdehyde (MDA) were measured by using the thiobarbituric acid method. Total antioxidant status (TAS) was determined using a commercially available ImAnOx kit. A histopathological evaluation was accomplished by scoring the degree of severity. Endothelial damage of the main pulmonary artery was evaluated by immunohistochemical labeling of endothelial cells using anti-rat endothelial cell antigen 1 (RECA-1) antibody. MCT-induced right ventricular hypertrophy (RVH) was reduced significantly in the MCT+PDTC-treated group. MDA levels were significantly lowered in the MCT+PDTC-treated group. TAS was significantly higher in the MCT+PDTC-treated group when compared with the rats with PAH. Histopathological examination demonstrated that PDTC treatment reduced the development of inflammation, hemorrhage and congestion, and collagen deposition. In conclusion, PDTC attenuated PAH and protected pulmonary endothelium in rats administered MCT. These findings suggest that PDTC treatment may provide a new effective therapeutic approach in the treatment of PAH. PMID:23582365

Yavuz, Taner; Uzun, Ozge; Macit, Asli; Comunoglu, Cem; Yavuz, Ozlem; Silan, Coskun; Yuksel, Hatice; Yildirim, Hayriye Ak

2013-03-15

241

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

PubMed

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

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

242

An inducible transgenic mouse model for familial hypertension with hyperkalaemia (Gordon's syndrome or pseudohypoaldosteronism type II).  

PubMed

Mutations in the novel serine/threonine WNK [With No lysine (=K)] kinases WNK1 and WNK4 cause PHAII (pseudohypoaldosteronism type II or Gordon's syndrome), a rare monogenic syndrome which causes hypertension and hyperkalaemia on a background of a normal glomerular filtration rate. Current animal models for PHAII recapitulate some aspects of the disease phenotype, but give no clues to how rapidly the phenotype emerges or whether it is reversible. To this end we have created an inducible PHAII transgenic animal model that expresses a human disease-causing WNK4 mutation, WNK4 Q565E, under the control of the Tet-On system. Several PHAII inducible transgenic mouse lines were created, each with differing TG (transgene) copy numbers and displaying varying degrees of TG expression (low, medium and high). Each of these transgenic lines demonstrated similar elevations of BP (blood pressure) and plasma potassium after 4 weeks of TG induction. Withdrawal of doxycycline switched off mutant TG expression and the disappearance of the PHAII phenotype. Western blotting of microdissected kidney nephron segments confirmed that expression of the thiazide-sensitive NCC (Na?-Cl? co-transporter) was increased, as expected, in the distal convoluted tubule when transgenic mice were induced with doxycycline. The kidneys of these mice also do not show the morphological changes seen in the previous transgenic model expressing the same mutant form of WNK4. This inducible model shows, for the first time, that in vivo expression of a mutant WNK4 protein is sufficient to cause the rapid and reversible appearance of a PHAII disease phenotype in mice. PMID:23336180

Chowdhury, Jabed A; Liu, Che-Hsiung; Zuber, Annie M; O'Shaughnessy, Kevin M

2013-06-01

243

Cilnidipine lowered psychological stress-induced increase in blood pressure in a hypertensive man: a case report  

PubMed Central

Background In some hypertensive patients, psychological stress makes blood pressure difficult to control and causes physical symptoms such as headache or dizziness. We report the case of a hypertensive man whose psychological stress-induced increase in blood pressure was attenuated by cilnidipine. Case Presentation The patient (a 72-year-old man) had hypertension and was on antihypertensive therapy. When mentally concentrating, he experienced occipital headaches and dizziness, and despite thorough testing, no abnormality was found. He was subsequently referred to our department. The mirror drawing test (MDT), a psychological stress test, increased blood pressure by about 40 mmHg, and the patient described occipital headache. Plasma noradrenaline level also increased from 212 to 548 pg/ml. We therefore switched the patient from nifedipine, an L-type calcium (Ca) channel blocker, to cilnidipine, an L-type/N-type Ca channel blocker with suppressive effects on sympathetic activity. Cilnipidine attenuated MDT-induced an increase in blood pressure and plasma noradrenaline level and prevented the development of headache during testing. Conclusion These findings suggest that cilnidipine is a useful antihypertensive agent for hypertensive patients in whom psychological stress causes marked fluctuations in blood pressure.

Hayashida, Sota; Oka, Takakazu; Tsuji, Sadatoshi

2007-01-01

244

The iron chelator pyridoxal isonicotinoyl hydrazone (PIH) and its analogues prevent damage to 2-deoxyribose mediated by ferric iron plus ascorbate  

Microsoft Academic Search

Iron chelating agents are essential for treating iron overload in diseases such as ?-thalassemia and are potentially useful for therapy in non-iron overload conditions, including free radical mediated tissue injury. Deferoxamine (DFO), the only drug available for iron chelation therapy, has a number of disadvantages (e.g., lack of intestinal absorption and high cost). The tridentate chelator pyridoxal isonicotinoyl hydrazone (PIH)

Marcelo Hermes-Lima; Prem Ponka; Herbert M. Schulman

2000-01-01

245

Apocynin but Not l-Arginine Prevents and Reverses Dexamethasone-Induced Hypertension in the Rat  

Microsoft Academic Search

Background: Dexamethasone (Dex)–hypertension in rats is associated with increased oxidative stress. We investigated effects of the NAD(P)H oxidase inhibitor apocynin and the nitric oxide (NO) precursor L-arginine on Dex-hypertension to determine the relative roles of NAD(P)H oxidase and uncoupling in the reactive oxygen species (ROS) generation and hypertension.Methods: Male Sprague-Dawley rats (n = 10\\/group) received Dex (20 ?g\\/kg\\/day subcutaneously) or

Lexian Hu; Yi Zhang; Pek S. Lim; Yuchun Miao; Chrismin Tan; Christopher G. Schyvens; Judith A. Whitworth

2006-01-01

246

Gene Expression of Endothelin-1 and Endothelin Receptor A on Monocrotaline-Induced Pulmonary Hypertension in Rats After Bosentan Treatment  

PubMed Central

Background and Objectives Endothelin (ET)-1, a potent endothelium-derived vasoconstrictor peptide, has a potential pathophysiologic role in pulmonary hypertension. Bosentan, a dual ET receptor (ETA/ETB) antagonist, is efficacious in treatment of pulmonary hypertension. The objectives of this study were to investigate the expression of ET-1 and ET receptor A (ERA) genes and to evaluate the effect of bosentan in monocrotaline (MCT)-induced pulmonary hypertension. Materials and Methods Four-week-old male Sprague-Dawley rats were treated as follows: control (n=36), subcutaneous (sc) injection of saline; MCT (n=36), sc injection of MCT (60 mg/kg); and bosentan (n=36), sc injection of MCT (60 mg/kg) plus 25 mg/kg/day bosentan orally. Results Serum ET-1 concentrations in the MCT group were higher than the control group on day 28 and 42. Quantitative analysis of peripheral pulmonary arteries revealed that the increase in medial wall thickness after MCT injection was significantly attenuated in the bosentan group on day 28 and 42. In addition, the increase in the number of intra-acinar muscular arteries after MCT injection was reduced by bosentan on day 14, 28 and 42. The levels of ET-1 and ERA gene expression were significantly increased in the MCT group compared with control group on day 5, and bosentan decreased the expression of ET-1 on day 5. Conclusion ET-1 contributes to the progression of cardiopulmonary pathology in rats with MCT-induced pulmonary hypertension. Administration of bosentan reduced ET-1 gene expression in MCT-induced pulmonary hypertension in rats.

Lim, Kyoung Ah; Kim, Kwan Chang; Cho, Min-Sun; Lee, Bo En; Kim, Hae Soon

2010-01-01

247

Doxycycline ameliorates 2K-1C hypertension-induced vascular dysfunction in rats by attenuating oxidative stress and improving nitric oxide bioavailability.  

PubMed

Vascular dysfunction associated with two-kidney, one-clip (2K-1C) hypertension may result from both altered matrix metalloproteinase (MMP) activity and higher concentrations of reactive oxygen species (ROS). Doxycycline is considering the most potent MMP inhibitor of tetracyclines and attenuates 2K-1C hypertension-induced high blood pressure and chronic vascular remodeling. Doxycycline might also act as a ROS scavenger and this may contribute to the amelioration of some cardiovascular diseases associated with increased concentrations of ROS. We hypothesized that in addition to its MMP inhibitory effect, doxycycline attenuates oxidative stress and improves nitric oxide (NO) bioavailability in 2K-1C hypertension, thus improving hypertension-induced arterial endothelial dysfunction. Sham operated or 2K-1C hypertensive rats were treated with doxycycline 30 mg/kg/day (or vehicle). After 8 weeks of treatment, aortic rings were isolated to assess endothelium dependent vasorelaxation to A23187. Arterial and systemic levels of ROS were respectively measured using dihydroethidine (DHE) and thiobarbituric acid reactive substances (TBARS). Neutrophils-derived ROS were tested in vitro using the fluoroprobe Carboxy-H(2)DCFDA and human neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA). NO levels were assessed in rat aortic endothelial cells by confocal microscopy. Aortic MMP activity was determined by in situ zymography. Doxycycline attenuated 2K-1C hypertension (169 ± 17.3 versus 209 ± 10.9mm Hg in hypertensive controls, p<0.05) and protected against hypertension-induced reduction in endothelium-dependent vasorelaxation to A23187 (p<0.05). Doxycycline also decreased hypertension-induced oxidative stress (p<0.05), higher MMP activity (p<0.01) and improved NO levels in aortic endothelial cells (p<0.01). Therefore, doxycycline ameliorates 2K-1C hypertension-induced endothelial dysfunction in aortas by inhibiting oxidative stress generation and improving NO bioavailability, in addition to its inhibitory effects on MMP activity. PMID:22327038

Castro, Michele M; Rizzi, Elen; Ceron, Carla S; Guimaraes, Danielle A; Rodrigues, Gerson J; Bendhack, Lusiane M; Gerlach, Raquel F; Tanus-Santos, Jose Eduardo

2012-02-03

248

Antihypertensive effect of gomisin A from Schisandra chinensis on angiotensin II-induced hypertension via preservation of nitric oxide bioavailability  

PubMed Central

Gomisin A (GA) is a small molecular weight lignan present in Schisandra chinensis, and has been demonstrated to have vasodilatory activity. In the present study, we investigated the effect of GA on blood pressure (BP) in angiotensin II (Ang II)-induced hypertensive mice. C57/BL6 mice infused subcutaneously with Ang II (1 and 2??g?kg?1 per min for 2 weeks) showed an increase in BP with a decrease in nitric oxide (NO) metabolites in plasma, and a negative correlation between these two parameters was demonstrated. In the thoracic aorta from Ang II-induced hypertensive mice, a decrease in vascular NO that was accompanied by a diminution of phosphorylated endothelial nitric oxide synthase (eNOS), as well as by increased reactive oxygen species (ROS) production, was demonstrated. These alterations in BP, eNOS phosphorylation and ROS production in the vasculature of Ang II-treated mice were markedly and dose-dependently reversed by simultaneous administration of GA (2 and 10??g?kg?1 per min). In addition, Ang II-induced ROS production in cultured vascular cells such as endothelial cells and vascular smooth muscle cells was markedly attenuated by GA. These results suggested that GA attenuated the increase in BP via preservation of vascular NO bioavailability not only by inhibiting ROS production but also by preventing the impairment of eNOS function in the vasculature of Ang II-induced hypertensive mice.

Young Park, Ji; Wook Yun, Jung; Whan Choi, Young; Ung Bae, Jin; Won Seo, Kyo; Jin Lee, Seung; Youn Park, So; Whan Hong, Ki; Kim, Chi Dae

2012-01-01

249

Sustained Ocular Hypertension Induces Dendritic Degeneration of Mouse Retinal Ganglion Cells That Depends on Cell Type and Location  

PubMed Central

Purpose. Glaucoma is characterized by retinal ganglion cell (RGC) death and frequently associated with elevated IOP. How RGCs degenerate before death is little understood, so we sought to investigate RGC degeneration in a mouse model of ocular hypertension. Methods. A laser-induced mouse model of chronic ocular hypertension mimicked human high-tension glaucoma. Immunohistochemistry was used to characterize overall RGC loss and an optomotor behavioral test to measure corresponding changes in visual capacity. Changes in RGC functional properties were characterized by a large-scale multielectrode array (MEA). The transgenic Thy-1-YFP mouse line, in which a small number of RGCs are labeled with yellow fluorescent protein (YFP), permitted investigation of whether subtypes of RGCs or RGCs from particular retinal areas were differentially vulnerable to elevated IOP. Results. Sustained IOP elevation in mice was achieved by laser photocoagulation. We confirmed RGC loss and decreased visual acuity in ocular hypertensive mice. Furthermore, these mice had fewer visually responsive cells with smaller receptive field sizes compared to controls. We demonstrated that RGC dendritic shrinkage started from the vertical axis of hypertensive eyes and that mono-laminated ON cells were more susceptible to IOP elevation than bi-laminated ON-OFF cells. Moreover, a subgroup of ON RGCs labeled by the SMI-32 antibody exhibited significant dendritic atrophy in the superior quadrant of the hypertensive eyes. Conclusions. RGC degeneration depends on subtype and location in hypertensive eyes. This study introduces a valuable model to investigate how the structural and functional degeneration of RGCs leads to visual impairments.

Feng, Liang; Zhao, Yan; Yoshida, Miho; Chen, Hui; Yang, Jessica F.; Kim, Ted S.; Cang, Jianhua; Troy, John B.; Liu, Xiaorong

2013-01-01

250

Hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELM?) induces the vascular and hemodynamic changes of pulmonary hypertension  

PubMed Central

Pulmonary hypertension (PH) is a serious disease of multiple etiologies mediated by hypoxia, immune stimuli, and elevated pulmonary pressure that leads to vascular thickening and eventual right heart failure. In a chronic hypoxia model of PH, we previously reported the induction of a novel pleiotropic cytokine, hypoxia-induced mitogenic factor (HIMF), that exhibits mitogenic, vasculogenic, contractile, and chemokine properties during PH-associated vascular remodeling. To examine the role of HIMF in hypoxia-induced vascular remodeling, we performed in vivo knockdown of HIMF using short hairpin RNA directed at rat HIMF in the chronic hypoxia model of PH. Knockdown of HIMF partially blocked increases in mean pulmonary artery pressure, pulmonary vascular resistance, right heart hypertrophy, and vascular remodeling caused by chronic hypoxia. To demonstrate a direct role for HIMF in the mechanism of PH development, we performed HIMF-gene transfer into the lungs of rats using a HIMF-expressing adeno-associated virus (AAV). AAV-HIMF alone caused development of PH similar to that of chronic hypoxia with increased mean pulmonary artery pressure and pulmonary vascular resistance, right heart hypertrophy, and neomuscularization and thickening of small pulmonary arterioles. The findings suggest that HIMF represents a critical cytokine-like growth factor in the development of PH.

Angelini, Daniel J.; Su, Qingning; Yamaji-Kegan, Kazuyo; Fan, Chunling; Skinner, John T.; Champion, Hunter C.; Crow, Michael T.; Johns, Roger A.

2009-01-01

251

Immunoglobulin G anti-endothelial cell antibodies: inducers of endothelial cell apoptosis in pulmonary arterial hypertension?  

PubMed

Endothelial cell (EC) apoptosis seems to play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). We aimed to test the hypothesis that circulating anti-endothelial cell antibodies (AECA) of PAH patients induce EC apoptosis. Immunoglobulin (Ig)G was purified from sera of PAH patients (n?=?26), patients with systemic lupus erythematosus (SLE) nephritis without PAH (n?=?16), patients with systemic sclerosis (SSc) without PAH (n?=?58) and healthy controls (n?=?14). Human umbilical vein endothelial cells (HUVECs) were incubated with patient or healthy control IgG for 24?h. Thereafter, apoptosis was quantified by annexin A5 binding and hypoploid cell enumeration by flow cytometry. Furthermore, real-time cell electronic sensing (RT-CES™) technology was used to monitor the effects of purified IgG from patient and healthy control IgG on HUVECs. As demonstrated previously, IgG of AECA-positive SLE nephritis patients (n?=?7) induced a higher percentage of apoptosis of HUVECs compared to IgG of AECA-negative SLE nephritis patients and healthy controls. Furthermore, IgG of AECA-positive SLE nephritis patients induced a marked decrease in cell index as assessed by RT-CES™ technology. IgG of AECA-positive PAH patients (n?=?12) and SSc patients (n?=?13) did not alter the percentage of HUVEC apoptosis or cell index compared to IgG of AECA-negative PAH and SSc patients and healthy controls. AECA-positive PAH patients, in contrast to SLE nephritis patients, do not have circulating IgG AECA that enhances apoptosis of HUVECs?in vitro. Further studies should focus on other mechanisms by which AECA may enhance EC apoptosis in PAH, such as antibody-dependent cell-mediated cytotoxicity. PMID:23815467

Arends, S J; Damoiseaux, J G M C; Duijvestijn, A M; Debrus-Palmans, L; Vroomen, M; Boomars, K A; Brunner-La Rocca, H-P; Reutelingsperger, C P M; Cohen Tervaert, J W; van Paassen, P

2013-12-01

252

The Microbead Occlusion Model: A Paradigm for Induced Ocular Hypertension in Rats and Mice  

PubMed Central

Purpose. Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Animal models often involve techniques for IOP elevation that are surgically invasive. Here the authors describe a novel and relatively simple method for inducing a highly consistent, modest, and repeatable elevation in IOP for rats and mice. Methods. IOP was elevated unilaterally by injection of polystyrene microbeads into the anterior chamber to occlude aqueous outflow in rats (2.5–7 ?L) and mice (1 ?L). The fellow eye received an equivalent saline injection as internal control. The authors used tonometry to measure microbead-induced IOP elevations. Optic nerves were processed histologically to determine axon loss. Results. For rats, a single injection of microbeads raised IOP by 21% to 34%, depending on volume, for approximately 2 weeks, though they were not tracked to full recovery. IOP in the saline-injected eye was constant. An additional injection (5 ?L) extended the elevation to 8 weeks. Cumulative pressure exposure for both injections increased linearly. For mice, a single 1-?L injection of microbeads elicited a highly regular 30% elevation in IOP that persisted for more than 3 weeks, with a linear rise in cumulative pressure exposure. For both rats and mice, interanimal variability on a given day was modest, approximately 5% of the mean IOP measurement. Extended elevations (4–5 weeks) induced approximately a 20% loss of axons in both rats and mice. Conclusions. These data support a novel and flexible model of modest ocular hypertension with axon loss. The maximal duration of IOP elevation will be further characterized in future studies.

Sappington, Rebecca M.; Carlson, Brian J.; Crish, Samuel D.

2010-01-01

253

Glycyrrhizin could reduce ocular hypertension induced by triamcinolone acetonide in rabbits  

PubMed Central

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.

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

2011-01-01

254

Pyrrolidine Dithiocarbamate Restores Endothelial Cell Membrane Integrity and Attenuates Monocrotaline-Induced Pulmonary Artery Hypertension  

PubMed Central

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-?B 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 day 1, 3 and 14 × 2 wks) an inhibitor of inflammation and NF-?B activation. Hemodynamic data, the expression of inhibitory (I)-?B?, caveolin-1 and Tie2 (a membrane protein), activation of PY-STAT3 and NF-?B, and superoxide chemiluminescence were examined. Rats developed progressive PAH at 2 wks post-MCT. There were progressive reduction in the expression of caveolin-1, Tie2 and activation of PY-STAT3 in the lungs. Reduction in I-?B? expression was present at 2 and 4 wks post-MCT. Superoxide chemiluminescence and NF-?B activation were observed only at 2 wks post-MCT and both decreased by 4 wks post-MCT despite progressive PAH. PDTC (starting on day 1 and 3) rescued caveolin-1 and Tie2, reversed MCT-induced PY-STAT3 activation, and attenuated PAH. In addition, PDTC restored I-?B? expression and reduced superoxide chemiluminescence at 2 wks, but did not inhibit NF-?B activation despite attenuation of PAH. PDTC had no effect on established PAH. Increased superoxide chemiluminescence and NF-?B activation appear to be a transient phenomenon in the MCT model. Thus, the disruption of endothelial cell membrane integrity resulting in cav-1 loss and reciprocal activation of PY-STAT3 plays a key role in the MCT-induced PAH.

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

2008-01-01

255

Mutant Human Myocilin Induces Strain Specific Differences in Ocular Hypertension and Optic Nerve Damage in Mice  

PubMed Central

Elevated intraocular pressure (IOP) is a causative risk factor for the development and progression of glaucoma. Glaucomatous mutations in myocilin (MYOC) damage the trabecular meshwork and elevate IOP in humans and in mice. Animal models of glaucoma are important to discover and better understand molecular pathogenic pathways and to test new glaucoma therapeutics. Although a number of different animal models of glaucoma have been developed and characterized, there are no true models of human primary open angle glaucoma (POAG). The overall goal of this work is to develop the first inducible mouse model of POAG using a human POAG relevant transgene (i.e. mutant MYOC) expression in mouse eyes to elevate IOP and cause pressure induced damage to the optic nerve. Four mouse strains (A/J, BALB/cJ, C57BL/6J, and C3H/HeJ) were used in this study. Ad5.MYOC.Y437H (5 × 107 pfu) was injected intravitreally into one eye, with the uninjected contralateral eye serving as the control eye. Conscious IOP measurements were taken using a TonoLab rebound tonometer. Optic nerve damage was determined by scoring PPD stained optic nerve cross sections. Retinal ganglion cell and superior colliculus damage was assessed by Nissl stain cell counts. Intravitreal administration of viral vector Ad5.MYOC.Y437H caused a prolonged, reproducible, and statistically significant IOP elevation in BALB/cJ, A/J, and C57BL/6J mice. IOPs increased to approximately 25 mm Hg for 8 weeks (p<0.0001). In contrast, the C3H/HeJ mouse strain was resistant to Ad5.MYOC.Y437H induced IOP elevation for the 8-week time period. IOPs were stable (12–15 mm Hg) in the uninjected control eyes. We also determined whether there were any strain differences in pressure-induced optic nerve damage. Even though IOP was similarly elevated in three of the strains tested (BALB/cJ, C57BL/6J, and A/J ) only the A/J strain had considerable and significant optic nerve damage at the end of 8 weeks with optic nerve damage score of 2.64 +/? 0.19 (n=18, p<0.001) in the injected eye. There was no statistical difference in retinal ganglion cell death or superior colliculus damage at the 8-week time point in any of the strains tested. These results demonstrate strain dependent responses to Ad5.MYOC.Y437H-induced ocular hypertension and pressure-induced optic nerve damage.

McDowell, Colleen M.; Luan, Tomi; Zhang, Zhang; Putliwala, Tasneem; Wordinger, Robert J.; Millar, J. Cameron; John, Simon W.M.; Pang, Iok-Hou; Clark, Abbot F.

2012-01-01

256

Mutant human myocilin induces strain specific differences in ocular hypertension and optic nerve damage in mice.  

PubMed

Elevated intraocular pressure (IOP) is a causative risk factor for the development and progression of glaucoma. Glaucomatous mutations in myocilin (MYOC) damage the trabecular meshwork and elevate IOP in humans and in mice. Animal models of glaucoma are important to discover and better understand molecular pathogenic pathways and to test new glaucoma therapeutics. Although a number of different animal models of glaucoma have been developed and characterized, there are no true models of human primary open angle glaucoma (POAG). The overall goal of this work is to develop the first inducible mouse model of POAG using a human POAG relevant transgene (i.e. mutant MYOC) expression in mouse eyes to elevate IOP and cause pressure-induced damage to the optic nerve. Four mouse strains (A/J, BALB/cJ, C57BL/6J, and C3H/HeJ) were used in this study. Ad5.MYOC.Y437H (5 × 10(7) pfu) was injected intravitreally into one eye, with the uninjected contralateral eye serving as the control eye. Conscious IOP measurements were taken using a TonoLab rebound tonometer. Optic nerve damage was determined by scoring PPD stained optic nerve cross sections. Retinal ganglion cell and superior colliculus damage was assessed by Nissl stain cell counts. Intravitreal administration of viral vector Ad5.MYOC.Y437H caused a prolonged, reproducible, and statistically significant IOP elevation in BALB/cJ, A/J, and C57BL/6J mice. IOPs increased to approximately 25 mm Hg for 8 weeks (p < 0.0001). In contrast, the C3H/HeJ mouse strain was resistant to Ad5.MYOC.Y437H induced IOP elevation for the 8-week time period. IOPs were stable (12-15 mm Hg) in the uninjected control eyes. We also determined whether there were any strain differences in pressure-induced optic nerve damage. Even though IOP was similarly elevated in three of the strains tested (BALB/cJ, C57BL/6J, and A/J) only the A/J strain had considerable and significant optic nerve damage at the end of 8 weeks with optic nerve damage score of 2.64 ± 0.19 (n = 18, p < 0.001) in the injected eye. There was no statistical difference in retinal ganglion cell death or superior colliculus damage at the 8-week time point in any of the strains tested. These results demonstrate strain dependent responses to Ad5.MYOC.Y437H-induced ocular hypertension and pressure-induced optic nerve damage. PMID:22575566

McDowell, Colleen M; Luan, Tomi; Zhang, Zhang; Putliwala, Tasneem; Wordinger, Robert J; Millar, J Cameron; John, Simon W M; Pang, Iok-Hou; Clark, Abbot F

2012-05-03

257

Pressure induced cellular senescence-a possible mechanism linking venous hypertension to venous ulcers  

Microsoft Academic Search

Introduction: Slowed healing and venous ulcers are the soft tissue effects of chronic venous insufficiency (CVI). Chronic venous hypertension has long been thought to be the root cause of these soft tissue effects, but mechanisms linking venous hypertension to delayed wound healing have been elusive. Dermal fibroblasts isolated from venous ulcers have morphologies and protein production suggestive of premature aging.

N. Fernandez; K. M. Lounsbury; T. Osler; K. A. Corrow; C. Healey; P. Forgione; A. C. Stanley

2003-01-01

258

Low ethanol intake prevents salt-induced hypertension in WKY rats  

Microsoft Academic Search

Low alcohol intake in humans lowers the risk of coronary heart disease and may lower blood pressure. In hypertension, insulin resistance with altered glucose metabolism leads to increased formation of aldehydes. We have shown that chronic low alcohol intake decreased systolic blood pressure (SBP) and tissue aldehyde conjugates in spontaneously hypertensive rats and demonstrated a strong link between elevated tissue

Sudesh Vasdev; Vicki Gill; Sushil Parai; Veeresh Gadag

2006-01-01

259

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

Microsoft Academic Search

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

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

2011-01-01

260

Role of CYP450 metabolites of arachidonic acid during pregnancy induced hypertension in rats  

Microsoft Academic Search

We have reported that chronic reductions in uterine perfusion pressure in pregnant rats lead to a hypertensive state closely resembles preeclampsia in women. The increased arterial pressure in these rats is associated with renal vasoconstriction, proteinuria and endothelial dysfunction. Alterations in renal metabolism of CYP450 metabolites of arachidonic have been reported in different models of hypertension and in women with

Maria T. Llinas; Barbara T. Alexander; Maria F. Capparelli; Mairead A. Carroll; Joey P. Granger

2002-01-01

261

Beneficial effects of combination of valsartan and amlodipine on salt-induced brain injury in hypertensive rats.  

PubMed

The optimum antihypertensive treatment for prevention of hypertensive stroke has yet to be elucidated. This study was undertaken to examine the benefit of a combination of valsartan, an angiotensin II type 1 (AT1) receptor blocker, and amlodipine, a calcium channel blocker, in prevention of high-salt-induced brain injury in hypertensive rats. High-salt-loaded stroke-prone spontaneously hypertensive rats (SHRSPs) were given 1) vehicle, 2) valsartan (2 mg/kg/day), 3) amlodipine (2 mg/kg/day), or 4) a combination of valsartan and amlodipine for 4 weeks. The effects on brain injury were compared between all groups. High-salt loading in SHRSPs caused the reduction of cerebral blood flow (CBF), cerebral hypoxia, white matter lesions, glial activation, AT1 receptor up-regulation, endothelial nitric-oxide synthase (eNOS) uncoupling, inducible nitric-oxide synthase induction, and nitroxidative stress. Valsartan, independently of blood pressure, enhanced the protective effects of amlodipine against brain injury, white matter lesions, and glial activation in salt-loaded SHRSPs. These beneficial effects of valsartan added to amlodipine were associated with an additive improvement in CBF and brain hypoxia because of an additive improvement in cerebral arteriolar remodeling and vascular endothelial dysfunction. Furthermore, valsartan added to amlodipine enhanced the attenuation of cerebral nitroxidative stress through an additive suppression of eNOS uncoupling. Valsartan, independently of blood pressure, augmented the protective effects of amlodipine against brain injury in salt-loaded hypertensive rats through an improvement in brain circulation attributed to nitroxidative stress. Our results suggest that the combination of valsartan and amlodipine may be a promising strategy for the prevention of salt-related brain injury in hypertensive patients. PMID:21807884

Dong, Yi-Fei; Kataoka, Keiichiro; Tokutomi, Yoshiko; Nako, Hisato; Nakamura, Taishi; Toyama, Kensuke; Sueta, Daisuke; Koibuchi, Nobutaka; Yamamoto, Eiichiro; Ogawa, Hisao; Kim-Mitsuyama, Shokei

2011-08-01

262

2,3?,4,5?-Tetramethoxystilbene prevents deoxycorticosterone-salt-induced hypertension: contribution of cytochrome P-450 1B1  

PubMed Central

Reactive oxygen species (ROS) contribute to various models of hypertension, including deoxycorticosterone acetate (DOCA)-salt-induced hypertension. Recently, we have shown that ROS, generated by cytochrome P-450 1B1 (CYP1B1) from arachidonic acid, mediate vascular smooth muscle cell growth caused by angiotensin II. This study was conducted to determine the contribution of CYP1B1 to hypertension and associated pathophysiological changes produced by DOCA (30 mg/kg) given subcutaneously per week with 1% NaCl + 0.1% KCl in drinking water to uninephrectomized rats for 6 wk. DOCA-salt treatment increased systolic blood pressure (SBP). Injections of the selective inhibitor of CYP1B1, 2,3?,4,5?-tetramethoxystilbene (TMS; 300 ?g/kg ip every 3rd day) initiated at the 4th week of DOCA-salt treatment normalized SBP and decreased CYP1B1 activity but not its expression in the aorta, heart, and kidney. TMS also inhibited cardiovascular and kidney hypertrophy, prevented the increase in vascular reactivity and endothelial dysfunction, and minimized the increase in urinary protein and K+ output and the decrease in urine osmolality, Na+ output, and creatinine clearance associated with DOCA-salt treatment. These pathophysiological changes caused by DOCA-salt treatment and associated increase in vascular superoxide production, NADPH oxidase activity, and expression of NOX-1, and ERK1/2 and p38 MAPK activities in the aorta, heart, and kidney were inhibited by TMS. These data suggest that CYP1B1 contributes to DOCA-salt-induced hypertension and associated pathophysiological changes, most likely as a result of increased ROS production and ERK1/2 and p38 MAPK activity, and could serve as a novel target for the development of agents like TMS to treat hypertension.

Sahan-Firat, Seyhan; Jennings, Brett L.; Yaghini, Fariborz A.; Song, Chi Young; Estes, Anne M.; Fang, Xiao R.; Farjana, Nasreen; Khan, Amir I.

2010-01-01

263

DA8159, a potent cGMP phosphodiesterase inhibitor, attenuates monocrotaline-induced pulmonary hypertension in rats  

Microsoft Academic Search

In this study, we evaluated the effects of oral administration of DA-8159, a selective phosphodiesterase-5 inhibitor, on the\\u000a development of pulmonary hypertension (PH) induced by monocrotaline (MCT). Rats were administered either MCT (60 mg\\/kg) or\\u000a saline. MCT-treated rats were divided into three groups and received orally administered vehicle, or 1 mg\\/kg or 5 mg\\/kg of\\u000a DA-8159, twice a day for

Kyung Koo Kang; Gook Jun Ahn; Yong Sung Sohn; Byoung Ok Ahn; Won Bae Kim

2003-01-01

264

Effect of Chronic Dietary Treatment with Nicotinic Acid on the Development and Maintenance of Deoxycorticosterone-Acetate-Salt-Induced Hypertension  

Microsoft Academic Search

Chronic dietary administration of either \\/-tryptophan (5.0%) or nicotinic acid (5.0%) reduced the elevated blood pressure of rats with established, deoxycorticosterone-acetate (DOCA)-salt-induced hypertension without affecting either body weight or cardiac hypertrophy. In a second study, chronic dietary administration of nicotinic acid (2.5 and 5.0%) provided significant protection against the development of an elevated blood pressure in rats treated with DOCA

Melvin J. Fregly; Ora E. Lockley; Jose L. Torres; Robert Cade

1988-01-01

265

Cold-restraint induced gastric lesions in normotensive and spontaneously hypertensive rats  

SciTech Connect

Spontaneously hypertensive (SHR) rats and normotensive Wistar-Kyoto (WKY) rats were subjected to 2 hr of cold-restraint stress at 4-6/sup o/C following a 24 hr fast. WKY rats had a significantly greater incidence and degree of ulceration of the gastric glandular mucosa than did SHR rats. Mean arterial pressure, obtained from a chronic arterial cannula, fell during 2 hr of cold-restraint stress in both SHR and WKY rats. Heart rate was unchanged in WKY but fell significantly in SHR. Plasma norepinephrine (NE) and epinephrine (E), determined by radioenzymatic assay, increased significantly following stress. Increased levels of NE remained similar for both SHR and WKY rats, while post-stress levels of E for the SHR rats greatly exceeded E levels for WKY rats. A greater degree of hypothermia was also noted in SHR rats. Decreased stress induced ulcerogenesis in the SHR may be due to the well-known altered hemodynamic and autonomic nervous system reactivity in this strain or other factors not yet discovered.

Athey, G.R.; Iams, S.G.

1981-02-23

266

Pulmonary hypertension induced in dogs by hypoxia at different high-altitude levels.  

PubMed

Chronic natural hypoxia at 2300 m altitude induces mild pulmonary hypertension (PH) in healthy dogs. The influence of more severe hypoxia on the same group of dogs was evaluated by re-examining such dogs at 3500 m, after they had regularly exercised at this altitude level for half a year. Despite severe hypoxaemia at 3500 m (PaO2 52+/-5 mmHg), none of the dogs developed erythrocytosis, and their PCV at 3500 m (48% +/- 4%) did not differ from that at 2300 m (49% +/- 4%). There was a tendency towards an elevated systemic BP, with a significant increase in diastolic BP (105 +/- 13 mmHg at 3500 m versus 98 +/- 17 at 2300 m). Tricuspid regurgitation (TR) was detected in 7 dogs at 3500 m compared to 8 dogs at 2300 m. The mean TR Vmax was significantly higher at 3500 m, and all 7 dogs had systolic PH at 3500 m (33.6-54.8 mmHg), when PH was defined as TR Vmax > or = 2.8 m/s, i.e. a peak pressure gradient > 30 mmHg. Hence, in dogs, increasing altitude and the concomitant hypoxia result in a progressively more pronounced PH and an elevated systemic BP. Intermittent severe hypoxaemia of around 50 mmHg may not cause erythrocytosis in healthy dogs, even over a prolonged period. PMID:14672455

Glaus, T M; Hässig, M; Baumgartner, C; Reusch, C E

2003-12-01

267

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

PubMed Central

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.

Borras, Teresa

2011-01-01

268

Carotid body denervation prevents the development of insulin resistance and hypertension induced by hypercaloric diets.  

PubMed

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

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

2013-03-25

269

Rhodiola-Water Extract Induces ?-endorphin Secretion to Lower Blood Pressure in Spontaneously Hypertensive Rats.  

PubMed

Rhodiola rosea (Rhodiola) is grown at high altitudes and northern latitudes. It is mainly used clinically as an adaptogen, but antihypertensive effects have been reported for the extract. These have not been well investigated, so in the present study, we evaluated the effect of Rhodiola-water extract on blood pressure in spontaneously hypertensive rats (SHRs) and investigated the potential mechanism(s) for this action. In conscious male SHRs, systolic blood pressure (SBP) and heart rate were recorded using the tail-cuff method. Plasma ?-endorphin was measured by enzyme-linked immunosorbent assay. Rhodiola-water extract decreased SBP in SHRs in a dose-dependent manner, and this action was more significant than that in normal group named Wistar-Kyoto (WKY) rats. This reduction of SBP in SHRs was inhibited by pretreatment with the selective opioid ?-receptor antagonist, cyprodime, but not by naloxonazine, an antagonist specific to opioid ?1-receptor. Also, the SBP-lowering action of Rhodiola-water extract was attenuated in adrenalectomized SHRs. Moreover, Rhodiola-water extract dose-dependently increased ?-endorphin release in SHRs, and the elevation of ?-endorphin in SHRs was higher than that in WKY. Thus, we suggest that Rhodiola-water extract can induce release of ?-endorphin to lower SBP in SHRs. Copyright © 2012 John Wiley & Sons, Ltd. PMID:23192943

Lee, Wei-Jing; Chung, Hsien-Hui; Cheng, Yung-Ze; Lin, Hung Jung; Cheng, Juei-Tang

2012-11-28

270

Reduced Adrenomedullin Expression in Gastric Mucosa of Portal Hypertensive Rats After Ethanol-Induced Injury  

PubMed Central

Objective To determine the expression and localization of adrenomedullin (AM) and its receptor (AM-R) in portal hypertensive (PHT) gastric mucosa after intragastric ethanol administration. Summary Background Data The repair of gastric mucosal injury requires reestablishment of the microvascular network. The authors previously demonstrated impaired angiogenesis of PHT gastric mucosa after ethanol-induced injury. Because AM, a potent vasodilatory peptide, is also a novel growth and angiogenic factor, the authors hypothesized that AM is involved in the impaired repair of PHT gastric mucosa and its microvasculature after damage. Methods Either PHT or sham-operated rats received intragastrically 100% ethanol, and the stomachs were excised at 1, 6, and 24 hours later. Expression and localization of AM and AM-R mRNA were examined by competitive reverse transcription–polymerase chain reaction and in situ hybridization. AM protein expression was examined by Western blot analysis. Results One hour after ethanol administration, AM mRNA expression in PHT gastric mucosa was significantly decreased by 81%, especially in the superficial mucosa, compared with the gastric mucosa in sham-operated rats. The significant decrease lasted for 24 hours. AM protein expression was significantly decreased by 43% compared with the sham-operated gastric mucosa. Although AM-R mRNA expression in both groups was significantly increased 1 hour after ethanol administration and lasted for 24 hours compared with baseline, there were no differences between the two groups. Conclusions The expression of AM in PHT gastric mucosa after ethanol-induced injury is significantly decreased compared with controls. This finding could explain one mechanism for the impaired angiogenesis after injury of PHT gastric mucosa.

Tomikawa, Morimasa; Wang, Hongtao; Jones, Michael K.; Sugimachi, Keizo; Sarfeh, I. James; Tarnawski, Andrzej S.

1999-01-01

271

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

PubMed Central

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.

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

2004-01-01

272

Endogenous Estrogen Attenuates Hypoxia-Induced Pulmonary Hypertension by Inhibiting Pulmonary Arterial Vasoconstriction and Pulmonary Arterial Smooth Muscle Cells Proliferation  

PubMed Central

Exogenous estrogen was shown to exert various beneficial effects on multiple diseases including hypoxia-induced pulmonary hypertension (HPH). However, the effect of endogenous estrogen on HPH was seldom investigated. In the present study, we explored the protective effects and mechanisms of endogenous estrogen on hypoxia-induced pulmonary hypertension. Male, female, pregnant and ovariectomized rats were housed in a hypoxic condition for 21 days, and then hemodynamic together with morphologic indexes of pulmonary circulation were measured. The right ventricular systolic pressure, mean pulmonary artery pressure, right ventricular hypertrophy index, and arterial remodeling index were significantly elevated after chronic hypoxia exposure. Experimental data showed less severity in female, especially in pregnant rats. In vitro, artery rings of different sex or estrus cycle rats were obtained, and then artery rings experiments were performed to investigate pulmonary vasoconstriction by recording the maximum phase II vasoconstriction. Data showed that the vasoconstriction was milder in proestrus female than diestrus female or male groups, which could be leveled by treating U0126 (a MAPK pathway inhibitor). Pulmonary arterial smooth muscle cells isolated from different sex or estrus cycle rats were cultured in the condition of 2% oxygen for 24 hours, and cell proliferation was evaluated by the [3H]-thymidine incorporation assay. Cells from proestrus rats exhibited lower proliferation than the other groups, which could be countered by both U0126 and raloxifene (a selective estrogen receptor modulator). Serum estradiol levels were detected, and rats with higher levels showed less severity of pulmonary hypertension. Conclusively, endogenous estrogen may alleviate hypoxia-induced pulmonary hypertension by attenuating vasoconstriction through non-genomic mechanisms and inhibiting smooth muscle cells proliferation through both genomic and non-genomic mechanisms.

Xu, Dunquan; Niu, Wen; Luo, Ying; Zhang, Bo; Liu, Manling; Dong, Haiying; Liu, Yi; Li, Zhichao

2013-01-01

273

Role of copper transport protein Antioxidant-1 in Angiotensin II-induced hypertension: A key regulator of Extracellular SOD  

PubMed Central

Extracellular superoxide dismutase (SOD3) is a secretory copper enzyme involved in protecting angiotensin II (Ang II)-induced hypertension. We previously found that Ang II upregulates SOD3 expression and activity as a counter-regulatory mechanism; however, underlying mechanisms are unclear. Antioxidant-1 (Atox1) is shown to act as a copper-dependent transcription factor as well as copper chaperone for SOD3 in vitro, but its role in Ang II-induced hypertension in vivo is unknown. Here we show that Ang II infusion increases Atox1 expression as well as SOD3 expression and activity in aortas of wild-type mice, which are inhibited in mice lacking Atox1. Accordingly, Ang II increases vascular O2•? production, reduces endothelium-dependent vasodilation and increases vasoconstriction in mesenteric arterioles to a greater extent in Atox1?/? than in wild-type mice. This contributes to augmented hypertensive response to Ang II in Atox1?/? mice. In cultured vascular smooth muscle cells, Ang II promotes translocation of Atox1 to the nucleus, thereby increasing SOD3 transcription by binding to Atox1 responsive element in the SOD3 promoter. Furthermore, Ang II increases Atox1 binding to the copper exporter ATP7A which obtains copper from Atox1 as well as translocation of ATP7A to plasma membranes where it colocalizes with SOD3. As its consequence, Ang II decreases vascular copper levels, which is inhibited in Atox1?/? mice. In summary, Atox1 functions to prevent Ang II-induced endothelial dysfunction and hyper-contraction in resistant vessels as well as hypertension in vivo by reducing extracellular O2•? levels via increasing vascular SOD3 expression and activity.

Ozumi, Kiyoshi; Sudhahar, Varadarajan; Kim, Ha Won; Chen, Gin-Fu; Kohno, Takashi; Finney, Lydia; Vogt, Stefan; McKinney, Ronald D.; Ushio-Fukai, Masuko; Fukai, Tohru

2012-01-01

274

Disulfiram Induced Reversible Hypertension: A Prospective Case Study and Brief Review  

PubMed Central

Disulfiram (DSF) is one of the recommended aids in the management of alcohol dependence. Hypertension may be a clinically significant, dose-dependent, and usually reversible adverse event of DSF therapy. We report 6 month prospective study of normotensive case of comorbid alcohol and tobacco dependence that developed reversible stage-II hypertension within 2-4 weeks of DSF therapy. We suggest that regular monitoring of blood pressure at least fortnightly for 1st 3 months, followed by monthly for next 3 months, and later once in 3 months, may possibly detect “silent” adverse event of DSF – hypertension.

Kulkarni, Ranganath R.; Bairy, Bhavya K.

2013-01-01

275

Obesity-induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins*  

PubMed Central

Excess weight gain contributes to increased blood pressure in most patients with essential hypertension. Although the mechanisms of obesity hypertension are not fully understood, increased renal sodium reabsorption and impaired pressure natriuresis play key roles. Several mechanisms contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system, which appears to be mediated in part by increased levels of the adipocyte-derived hormone leptin, stimulation of pro-opiomelanocortin neurons, and subsequent activation of central nervous system melanocortin 4 receptors.

Hall, John E.; da Silva, Alexandre A.; do Carmo, Jussara M.; Dubinion, John; Hamza, Shereen; Munusamy, Shankar; Smith, Grant; Stec, David E.

2010-01-01

276

Sarcoidosis-induced pericarditis in a patient with portopulmonary hypertension: a case report  

PubMed Central

Portopulmonary hypertension is a rare and severe complication of patients with cirrhosis. Sarcoidosis, a disease of unknown etiology, is also a cause of pulonary hypertension and right heart dysfunction. We report the case of a 51-year-old male patient, suffering from cirrhosis due to Wilson’s disease, portal hypertension and pulmonary hypertension (PH), who developed severe pericarditis. Wilson’s disease was diagnosed 8 years before his last admission to our hospital and was being successfully treated with D-penicillamine. PH was recognized 2 years before admission and being treated with bosentan. The patient complained for dyspnea at rest and the 2D echocardiogram revealed a significant amount of pericardial fluid. All other causes of acute pericarditis were excluded and his laboratory, imaging and histopathological investigation showed evidence of sarcoidosis. He underwent a therapy with corticosteroids (methylprednisolone) and his follow-up examination showed remarkable decrease of the levels of mean pulmonary artery pressure and pericardial fluid.

Giouleme, Olga; Patsiaoura, Kalliopi; Vasiliadis, Themistoklis; Grammatikos, Nikolaos; Kakavas, Nikitas; Mpoumponaris, Alexander; Eugenidis, Nikolaos; Basayannis, Elias

2009-01-01

277

Sarcoidosis-induced pericarditis in a patient with portopulmonary hypertension: a case report.  

PubMed

Portopulmonary hypertension is a rare and severe complication of patients with cirrhosis. Sarcoidosis, a disease of unknown etiology, is also a cause of pulonary hypertension and right heart dysfunction. We report the case of a 51-year-old male patient, suffering from cirrhosis due to Wilson's disease, portal hypertension and pulmonary hypertension (PH), who developed severe pericarditis. Wilson's disease was diagnosed 8 years before his last admission to our hospital and was being successfully treated with D-penicillamine. PH was recognized 2 years before admission and being treated with bosentan. The patient complained for dyspnea at rest and the 2D echocardiogram revealed a significant amount of pericardial fluid. All other causes of acute pericarditis were excluded and his laboratory, imaging and histopathological investigation showed evidence of sarcoidosis. He underwent a therapy with corticosteroids (methylprednisolone) and his follow-up examination showed remarkable decrease of the levels of mean pulmonary artery pressure and pericardial fluid. PMID:19918393

Giouleme, Olga; Anagnostis, Panagiotis; Patsiaoura, Kalliopi; Vasiliadis, Themistoklis; Grammatikos, Nikolaos; Kakavas, Nikitas; Mpoumponaris, Alexander; Eugenidis, Nikolaos; Basayannis, Elias

2009-08-18

278

Prostaglandin E1 selectively reduces group B beta-hemolytic streptococci-induced pulmonary hypertension in newborn piglets.  

PubMed

Group B beta-hemolytic streptococci (GBS)-induced pulmonary hypertension was generated in ten newborn piglets. Intravenous infusions of either prostaglandin E1 (PGE1) (n = 5) or placebo (n = 5) were begun after 60 minutes of stable pulmonary hypertension. The effects of these interventions on cardiopulmonary hemodynamics were studied. Pulmonary artery pressure (PAP) increased similarly in both groups during the first 60 minutes of GBS infusion. By two hours after intervention, PAP was significantly lower in the animals given PGE1 (20 +/- 4 vs 32 +/- 5 mm Hg for PGE1 vs placebo). The ratio of pulmonary to systemic vascular resistance followed a pattern analogous to PAP, increasing with the GBS infusion, indicating selective pulmonary vasoconstriction. The pulmonary vascular resistance/systemic vascular resistance ratio decreased after intervention in the group given PGE1 only (0.25 +/- 0.08 vs 0.50 +/- 0.12 for PGE1 vs placebo), indicating selective pulmonary vasodilation. Transient systemic hypotension was noted at one hour after initiation of PGE1 infusion. Prostaglandin E1 infusion selectively improved GBS-induced pulmonary hypertension and hypoxemia in newborn piglets with only transient systemic hypotension. PMID:2492755

Hammerman, C; Aramburo, M J; Choi, J H

1989-03-01

279

Blood volume increase in salt-induced pulmonary hypertension, heart failure and ascites in broiler and White Leghorn chickens.  

PubMed Central

In this study we tested the hypothesis that excess dietary salt produces an expansion of extracellular fluid volume which may be associated with pulmonary hypertension-induced right ventricular failure in chickens with rapid growth rates. One-week-old broiler and White Leghorn chickens were given 0.5% salt in their drinking water for three weeks. Saline water had a minimal effect on White Leghorns. The hypothesis appears to be correct since salt-treatment in broilers resulted in up to 30% expansion in blood volume and there was 50% mortality from pulmonary hypertension-induced right ventricular failure and ascites. There was marked (up to 88% in some broilers) right ventricular hypertrophy, an indicator of pulmonary hypertension. There was less left ventricular hypertrophy as shown by an increase in the ratio of the right to total ventricle weight. There was up to 32% decrease in growth rate. There was renal hypertrophy in the salt-treated birds as shown by a higher kidney to body weight ratio.

Mirsalimi, S M; O'Brien, P J; Julian, R J

1993-01-01

280

TRPV1 activation prevents high-salt diet-induced nocturnal hypertension in mice  

Microsoft Academic Search

High dietary salt-caused hypertension is associated with increasing reactive oxygen species generation and reduced nitric\\u000a oxide (NO) bioavailability. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, is proposed\\u000a to be involved in Dahl salt-sensitive hypertension, as determined in acute or short-term experiments. However, it remains\\u000a unknown whether activation of TRPV1 by dietary capsaicin could prevent the

Xinzhong Hao; Jing Chen; Zhidan Luo; Hongbo He; Hao Yu; Liqun Ma; Shuangtao Ma; Tianqi Zhu; Daoyan Liu; Zhiming Zhu

2011-01-01

281

Immunosuppression Improves Blood Pressure and Endothelial Function in a Rat Model of Pregnancy-Induced Hypertension  

Microsoft Academic Search

BackgroundHypertensive disorders of pregnancy, including preeclampsia (PE), affect ~7–10% of pregnancies in the US. Clinical and experimental studies strongly suggest that the maternal immune system plays a role in the development of these disorders; however, few therapeutic options exist aside from delivery.MethodsUsing a deoxycorticosterone acetate (DOCA)\\/salt-low renin rat model, which exhibits hypertension, proteinuria, endothelial dysfunction, and intrauterine growth restriction (IUGR),

John H. Tinsley; Valorie L. Chiasson; Sanique South; Ashutosh Mahajan; Brett M. Mitchell

2009-01-01

282

Role of Reactive Oxygen Species in Chronic Hypoxia-Induced Pulmonary Hypertension and Vascular Remodeling  

Microsoft Academic Search

\\u000a Pulmonary hypertension is a life-threatening disease process that affects adults and children. Pediatric patients with lung\\u000a diseases that can be complicated by alveolar hypoxia, such as bronchopulmonary dysplasia (BPD), are at risk for developing\\u000a pulmonary hypertension, which leads to right heart failure and greatly increases morbidity and mortality. We review the evidence\\u000a that reactive oxygen species (ROS) are generated by

Eva Nozik-Grayck; Kurt R. Stenmark

283

Individual and concomitant effects of cardioprotective programs on cardiac apelinergic system and oxidative state in L-NAME-induced hypertension.  

PubMed

The effect of aerobic training and Ferula gummosa supplementation (90 mg/kg) on apelinergic system and markers of cardiac stress in hypertensive rats were studied. Chronically administered l-NAME resulted in an increased level of angiotensin-converting enzyme (ACE), malondialdehyde (MDA), and high-sensitive C-reactive protein (hs-CRP), and also reduced the levels of apelin, apelin and its receptor (APJ), and nitric oxide (NO) and the total antioxidant capacity (TAC), when compared with the control group. The combination of aerobic exercise and Ferula gummosa decreased MDA and hs-CRP and significantly increased cardiac apelinergic system, NO, and TAC, when compared with the control and the l-NAME groups. A rationale for an inhibitory role and a cardioprotective effect of aerobic exercise training in the attenuation of hypertension-induced cardiotoxicity was developed. PMID:22578103

Mahmoody, Seeyed Ali Akbar; Gharakhanlou, Reza; Roshan, Valiollah Dabidi; Hedayati, Mehdi

2012-05-11

284

N-acetylcysteine antagonizes the development but does not reverse ACTH-induced hypertension in the rat.  

PubMed

We investigated the effect of antioxidant N-acetylcysteine (NAC) on adrenocorticotropic hormone (ACTH)-hypertension. Male Sprague-Dawley rats received NAC (10 mg/L) or water 4 days before ACTH/saline treatment for 13 days (prevention study). In a reversal study, NAC commenced on day 8 of ACTH/saline treatment and continued for 5 days. ACTH increased systolic blood pressure (SBP) in water drinking rats (111 +/- 1 to 131 +/- 3 mmHg, p < 0.001). In the prevention study, NAC + ACTH increased SBP (108 +/- 2 to 120 +/- 2 mmHg, p < 0.001) but less than ACTH alone (p' < 0.05). In the reversal study, NAC had no significant effect (132 +/- 4 to 124 +/- 3 mmHg, ns). Thus, NAC partially prevented but did not reverse ACTH-induced hypertension. PMID:16546835

Mondo, Charles K; Zhang, Yi; de Macedo Possamai, Vinicius; Miao, Yuchun; Schyvens, Christopher G; McKenzie, Katja U S; Hu, Lexian; Guo, Zhijun; Whitworth, Judith A

2006-02-01

285

Estrogen receptor-? in the paraventricular nucleus and rostroventrolateral medulla plays an essential protective role in aldosterone/salt-induced hypertension in female rats.  

PubMed

The identification of the specific estrogen receptor (ER) subtypes that are involved in estrogen protection from hypertension and their specific locations in the central nervous system is critical to our understanding and design of effective estrogen replacement therapies in women. Using selective ER agonists and recombinant adeno-associated virus (AAV) carrying small interference (si) RNA to silence either ER? (AAV-siRNA-ER?) or ER? (AAV-siRNA-ER?), the present study investigated regional specificity of different ER subtypes in the protective actions of estrogen in aldosterone (Aldo)-induced hypertension. Intracerebroventricular infusions of either diarylpropionitrile, a selective ER? agonist, or propyl-pyrazole-triol, a selective ER? agonist, attenuated Aldo/NaCl-induced hypertension in ovariectomized rats. In contrast, intracerebroventricular injections of siRNA-ER? or siRNA-ER? augmented Aldo-induced hypertension in intact females. Site-specific paraventricular nucleus (PVN) or rostroventrolateral medulla (RVLM) injections of siRNA-ER? augmented Aldo-induced hypertension. However, rats with PVN or RVLM injections of siRNA-ER? did not significantly increase blood pressure induced by Aldo. Real-time polymerase chain reaction analyses of the PVN and RVLM of siRNA-injected rat confirmed a marked reduction in the expression of ER? and ER?. In cultured PVN neurons, silencing either ER? or ER? by culturing PVN neurons with siRNA-ER? or siRNA-ER? enhanced Aldo-induced reactive oxygen species production. Ganglionic blockade after Aldo infusion showed an increase in sympathetic activity in ER? knockdown rats. These results indicate that both PVN and RVLM ER?, but not ER? in these nuclei, contribute to the protective effects of estrogen against Aldo-induced hypertension. The brain regions responsible for the protective effects of estrogen interaction with ER? in Aldo-induced hypertension still need to be determined. PMID:23608653

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

2013-04-22

286

Upregulation of osmo-mechanosensitive TRPV4 channel facilitates chronic hypoxia-induced myogenic tone and pulmonary hypertension.  

PubMed

Chronic hypoxia causes pulmonary hypertension with vascular remodeling, increase in vascular tone, and altered reactivity to agonists. These changes involve alterations in multiple Ca(2+) pathways in pulmonary arterial smooth muscle cells (PASMCs). We have previously shown that vanilloid (TRPV)- and melastatin-related transient receptor potential (TRPM) channels are expressed in pulmonary arteries (PAs). Here we found that TRPV4 was the only member of the TRPV and TRPM subfamilies upregulated in PAs of chronic hypoxic rats. The increase in TRPV4 expression occurred within 1 day of hypoxia exposure, indicative of an early hypoxic response. TRPV4 in PASMCs were found to be mechanosensitive. Osmo-mechanical stress imposed by hypotonic solution activated Ca(2+) transients; they were inhibited by TRPV4 specific short interfering RNA, the TRPV blocker ruthenium red, and the cytochrome P450 epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Consistent with TRPV4 upregulation, the Ca(2+) response induced by the TRPV4 agonist 4?-phorbol 12,13-didecanoate and hypotonicity was potentiated in hypoxic PASMCs. Moreover, a significant myogenic tone, sensitive to ruthenium red, was observed in pressurized endothelium denuded small PAs of hypoxic but not normoxic rats. The elevated basal intracellular Ca(2+) concentration in hypoxic PASMCs was also reduced by ruthenium red. In extension of these results, the development of pulmonary hypertension, right heart hypertrophy, and vascular remodeling was significantly delayed and suppressed in hypoxic trpv4(-/-) mice. These results suggest the novel concept that TRPV4 serves as a signal pathway crucial for the development of hypoxia-induced pulmonary hypertension. Its upregulation may provide a pathogenic feed-forward mechanism that promotes pulmonary hypertension via facilitated Ca(2+) influx, subsequently enhanced myogenic tone and vascular remodeling. PMID:22207590

Yang, Xiao-Ru; Lin, Amanda H Y; Hughes, Jennifer M; Flavahan, Nicholas A; Cao, Yuan-Ning; Liedtke, Wolfgang; Sham, James S K

2011-12-29

287

Upregulation of osmo-mechanosensitive TRPV4 channel facilitates chronic hypoxia-induced myogenic tone and pulmonary hypertension  

PubMed Central

Chronic hypoxia causes pulmonary hypertension with vascular remodeling, increase in vascular tone, and altered reactivity to agonists. These changes involve alterations in multiple Ca2+ pathways in pulmonary arterial smooth muscle cells (PASMCs). We have previously shown that vanilloid (TRPV)- and melastatin-related transient receptor potential (TRPM) channels are expressed in pulmonary arteries (PAs). Here we found that TRPV4 was the only member of the TRPV and TRPM subfamilies upregulated in PAs of chronic hypoxic rats. The increase in TRPV4 expression occurred within 1 day of hypoxia exposure, indicative of an early hypoxic response. TRPV4 in PASMCs were found to be mechanosensitive. Osmo-mechanical stress imposed by hypotonic solution activated Ca2+ transients; they were inhibited by TRPV4 specific short interfering RNA, the TRPV blocker ruthenium red, and the cytochrome P450 epoxygenase inhibitor N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide. Consistent with TRPV4 upregulation, the Ca2+ response induced by the TRPV4 agonist 4?-phorbol 12,13-didecanoate and hypotonicity was potentiated in hypoxic PASMCs. Moreover, a significant myogenic tone, sensitive to ruthenium red, was observed in pressurized endothelium denuded small PAs of hypoxic but not normoxic rats. The elevated basal intracellular Ca2+ concentration in hypoxic PASMCs was also reduced by ruthenium red. In extension of these results, the development of pulmonary hypertension, right heart hypertrophy, and vascular remodeling was significantly delayed and suppressed in hypoxic trpv4?/? mice. These results suggest the novel concept that TRPV4 serves as a signal pathway crucial for the development of hypoxia-induced pulmonary hypertension. Its upregulation may provide a pathogenic feed-forward mechanism that promotes pulmonary hypertension via facilitated Ca2+ influx, subsequently enhanced myogenic tone and vascular remodeling.

Yang, Xiao-Ru; Lin, Amanda H. Y.; Hughes, Jennifer M.; Flavahan, Nicholas A.; Cao, Yuan-Ning; Liedtke, Wolfgang

2012-01-01

288

Evaluation of Exercise-Induced Hypertension Post Endovascular Stenting of Coarctation of Aorta  

PubMed Central

Background: Coarctation of the aorta (COA) is a defect that accounts for 5–8% of all congenital heart diseases. Balloon angioplasty as a treatment for COA is increasingly performed, with endovascular stents having been proposed as a means of improving the efficacy and safety of the procedure. The aim of this study was to evaluate the systolic blood pressure gradient at rest and during maximal exercise at follow-up in patients post endovascular stenting of COA. Methods: Thirteen patients (4 native and 9 re-coarctation cases of COA after surgery or balloon angioplasty) with a mean age of 11.1 ± 4.7 years underwent endovascular stenting between November 2007 and December 2009 via standard techniques for native COA as an alternative to surgical repair. Doppler echocardiography was performed pre and post stenting. Resting and exercise assessment of blood pressure was performed at follow-up. Results: Post stent implantation, no angiographic major complications were evident. Systolic blood pressure gradient decreased from 42 ± 8.8 mm Hg before stent placement to 7 ± 10 mm Hg at follow-up (p value < 0.001). Peak Doppler pressure gradient decreased from 30 ± 14 mm Hg to 14 ± 10 mm Hg at follow-up (p value < 0.007). One case of exercise-induced hypertension was seen in patients. Conclusion: Endovascular stenting for native COA in older children and post-surgical COA repair in patients with residual COA and re-coarctation is a reasonable alternative to surgical correction. During early follow-up, stenting effectively alleviates the aortic arch obstruction with normalization of the systemic blood pressure both at rest and during maximal exercise.

Mortazaeian, Hojat; Moghadam, Mohammad Yoosef Aarabi; Ghaderian, Mehdi; Davary, Paridokht Nakhostin; Meraji, Mohmood; Mohammadi, Akbar Shah

2010-01-01

289

Maternal undernutrition induces differential cardiac gene expression in pulmonary hypertensive steers at high elevation.  

PubMed

Pulmonary hypertension, characterized by elevated pulmonary arterial pressure (PAP) and right ventricular hypertrophy, is caused by decreased atmospheric oxygen at high altitude. We hypothesized that maternal undernutrition programs right ventricle gene expression and sensitivity to increasing PAP at high altitude (2,183 m). On day 30 of gestation, forty Angus x Gelbvieh cows received diets to induce either gain (Control) or loss of body weight (Restricted) until day 125 of gestation. On day 126 of gestation, Restricted cows were realimented to achieve the same body weight as Controls by day 250. Parturition occurred naturally. PAP, which ranged from 40 to 114 mmHg, was determined in 15-mo-old steers from Control or Restricted cows before necropsy. At necropsy, hearts were collected from steers, separated into right and left ventricles, atria, and septa and weighed. Ventricular thickness was recorded. Eight Affymetrix bovine microarrays were screened [four high PAP (two Control and two Restricted) and four low PAP (two Control and two Restricted)] with right ventricle mRNA. This analysis revealed that pentraxin-related protein, interferon-related developmental regulator, and peroxisome proliferator-activated receptor-gamma coactivator-1alpha were differentially expressed (P < 0.05) in steer right ventricle from high-PAP cows compared with low-PAP cows. Also, activation peptide and pancreas cationic trypsinogen, alpha-actin, similar to ubiquitin carboxylesterase, were differently expressed (P < 0.05) in steers from Restricted cows compared with those from Control cows. Upregulated genes in high-PAP right ventricle have been associated with pathological cardiac hypertrophy. It is concluded that right ventricle gene expression may be differentially programmed by maternal undernutrition in the fetus during early gestation and may be detrimental to health and longevity of offspring, particularly at high altitude. PMID:18502902

Han, Hyungchul; Hansen, Thomas R; Berg, Brynn; Hess, Bret W; Ford, Stephen P

2008-05-23

290

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

PubMed Central

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.

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

291

Emblica officinalis exerts antihypertensive effect in a rat model of DOCA-salt-induced hypertension: role of (p) eNOS, NO and oxidative stress.  

PubMed

Emblica officinalis (EO) has antioxidant properties that could improve redox-sensitive vascular, cardiac and renal changes associated with deoxycorticosterone acetate/1% NaCl high salt (DOCA/HS)-induced hypertension. We determined whether hydroalcoholic lyophilized extract of EO may influence DOCA/HS-induced hypertension by modulating activity of (p) eNOS and endogenous antioxidants. Hypertension was induced in rats by DOCA-salt (20 mg/kg, s.c.) twice weekly for 5 weeks and replacing drinking water with 1% NaCl solution. These rats received cotreatment of different doses of EO (75, 150 and 300 mg/kg/day) for 5 weeks. EO significantly decreased arterial blood pressure and heart rate along with cardiac and renal hypertrophy in a dose-dependent fashion as compared to DOCA control rats. Increased TBARS and decreased endogenous antioxidants including GSH, SOD and GSHPx activity in serum, heart and kidney tissues of hypertensive rats were also normalized. Furthermore, this antihypertensive activity of EO was also linked with increased serum NO, K(+) levels and decreased Na(+) levels. Moreover, EO robustly increased activated eNOS expression in heart. Our results demonstrate that EO reduces oxidative stress, prevents development and progression of hypertension as well as cardiac and renal hypertrophy in DOCA/HS-induced hypertension via modulation of activated eNOS, endogenous antioxidants, serum NO and electrolyte levels. PMID:21748534

Bhatia, Jagriti; Tabassum, Fauzia; Sharma, Ashok Kumar; Bharti, Saurabh; Golechha, Mahaveer; Joshi, Sujata; Sayeed Akhatar, Md; Srivastava, Abhay Krishna; Arya, Dharamvir Singh

2011-09-01

292

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

PubMed Central

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.

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

293

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

PubMed

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

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

2012-10-01

294

Extracellular Superoxide Dismutase Overexpression Can Reverse the Course of Hypoxia-Induced Pulmonary Hypertension  

PubMed Central

Hypoxia leads to free radical production, which has a pivotal role in the pathophysiology of pulmonary hypertension (PH). We hypothesized that treatment with extracellular superoxide dismutase (EC-SOD) could ameliorate the development of PH induced by hypoxia. In vitro studies using pulmonary microvascular endothelial cells showed that cells transfected with EC-SOD had significantly less accumulation of xanthine oxidase and reactive oxygen species than nontransfected cells after hypoxia exposure for 24 h. To study the prophylactic role of EC-SOD, adult male wild-type (WT) and transgenic (TG) mice, with lung-specific overexpression of human EC-SOD (hEC-SOD), were exposed to fraction of inspired oxygen (FiO2) 10% for 10 d. After exposure, right ventricular systolic pressure (RVSP), right ventricular mass (RV/S + LV), pulmonary vascular wall thickness (PVWT) and pulmonary artery contraction/relaxation were assessed. TG mice were protected against PH compared with WT mice with significantly lower RVSP (23.9 ± 1.24 versus 47.2 ± 3.4), RV/S + LV (0.287 ± 0.015 versus 0.335 ± 0.022) and vascular remodeling, indicated by PVWT (14.324 ± 1.107 versus 18.885 ± 1.529). Functional studies using pulmonary arteries isolated from mice indicated that EC-SOD prevents hypoxia-mediated attenuation of nitric oxide–induced relaxation. Therapeutic potential was assessed by exposing WT mice to FiO2 10% for 10 d. Half of the group was transfected with plasmid containing cDNA encoding human EC-SOD. The remaining animals were transfected with empty vector. Both groups were exposed to FiO2 10% for a further 10 d. Transfected mice had significantly reduced RVSP (18.97 ± 1.12 versus 41.3 ± 1.5), RV/S + LV (0.293 ± 0.012 versus 0.372 ± 0.014) and PVWT (12.51 ± 0.72 versus 18.98 ± 1.24). On the basis of these findings, we concluded that overexpression of EC-SOD prevents the development of PH and ameliorates established PH.

Ahmed, Mohamed N; Zhang, Yinzhong; Codipilly, Champa; Zaghloul, Nahla; Patel, Dhara; Wolin, Michael; Miller, Edmund J

2012-01-01

295

Pulmonary arterial responses to reactive oxygen species are altered in newborn piglets with chronic hypoxia-induced pulmonary hypertension.  

PubMed

Reactive oxygen species (ROS) have been implicated in the pathogenesis of pulmonary hypertension. ROS might mediate vascular responses, at least in part, by stimulating prostanoid production. Our goals were to determine whether the effect of ROS on vascular tone is altered in resistance pulmonary arteries (PRAs) of newborn piglets with chronic hypoxia-induced pulmonary hypertension and the role, if any, of prostanoids in ROS-mediated responses. In cannulated, pressurized PRA, ROS generated by xanthine (X) plus xanthine oxidase (XO) had minimal effect on vascular tone in control piglets but caused significant vasoconstriction in hypoxic piglets. Both cyclooxygenase inhibition with indomethacin and thromboxane synthase inhibition with dazoxiben significantly blunted constriction to X+XO in hypoxic PRA. X+XO increased prostacyclin production (70 ± 8%) by a greater degree than thromboxane production (50 ± 6%) in control PRA; this was not the case in hypoxic PRA where the increases in prostacyclin and thromboxane production were not statistically different (78 ± 13% versus 216 ± 93%, respectively). Thromboxane synthase expression was increased in PRA from hypoxic piglets, whereas prostacyclin synthase expression was similar in PRA from hypoxic and control piglets. Under conditions of chronic hypoxia, altered vascular responses to ROS may contribute to pulmonary hypertension by a mechanism that involves the prostanoid vasoconstrictor, thromboxane. PMID:21516056

Fike, Candice D; Aschner, Judy L; Slaughter, James C; Kaplowitz, Mark R; Zhang, Yongmei; Pfister, Sandra L

2011-08-01

296

Pulmonary arterial responses to reactive oxygen species are altered in newborn piglets with chronic hypoxia-induced pulmonary hypertension  

PubMed Central

Reactive oxygen species (ROS) have been implicated in the pathogenesis of pulmonary hypertension. ROS might mediate vascular responses, at least in part, by stimulating prostanoid production. Our goals were to determine if the effect of ROS on vascular tone is altered in resistance pulmonary arteries (PRA) of newborn piglets with chronic hypoxia-induced pulmonary hypertension and the role, if any, of prostanoids in ROS-mediated responses. In cannulated, pressurized PRA, ROS generated by xanthine (X) plus xanthine oxidase (XO) had minimal effect on vascular tone in control piglets but caused significant vasoconstriction in hypoxic piglets. Both cyclooxygenase inhibition with indomethacin and thromboxane synthase inhibition with dazoxiben significantly blunted constriction to X+XO in hypoxic PRA. X+XO increased prostacyclin production (70±8%) by a greater degree than thromboxane production (50±6%) in control PRA; this was not the case in hypoxic PRA where the increases in prostacyclin and thromboxane production were not statistically different (78±13% versus 216±93%, respectively). Thromboxane synthase expression was increased in PRA from hypoxic piglets while prostacyclin synthase expression was similar in PRA from hypoxic and control piglets. Under conditions of chronic hypoxia, altered vascular responses to ROS may contribute to pulmonary hypertension by a mechanism that involves the prostanoid vasoconstrictor, thromboxane.

Fike, Candice D.; Aschner, Judy L.; Slaughter, James C.; Kaplowitz, Mark R.; Zhang, Yongmei; Pfister, Sandra L.

2011-01-01

297

Beneficial effects of losartan on vascular injury induced by advanced glycosylation end products and their receptors in spontaneous hypertension rats.  

PubMed

This study was designed to explore the role of losartan, an angiotensin II receptor blocker, in hypertensive injuries of blood vessels and the potential mechanisms related to the vascular advanced glycosylation end product (AGE)/receptor (RAGE) system, oxidative stress and endothelial proinflammatory factors. Spontaneously hypertensive rats (SHR) were employed for our study, and age-matched Wistar-Kyoto rats (WKY) were used for control experiments. After losartan treatment for 12 weeks, we observed by immunofluorescence that the vascular AGE level in the losartan group was significantly lower than that of the SHR group and that the vascular mRNA expression of RAGE, NF-kappaB, NADPH oxidase p47phox and ET-1, as detected by RT-PCR, was significantly lower in losartan group than in the SHR group. Meanwhile, we found that the expression of RAGE and NF-kappaB proteins in the losartan group and the WKY group was remarkably lower than that of the SHR group. Compared with the SHR group, the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) and the NO level were robustly increased, while the plasma malondialdehyde (MDA) and ET-1 were substantially reduced. These findings suggest that losartan decreases the vascular AGE level, suppresses RAGE and NF-kappaB activation, and enhances the antioxidant capacity thereby improving the endothelial function, which induce hypertensive vascular remodeling. PMID:17487457

Zhu, Wei-Wei; Liu, Xue-Ping; Wu, Nan; Zhao, Ting-Ting; Zhao, Yong; Zhang, Jie; Shao, Jian-Hua

2007-05-09

298

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

PubMed

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

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

2012-12-17

299

Maternal hypertension induces tissue-specific modulations of the apelinergic system in the fetoplacental unit in rat.  

PubMed

Apelin and its receptor APJ are expressed in fetal tissues but their function and regulation remain largely unknown. In rat, maternal treatment with a nitric oxide synthase inhibitor inducing hypertension was used to investigate apelin plasma levels in mother/fetus pairs and on the gene expression level of the apelin/APJ system in fetal tissues and placenta. At term, plasma levels of apelin were not modulated but APJ expression was increased in placenta and lung but reduced in heart. Apelin expression was increased only in the heart. We postulate that the apelinergic system may control fetal growth and cardiovascular functions in utero. PMID:22446510

Ivars, Joanna; Butruille, Laura; Knauf, Claude; Bouckenooghe, Thomas; Mayeur, Sylvain; Vieau, Didier; Valet, Philippe; Deruelle, Philippe; Lesage, Jean

2012-03-15

300

Arbutus unedo prevents cardiovascular and morphological alterations in L-NAME-induced hypertensive rats Part I: cardiovascular and renal hemodynamic effects of Arbutus unedo in L-NAME-induced hypertensive rats.  

PubMed

Hypertension induced by nitric oxide synthase inhibition is associated with functional abnormalities of the heart and kidney. The aim of the present study was to investigate whether chronic treatment with Arbutus unedo leaf (AuL) or root (AuR) aqueous extracts can prevent these alterations. Six groups of rats were used: control group received tap water; N(G)-nitro-l-arginine methyl-ester (L-NAME) group treated with L-NAME at 40 mg/kg/day; AuL and AuR groups received simultaneously L-NAME (40 mg/kg/day) and Au leaves or roots extract at the same concentration 250 mg/kg/day; l-arginine and enalapril groups received simultaneously L-NAME (40 mg/kg/day) and l-arginine at 50mg/kg/day or enalapril at 15 mg/kg/day. Treatment of rats during 4 weeks with L-NAME caused an increase of the systolic blood pressure (SBP) accompanied by a ventricular hypertrophy, an impairment of endothelium-dependent vasorelaxation, an increase of the cardiac baroreflex sensitivity and a decrease of water, sodium and potassium excretion. The co-administration of AuL or AuR extracts with L-NAME reduces the development of increased SBP, ameliorates the vascular reactivity as well as the baroreflex sensitivity and normalizes the renal function. AuR reduces the ventricular hypertrophy but AuL do not. Enalapril associated with L-NAME reverses the majority of alterations induced by L-NAME while l-arginine only lightly ameliorates the vascular reactivity. These results show that chronic treatment with Arbutus extract regress the development of hypertension and ameliorate cardiovascular and renal functions in NO deficient hypertension. PMID:18191352

Afkir, Saida; Nguelefack, Telesphore Benoit; Aziz, Mohamed; Zoheir, Johar; Cuisinaud, Guy; Bnouham, Mohamed; Mekhfi, Hassane; Legssyer, Abdelkhaleq; Lahlou, Saad; Ziyyat, Abderrahim

2007-11-26

301

Combined inhibition of 20-hydroxyeicosatetraenoic acid formation and of epoxyeicosatrienoic acids degradation attenuates hypertension and hypertension-induced end-organ damage in Ren-2 transgenic rats  

PubMed Central

Recent studies have shown that the renal cytochrome P-450 metabolites of arachidonic acid: the vasoconstrictor 20-hydroxyeicosatetraenoic acid (20-HETE), and the vasodilator epoxyeicosatrienoic acids (EETs) play an important role in the pathophysiology of angiotensin II (ANG II)-dependent forms of hypertension and the associated target organ damage. The present studies were performed in Ren-2 renin transgenic rats (TGR) to evaluate the effects of chronic selective inhibition of 20-HETE formation or elevation of the level of EETs, alone or in combination, on the course of hypertension and hypertension-associated end-organ damage. Both young (30 days of age) prehypertensive TGR and adult (190 days of age) TGR with established hypertension were examined. Normotensive Hannover Sprague-Dawley (HanSD) rats served as controls. The rats were treated with N-methylsulfonyl-12,12-dibromododec-11-enamide to inhibit 20-HETE formation and/or with N-cyclohexyl-N-dodecyl urea to inhibit soluble epoxide hydrolase and prevent degradation of EETs. Inhibition in TGR rats of 20-HETE formation combined with enhanced bioavailability of EETs attenuated the development of hypertension, cardiac hypertrophy, proteinuria, glomerular hypertrophy and sclerosis as well as renal tubulointerstitial injury. This was also associated with an attenuation of the responsiveness of the systemic and renal vascular beds to ANG II without modifying their responses to norepinephrine. Our data suggest that altered production and/or action of 20-HETE and EETs plays a permissive role in the development of hypertension and hypertension-associated end-organ damage in this model of ANG II-dependent hypertension. This information provides a basis for a search of new therapeutic approaches to the treatment of hypertension.

Certikova Chabova, Vera; Walkowska, Agnieszka; Kompanowska-Jezierska, Elzbieta; Sadowski, Janusz; Kujal, Petr; Vernerova, Zdena; Vanourkova, Zdenka; Kopkan, Libor; Kramer, Herbert J.; Falck, John R.; Imig, John D.; Hammock, Bruce D.; Vaneckova, Ivana; Cervenka, Ludek

2010-01-01

302

MODULATION OF STRESS INDUCED BY ISOMETRIC HANDGRIP TEST IN HYPERTENSIVE PATIENTS FOLLOWING YOGIC RELAXATION TRAINING  

Microsoft Academic Search

Abstract : Abstract : Abstract : Abstract : 13 essential hypertensive patients aged 41 to 60 years were given yoga training for 60 min daily, Monday through Saturday, for a total duration of 4 weeks. Blood pressure and heart rate (HR) were measured with non-invasive semi-automatic blood pressure monitor. Measurements were recorded before the training and at weekly intervals during

BHAVANANI MADANMOHAN; ASMITA PATIL; KUMAR BABU

303

Myocardial remodeling and dysfunction are induced by chronic food restriction in spontaneously hypertensive rats  

Microsoft Academic Search

Several studies have shown alterations in hearts from animals subjected to food restriction (FR). However, few experiments in hearts evaluating pressure overload have been reported. We examined the effects of chronic FR on myocardial function and morphology in spontaneously hypertensive rats (SHR). Sixty-day-old SHR were fed a control (C) or a restricted diet (daily intake reduced to 50% of amount

Marina P. Okoshi; Katashi Okoshi; Luiz S. Matsubara; Maeli Dal Pai-Silva; Ana L. Gut; Carlos R. Padovani; Vitalino Dal Pai; Antonio C. Cicogna

2006-01-01

304

Sex differences in angiotensin II- and aldosterone-induced hypertension: the central protective effects of estrogen.  

PubMed

Premenopausal women have lower blood pressure and a reduced incidence of cardiovascular disease compared with age-matched men. Similar sex differences have been seen across species and in multiple animal models of hypertension. While important progress over the last decade has been made in elucidating some of the mechanisms underlying these differences, there are still significant gaps in our knowledge. Understanding the cellular and molecular mechanisms responsible for sex differences in hypertension will be important for developing sex-specific therapies targeted toward the prevention and treatment of hypertension. Female sex hormones, especially estrogen, have been demonstrated to modulate the renin-angiotensin-aldosterone system (RAAS) and to have beneficial effects on cardiovascular function through actions not only on the kidney, heart, and vasculature, but also on the central nervous system (CNS). This review primarily focuses on the central regulatory actions of estrogen on brain nuclei involved in blood pressure regulation and the interactions between estrogen and the RAAS in the CNS by which estrogen plays an important protective role against the development of hypertension. PMID:23883676

Xue, Baojian; Johnson, Alan Kim; Hay, Meredith

2013-07-24

305

Epoprostenol-induced pulmonary vasodilatation in patients with pulmonary hypertension measured by electrical impedance tomography  

Microsoft Academic Search

Electrical impedance tomography (EIT) has been proposed as a method to monitor dynamic changes in the pulmonary vascular bed. In this study we examined the validity of EIT in the measurement of pulmonary vasodilatation in eight patients with primary and secondary pulmonary hypertension when given the vasodilating agent epoprostenol (Flolan®). Therefore, catheterization of the pulmonary artery was performed in the

H J Smit; A Vonk Noordegraaf; R J Roeleveld; J G F Bronzwaer; P E Postmus; P M J M de Vries; A Boonstra

2002-01-01

306

Sympathoexcitation by Oxidative Stress in the Brain Mediates Arterial Pressure Elevation in Obesity-Induced Hypertension  

Microsoft Academic Search

Background—Obesity is one of the major risk factors for cardiovascular disease and is often associated with increased oxidative stress and sympathoexcitation. We have already suggested that increased oxidative stress in the brain modulates the sympathetic regulation of arterial pressure in salt-sensitive hypertension, which is often associated with obesity. The present study was performed to determine whether oxidative stress could mediate

Ai Nagae; Megumi Fujita; Hiroo Kawarazaki; Hiromitsu Matsui; Katsuyuki Ando; Toshiro Fujita

2010-01-01

307

2Methoxyestradiol mediates the protective effects of estradiol in monocrotaline-induced pulmonary hypertension  

Microsoft Academic Search

When exposed to chronic hypoxia or toxin monocrotaline (MCT), female animals develop less severe pulmonary arterial hypertension (PH) compared to males; ovariectomy (OVX) exacerbates PH, and OVX animals treated with estradiol (E2) develop less severe disease. There is a line of evidence suggesting that cardiovascular protective effects of E2 are mediated by its major metabolite, 2-methoxyestradiol (2ME). Recently, we have

Stevan P. Tofovic; Xichen Zhang; Edwin K. Jackson; Sanja Dacic; Gordana Petrusevska

2006-01-01

308

Nitric Oxide Deficiency in Fenfluramine and Dexfenfluramine-induced Pulmonary Hypertension  

Microsoft Academic Search

Dexfenfluramine and fenfluramine greatly increase the risk of developing pulmonary hypertension (PHT). The mechanism of anorexigen-associated PHT (AA-PHT) and the reason PHT occurs in a mi- nority of people exposed are unknown. Anorexigens are weak pulmonary vasoconstrictors, but they become potent when synthesis of the endogenous vasodilator nitric oxide (NO) is suppressed. We hypothesized NO deficiency predisposes affected individuals to

STEPHEN L. ARCHER; KHIER DJABALLAH; MARC HUMBERT; E. KENNETH WEIR; MURIEL FARTOUKH; JOSETTE DALL' AVA-SANTUCCI; JEAN-CHRISTOPHE MERCIER; GERALD SIMONNEAU; A. TUAN DINH-XUAN

1998-01-01

309

Role of chymase in cigarette smoke-induced pulmonary artery remodeling and pulmonary hypertension in hamsters  

Microsoft Academic Search

BACKGROUND: Cigarette smoking is an important risk factor for pulmonary arterial hypertension (PAH) in chronic obstructive pulmonary disease (COPD). Chymase has been shown to function in the enzymatic production of angiotensin II (AngII) and the activation of transforming growth factor (TGF)-?1 in the cardiovascular system. The aim of this study was to determine the potential role of chymase in cigarette

Tao Wang; Su-Xia Han; Shang-Fu Zhang; Yun-Ye Ning; Lei Chen; Ya-Juan Chen; Guang-Ming He; Dan Xu; Jin An; Ting Yang; Xiao-Hong Zhang; Fu-Qiang Wen

2010-01-01

310

Anxiety-Induced Plasma Norepinephrine Augmentation Increases Reactive Oxygen Species Formation by Monocytes in Essential Hypertension  

Microsoft Academic Search

Background: An association between anxiety and depression and increased blood pressure (BP) and cardiovascular disease risk has not been firmly established. We examined the hypothesis that anxiety and depression lead to increased plasma catecholamines and to production of reactive oxygen species (ROS) by mononuclear cells (MNC) in hypertensive individuals. We also studied the role of BP in this effect.Methods: In

Kenichi Yasunari; Tokuzo Matsui; Kensaku Maeda; Munehiro Nakamura; Takanori Watanabe; Nobuo Kiriike

2006-01-01

311

Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats.  

PubMed

Excessive salt intake is known to preferentially increase blood pressure (BP) and promote kidney damage in young, salt-sensitive hypertensive human and animal models. We have suggested that mineralocorticoid receptor (MR) activation plays a major role in kidney injury in young rats. BP and urinary protein were compared in young (3-wk-old) and adult (10-wk-old) uninephrectomized (UNx) Sprague-Dawley rats fed a high (8.0%)-salt diet for 4 wk. The effects of the MR blocker eplerenone on BP and renal injury were examined in the high-salt diet-fed young UNx rats. Renal expression of renin-angiotensin-aldosterone (RAA) system components and of inflammatory and oxidative stress markers was also measured. The effects of the angiotensin receptor blocker olmesartan with or without low-dose aldosterone infusion, the aldosterone synthase inhibitor FAD286, and the antioxidant tempol were also studied. Excessive salt intake induced greater hypertension and proteinuria in young rats than in adult rats. The kidneys of young salt-loaded rats showed marked histological injury, overexpression of RAA system components, and an increase in inflammatory and oxidative stress markers. These changes were markedly ameliorated by eplerenone treatment. Olmesartan also ameliorated salt-induced renal injury but failed to do so when combined with low-dose aldosterone infusion. FAD286 and tempol also markedly reduced urinary protein. UNx rats exposed to excessive salt at a young age showed severe hypertension and renal injury, likely primarily due to MR activation and secondarily due to angiotensin receptor activation, which may be mediated by inflammation and oxidative stress. PMID:21478481

Kawarazaki, Hiroo; Ando, Katsuyuki; Fujita, Megumi; Matsui, Hiromitsu; Nagae, Ai; Muraoka, Kazuhiko; Kawarasaki, Chiaki; Fujita, Toshiro

2011-04-06

312

Obesity hypertension  

Microsoft Academic Search

The association between obesity and hypertension is well recognized. However, the exact mechanisms whereby obesity causes hypertension are complex and multifactorial. The current article summarizes some of the known mechanisms responsible for obesity hypertension.

Albert P. Rocchini

2002-01-01

313

Obesity hypertension.  

PubMed

The association between obesity and hypertension is well recognized. However, the exact mechanisms whereby obesity causes hypertension are complex and multifactorial. The current article summarizes some of the known mechanisms responsible for obesity hypertension. PMID:11866230

Rocchini, Albert P

2002-02-01

314

Tumor necrosis factor-alpha regulates inducible nitric oxide synthase gene expression in the portal hypertensive gastric mucosa of the rat.  

PubMed

Increased expression of both nitric oxide synthase (NOS) and tumor necrosis factor-alpha (TNF-alpha) have been implicated in the hyperdynamic circulation of portal hypertension. Since overexpression of these proteins would affect gastric mucosal defenses, which are impaired in portal hypertension, we examined the expression and interrelationships of TNF-alpha and NOS in the gastric mucosa of portal hypertensive rats. Following staged portal vein ligation, gastric strips from portal hypertensive rats were incubated in organ culture medium with or without TNF-alpha antibody. The expression of TNF-alpha and NOS mRNAs was assessed by reverse transcription-polymerase chain reaction (RT-PCR) at baseline and after 1, 2, and 6 hours of incubation. RT-PCR demonstrated a threefold increase in inducible NOS mRNA and a 50% increase in TNF-alpha mRNA expression at baseline in portal hypertensive animals as compared to sham-operated animals. In tissue incubated with TNF-alpha neutralizing antibody, inducible NOS mRNA expression was significantly decreased by 40%, 70%, and 80% after 1, 2, and 6 hours, respectively. Since increased TNF-alpha and NOS production could potentially impair gastric mucosal defenses, our findings suggest a major role for these proteins in the development of portal hypertensive gastropathy. PMID:9834372

Kaviani, A; Ohta, M; Itani, R; Sander, F; Tarnawski, A S; Sarfeh, I J

315

[Endocrine hypertension in pregnancy].  

PubMed

Hypertension is a frequent complication of pregnancy and may compromise fetal and maternal outcome. Hypertension may be pregnancy-induced, essential or secondary to endocrine disorders. Most cases of endocrine hypertension are the consequence of adrenal diseases. Pheochromocytoma, hypercorticism, primary aldosteronism or glucocorticoid-remediable aldosteronism can be present or diagnosed at any term and may cause severe hypertension. The most hazardous form of endocrine hypertension during pregnancy is pheochromocytoma because it may involve paroxysmal arrhythmia and/or hypertension during labor. Clinical clues and biological tests are similar to those used in non-pregnant subjects. Tests for tumor location are limited to ultrasound and magnetic resonance scans in order to avoid maternal and fetal irradiation. Medication to prepare for pheochromocytoma surgery uses alpha- and beta-blockers. The timing of surgery depends on the term of pregnancy at the diagnosis of the tumor. PMID:12442092

Launay-Mignot, P; Roueff, S; Tropeano, A-I; Thaunat, O; Plouin, P F

2002-10-01

316

Subcutaneous Administration of Sodium Alginate Oligosaccharides Prevents Salt-Induced Hypertension in Dahl Salt-Sensitive Rats.  

PubMed

Objective: We investigated the mechanism of antihypertensive effects of sodium alginate oligosaccharides, which are enzymatic products of high-molecular-weight natural alginate from seaweeds, in Dahl salt-sensitive (Dahl S) rats. Materials and Methods: Dahl S rats fed a high-salt (4% NaCl) diet were subcutaneously administered sodium alginate oligosaccharides (60 mg/day using a continuous osmotic mini-pump) for 14 days. Systolic blood pressure (SBP) was measured using the tail-cuff method, and we determined the influence of the alginate treatment on the metabolism of sodium by measuring sodium excretions in the feces and urine. Results: SBP increased in an age-dependent manner in the untreated Dahl S rats. Sodium alginate oligosaccharide treatment via the subcutaneous route almost completely abolished salt-induced hypertension in Dahl S rats fed a high-salt diet. The level of fecal or urinary sodium excretion did not significantly change during the treatment period with the alginate oligosaccharides. The reduction in SBP rapidly recovered after cessation of the treatment. Moreover, the level of urinary protein excretion was lower in the treated Dahl S rats than in the untreated rats during the experimental period. Conclusions: Our results suggest that sodium alginate oligosaccharides attenuate salt-induced hypertension in Dahl S rats not through reducing salt absorption, but probably through a direct action on vascular vessels. PMID:23484864

Moriya, Chikako; Shida, Yui; Yamane, Yuki; Miyamoto, Yuki; Kimura, Midori; Huse, Naomi; Ebisawa, Kaori; Kameda, Yuki; Nishi, Ayaka; Du, Dongdong; Yoshinaga, Mariko; Murota, Itsuki; Sato, Nobuyuki; Uehara, Yoshio

2013-03-13

317

Concealed primary aortic sarcoma induced hypertensive encephalopathy resulting from a thoracic aortic occlusion: a case report  

PubMed Central

Primary aortic sarcoma is a rare condition that is frequently associated with distal embolization. In addition, growth characteristics of primary aortic sarcoma lead to the narrowing of the involved aortic lumen. A 72-year-old Korean male with primary aortic sarcoma showed progressive unexplained blood pressure elevation that didn’t improve with additional antihypertensive drug therapy. Because follow-up measures were not taken, the patient ultimately developed hypertensive encephalopathy with concurrent embolic dissemination. Although we successfully performed open transcatheter embolectomy in both legs, the patient died because of multiple organ failure 3 days after surgery. Given the ominous prognosis for this condition, this case report highlights the fact that the value of early detection and prompt evaluation of altered vital signs should not be overemphasized. We describe a rare case of primary aortic sarcoma that showed hypertensive encephalopathy caused by thoracic aortic occlusion and also had embolic metastases to the lower extremities.

2013-01-01

318

Increased hypothalamic angiotensin-(1-7) levels in rats with aortic coarctation-induced hypertension.  

PubMed

Since angiotensin (Ang) (1-7) injected into the brain blocked Ang II pressor actions in rats made hypertensive by aortic coarctation (CH), we examined systemic and tissue angiotensin peptide levels, specifically concentrating on the hypothalamic Ang-(1-7) levels. Plasma, heart and kidney isolated from CH rats showed increased levels of Ang I, Ang II and Ang-(1-7) compared with the normotensive group, with Ang II being the predominant peptide in heart and kidney. In the hypothalamus, equimolar amounts of Ang II and Ang-(1-7) were found in the sham group, whereas only Ang-(1-7) levels increased in CH rats. We conclude that aortic coarctation activates systemic and tissue renin-angiotensin system. The increased central levels of Ang-(1-7) in the CH rats suggest a potential mitigating role of this peptide in central control of the hypertensive process. PMID:17646033

Gironacci, Mariela M; Brosnihan, K Bridget; Ferrario, Carlos M; Gorzalczany, Susana; Verrilli, María A Lopez; Pascual, Mariano; Taira, Carlos; Peña, Clara

2007-06-23

319

Modulation of oxidative stress-induced changes in hypertension and atherosclerosis by antioxidants  

PubMed Central

An imbalance between reactive oxygen species and antioxidant reserve, referred to as oxidative stress, results in the altered structure and function of proteins, lipids and DNA. Oxidative stress is associated with hypertension and atherosclerosis, but it is unknown whether it is a causative or resultant factor. The authors suggest that insulin resistance is the key element in the pathogenesis of these diseases, and leads to abnormal glucose and lipid metabolism with an increase in reactive aldehydes. These aldehydes react with the sulfhydryl and amino groups of proteins to form advanced glycation end products, adversely affecting body proteins, including antioxidant enzymes. This leads to oxidative stress. Advanced glycation end products and reactive oxygen species perpetuate a pro-oxidant state, producing the changes that are characteristic of hypertension and atherosclerosis. Antioxidants have been shown to modulate these changes. An ideal therapy for these diseases includes antioxidants, which attenuate insulin resistance, the source of oxidative stress.

Vasdev, Sudesh; Gill, Vicki D; Singal, Pawan K

2006-01-01

320

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

PubMed

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

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

2013-01-01

321

The Role of NADPH Oxidase in Chronic Intermittent Hypoxia-Induced Pulmonary Hypertension in Mice  

Microsoft Academic Search

(LV) 1 septum (S) weight ratio, an index of RV hypertrophy, and thickness of the right ventricular anterior wall as measured by echocardiography. CIH exposure also caused pulmonary vascular remodeling as demonstrated by increased muscularization of the distalpulmonaryvasculature. CIH-inducedpulmonary hypertension was associated with increased lung levels of the NADPH oxidase subunits, Nox4 and p22phox, as well as increased activity of

Rachel E. Nisbet; Anitra S. Graves; Dean J. Kleinhenz; Heidi L. Rupnow; Alana L. Reed; Tai-Hwang M. Fan; Patrick O. Mitchell; Roy L. Sutliff; C. Michael Hart

2008-01-01

322

Dietary nitrite ameliorates renal injury in l-NAME-induced hypertensive rats  

Microsoft Academic Search

Nitric oxide (NO) has numerous important functions in the kidney, and long-term blockage of nitric oxide synthases in rats by l-NAME results in severe hypertension and progressive kidney damage. On the other hand, NO production seems to be low in patients with chronic kidney disease (CKD), and NO deficiency may play a role in CKD progression.In this review, we summarized

Koichiro Tsuchiya; Shuhei Tomita; Keisuke Ishizawa; Shinji Abe; Yasumasa Ikeda; Yoshitaka Kihira; Toshiaki Tamaki

2010-01-01

323

Increased hypothalamic angiotensin-(1–7) levels in rats with aortic coarctation-induced hypertension  

Microsoft Academic Search

Since angiotensin (Ang) (1–7) injected into the brain blocked Ang II pressor actions in rats made hypertensive by aortic coarctation (CH), we examined systemic and tissue angiotensin peptide levels, specifically concentrating on the hypothalamic Ang-(1–7) levels. Plasma, heart and kidney isolated from CH rats showed increased levels of Ang I, Ang II and Ang-(1–7) compared with the normotensive group, with

Mariela M. Gironacci; K. Bridget Brosnihan; Carlos M. Ferrario; Susana Gorzalczany; María A. Lopez Verrilli; Mariano Pascual; Carlos Taira; Clara Peña

2007-01-01

324

Intratracheal Gene Transfer of Adrenomedullin Using Polyplex Nanomicelles Attenuates Monocrotaline-induced Pulmonary Hypertension in Rats  

Microsoft Academic Search

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive PAH and right ventricular failure. Despite recent advances in therapeutic approaches using prostanoids, endothelin antagonists, and so on, PAH remains a challenging condition. To develop a novel therapeutic approach, we have established a nonviral gene delivery system of poly(ethylene glycol) (PEG)-based block catiomers, which form a polyplex nanomicelle with

Mariko Harada-Shiba; Itaru Takamisawa; Kanjiro Miyata; Takehiko Ishii; Nobuhiro Nishiyama; Keiji Itaka; Kenji Kangawa; Fumiki Yoshihara; Yujiro Asada; Kinta Hatakeyama; Noriya Nagaya; Kazunori Kataoka

2009-01-01

325

Simvastatin and Losartan Enhance Nitric Oxide and Reduce Oxidative Stress in Salt-Induced Hypertension  

Microsoft Academic Search

Background: The renin-angiotensin-aldosterone system and oxidative stress play a major role in the pathogenesis of hypertension.Methods: We examined the effects of simvastatin, an HMG-CoA inhibitor, and losartan, an angiotensin type 1 receptor antagonist, in Dahl rats fed a high salt diet (8% NaCl), and treated with either simvastatin (3 mg\\/kg\\/d), losartan (10 mg\\/kg\\/d), or their combination using the drinking water

Mohamed A. Bayorh; Agaba A. Ganafa; Danita Eatman; Marcus Walton; Giora Z. Feuerstein

2005-01-01

326

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

PubMed Central

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.

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

2013-01-01

327

Automated measurement of sFlt1, PlGF and sFlt1/PlGF ratio in differential diagnosis of hypertensive pregnancy disorders.  

PubMed

Objectives: The utility of angiogenic and antiangiogenic biomarkers as diagnostic tools in preeclampsia (PE) has been shown in previous studies. Our study's aim was to evaluate the use of automated measurement of sFlt1, PlGF and their ratio (sFlt1/PlGF) in differential diagnosis of hypertensive pregnancy disorders. Patients/Methods: Sixty-four patients with PE/HELLP, 18 with pregnancy-induced hypertension (PIH), 22 with gestational proteinuria (GP) and 232 controls were investigated. The PE/HELLP group was divided into mild PE (mPE, n?=?31), severe PE (sevPE, n?=?20), superimposed PE (supPE, n?=?7) and HELLP syndrome (n?=?6). sFlt1 and PlGF were measured in serum samples on an automated platform. Statistical analysis was performed using parametric and non-parametric methods, ROC analysis and logistic regression method. Results: PE patients showed higher sFlt1 and ratio and lower PlGF than controls (median?±?SEM in pg/mL; 10?888?±?878 versus 2456?±?116; 268?±?39 versus 16?±?2 and 68?±?6 versus 439?±?37, each p?PIH and GP showed significant differences compared to controls (p???0.01, respectively), mPE (p???0.007), sevPE (p?hypertensive pregnancy disorders and gives additional valuable information for clinical management. PMID:23957293

Engels, Theresa; Pape, Juliane; Schoofs, Katharina; Henrich, Wolfgang; Verlohren, Stefan

2013-08-19

328

NADPH oxidases and reactive oxygen species at different stages of chronic hypoxia-induced pulmonary hypertension in newborn piglets.  

PubMed

Recently, we reported that reactive oxygen species (ROS) generated by NADPH oxidase (NOX) contribute to aberrant responses in pulmonary resistance arteries (PRAs) of piglets exposed to 3 days of hypoxia (Am J Physiol Lung Cell Mol Physiol 295: L881-L888, 2008). An objective of the present study was to determine whether NOX-derived ROS also contribute to altered PRA responses at a more advanced stage of pulmonary hypertension, after 10 days of hypoxia. We further wished to advance knowledge about the specific NOX and antioxidant enzymes that are altered at early and later stages of pulmonary hypertension. Piglets were raised in room air (control) or hypoxia for 3 or 10 days. Using a cannulated artery technique, we found that treatments with agents that inhibit NOX (apocynin) or remove ROS [an SOD mimetic (M40403) + polyethylene glycol-catalase] diminished responses to ACh in PRAs from piglets exposed to 10 days of hypoxia. Western blot analysis showed an increase in expression of NOX1 and the membrane fraction of p67phox. Expression of NOX4, SOD2, and catalase were unchanged, whereas expression of SOD1 was reduced, in arteries from piglets raised in hypoxia for 3 or 10 days. Markers of oxidant stress, F(2)-isoprostanes, measured by gas chromatography-mass spectrometry, were increased in PRAs from piglets raised in hypoxia for 3 days, but not 10 days. We conclude that ROS derived from some, but not all, NOX family members, as well as alterations in the antioxidant enzyme SOD1, contribute to aberrant PRA responses at an early and a more progressive stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets. PMID:19592458

Dennis, Kathleen E; Aschner, J L; Milatovic, D; Schmidt, J W; Aschner, M; Kaplowitz, M R; Zhang, Y; Fike, Candice D

2009-07-10

329

Effect of A-HRS on blood pressure and metabolic alterations in fructose-induced hypertensive rats.  

PubMed

Fructose feeding induces a rise in blood pressure in normal rats that is associated with insulin resistance, hyperinsulinemia, hyperglycaemia, hypercholesterolaemia and hypertriglyceridaemia. We have examined the effect of chronic administration of A-HRS (100 and 300?mg?kg?¹; p.o.) isolated from Hibiscus rosa sinensis (Malvaceae) on systolic blood pressure (SBP), vascular reactivity, serum glucose, triglycerides, cholesterol, uric acid and insulin in fructose-induced hypertension model. A-HRS treatment (100 and 300?mg?kg?¹, p.o. for 6 weeks) reduced SBP, vascular reactivity changes to catecholamines and reversed the metabolic alterations induced by fructose (10%) treatment for 6 weeks. The cumulative concentration response curve (CCRC) of angiotensin II (Ang II) was shifted towards the right in rats treated with A-HRS using an isolated strip of ascending colon. The results suggest that A-HRS could prevent the development of high-blood pressure induced by a diet rich in fructose, probably by reversing the metabolic alterations induced by fructose. In conclusion, A-HRS has an antihypertensive action in a fructose model. PMID:21790490

Mohan, Mahalaxmi; Khade, Bhagyashree; Shinde, Amol

2011-07-27

330

Effects of 9 Kampo medicines clinically used in hypertension on hemodynamic changes induced by theophylline in rats.  

PubMed

We examined the effects of 9 kinds of Kampo medicines, which are clinically used for the treatment of hypertension, on anesthetized rats with increases in arterial blood pressure, heart rate and peripheral blood flow induced by theophylline (5 mg/kg, i.v.) that were partially or completely mediated by endogenous catecholamines. Each Kampo medicine (1 g/kg) was intraduodenaly administered. Shinbu-to caused a severe disturbance of the arterial blood pressure. Saiko-ka-ryukotsu-borei-to, Oren-gedoku-to, San'o-shashin-to and Dai-jyoki-to had hypotensive effects, while Hachimi-jio-gan, Gosha-jinki-gan, Dai-saiko-to and Choto-san did not have such an effect. Moreover, Saiko-ka-ryukotsu-borei-to attenuated the heart rate. In Oren-gedoku-to, San'o-shashin-to and Dai-jyoki-to, a reduction in peripheral blood flow was observed. These results suggest that Saiko-ka-ryukotsuborei-to, Oren-gedoku-to, San'o-shashin-to and Dai-jyoki-to are ameliorative to the hypertension in sympathetic system dominance and Shinbu-to is occasionally dangerous to it. PMID:10864032

Sanae, F; Komatsu, Y; Amagaya, S; Chisaki, K; Hayashi, H

2000-06-01

331

Two-hour insulinemia after oral glucose overload and women at risk of pregnancy-induced hypertensive disorders.  

PubMed

Objective: Pregnant women with impaired insulin sensitivity are at risk for developing pregnancy-induced hypertensive disorders (PIHD). We analyzed glucose and insulin circulating levels throughout a 2-h oral 75?g glucose tolerance test in pregnant women, and related the 2-h insulinemias to PIHD prevalence. Methods: Pregnant women (gestational week 24-28) were submitted to a glucose overload, and glucose and insulin plasma concentrations were measured throughout the test. These peripheral metabolite levels, the homeostasis model assessment (HOMA) values and the glucose to insulin ratio (G:Ir) were analyzed. Anthropometric parameters and pregnancy outcome were recorded. Results: Women with normal fasting glycemia, insulinemia and HOMA values, G:Ir and 2?h-glycemia but whose 2?h-insulinemia was higher than 215.25?pM were at greater risk for developing late pregnancy hypertension and preeclampsia compared to women of similar characteristics but whose 2?h-insulinemias were lower than 215.25?pM. Conclusion: 2-h insulinemias higher than 215.25?pM after a 75?g glucose overload could be highly indicative of women at increased risk of developing PIHD. PMID:23844648

Romero, José; Spinedi, Eduardo

2013-07-11

332

5-Hydroxytryptamine levels in the pulmonary arterioles of broilers with induced pulmonary hypertension and its relationship to pulmonary vascular remodelling.  

PubMed

This experiment was performed to explore the relationship between 5-hydroxytryptamine (5-HT) levels in pulmonary arterioles and in pulmonary vascular remodelling in broilers. Pulmonary arterial hypertension was induced by injecting cellulose microparticles intravenously. Pulmonary hypertension syndrome (PHS) morbidity, right ventricle/total ventricle weight ratio (RV/TV), packed cell volume (PCV), haemoglobin concentration (HB), vessel wall area to vessel total area ratio (WA/TA) and mean tunica media thickness in pulmonary arterioles (mMTPA) were measured. Proliferating cell nuclear antigen (PCNA), argyrophilic nucleolar organizer region proteins (Ag-NORs) and 5-HT content in pulmonary arterioles were determined. The results showed that injecting cellulose microparticles intravenously in broilers could successfully increase the PHS morbidity, significantly elevate RV/TV, PCV and HB, significantly increase mMTPA and WA/TA, and significantly increase the argyrophilic particles in smooth muscle cell nucleoli, PCNA-positive cells in the medial layer, and the 5-HT content in pulmonary arterioles. Correlation analysis showed that the level of 5-HT was strongly positively correlated with PCNA and Ag-NORs. The results indicated that the increase of 5-HT in the tunica media could possibly promote the proliferation of smooth muscle cells in pulmonary arterioles and thus the occurrence of pulmonary vascular remodelling. PMID:23782167

Li, Ying; Zeng, Jian-Ying; Tang, Zhao-Xin; Li, Yu-Gu; Guo, Jian-Ying; Pan, Jia-Qiang

2013-06-19

333

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

PubMed Central

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.

2013-01-01

334

PVN adenovirus-siRNA injections silencing either NOX2 or NOX4 attenuate aldosterone/NaCl-induced hypertension in mice.  

PubMed

Mineralocorticoid excess increases superoxide production by activating NADPH oxidase (NOX), and intracerebroventricular infusions of NADPH oxidase inhibitors attenuate aldosterone (Aldo)/salt-induced hypertension. It has been hypothesized that increased reactive oxygen species (ROS) in the brain may be a key mechanism in the development of hypertension. The present study investigated the brain regional specificity of NADPH oxidase and the role of NOX2 and NOX4 NADPH oxidase subunits in the hypothalamic paraventricular nucleus (PVN) in Aldo/salt-induced hypertension. PVN injections of adenoviral vectors expressing small interfering (si)RNA targeting NOX2 (AdsiRNA-NOX2) or NOX4 (AdsiRNA-NOX4) mRNAs were used to knock down NOX2 and NOX4 proteins. Three days later, delivery of Aldo (0.2 mg·kg(-1)·day(-1) sc) via osmotic pump commenced and 1% NaCl was provided in place of water. PVN injections of either AdsiRNA-NOX2 or AdsiRNA-NOX4 significantly attenuated the development of Aldo/NaCl-induced hypertension. In an additional study, Aldo/salt-induced hypertension was also significantly attenuated in NOX2 (genomic) knockout mice compared with wild-type controls. When animals from both functional studies underwent ganglionic blockade, there was a reduced fall in blood pressure in the NOX2 and NOX4 knockdown/knockout mice. Western blot analyses of the PVN of siRNA-NOX2- or siRNA-NOX4-injected mice confirmed a marked reduction in the expression of NOX2 or NOX4 protein. In cultured PVN neurons, silencing either NOX2 or NOX4 protein production by culturing PVN cells with siRNA-NOX2 or siRNA-NOX4 attenuated Aldo-induced ROS. These data indicate that both NOX2 and NOX4 in the PVN contribute to elevated sympathetic activity and the hypertensivogenic actions induced by mineralocorticoid excess. PMID:22140041

Xue, Baojian; Beltz, Terry G; Johnson, Ralph F; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

2011-12-02

335

Uridine adenosine tetraphosphate-induced contraction is increased in renal but not pulmonary arteries from DOCA-salt hypertensive rats.  

PubMed

Uridine adenosine tetraphosphate (Up(4)A) was reported as a novel endothelium-derived contracting factor. Up(4)A contains both purine and pyrimidine moieties, which activate purinergic (P2)X and P2Y receptors. However, alterations in the vasoconstrictor responses to Up(4)A in hypertensive states remain unclear. The present study examined the effects of Up(4)A on contraction of isolated renal arteries (RA) and pulmonary arteries (PA) from DOCA-salt rats using isometric tension recording. RA from DOCA-salt rats exhibited increased contraction to Up(4)A versus arteries from control uninephrectomized rats in the absence and presence of N(G)-nitro-l-arginine (nitric oxide synthase inhibitor). On the other hand, the Up(4)A-induced contraction in PA was similar between the two groups. Up(4)A-induced contraction was inhibited by suramin (nonselective P2 antagonist) but not by diinosine pentaphosphate pentasodium salt hydrate (Ip(5)I; P2X(1) antagonist) in RA from both groups. Furthermore, 2-thiouridine 5'-triphosphate tetrasodium salt (2-ThioUTP; P2Y(2) agonist)-, uridine-5'-(?-thio)-triphosphate trisodium salt (UTP?S; P2Y(2)/P2Y(4) agonist)-, and 5-iodouridine-5'-O-diphosphate trisodium salt (MRS 2693; P2Y(6) agonist)-induced contractions were all increased in RA from DOCA-salt rats. Protein expression of P2Y(2)-, P2Y(4)-, and P2Y(6) receptors in RA was similar between the two groups. In DOCA-salt RA, the enhanced Up(4)A-induced contraction was reduced by PD98059, an ERK pathway inhibitor, and Up(4)A-stimulated ERK activation was increased. These data are the first to indicate that Up(4)A-induced contraction is enhanced in RA from DOCA-salt rats. Enhanced P2Y receptor signaling and activation of the ERK pathway together represent a likely mechanism mediating the enhanced Up(4)A-induced contraction. Up(4)A might be of relevance in the pathophysiology of vascular tone regulation and renal dysfunction in arterial hypertension. PMID:21551273

Matsumoto, Takayuki; Tostes, Rita C; Webb, R Clinton

2011-05-06

336

Cytochrome P4501A1 is Required for Vascular Dysfunction and Hypertension Induced by 2,3,7,8-Tetrachlorodibenzo-p-dioxin  

Technology Transfer Automated Retrieval System (TEKTRAN)

National Health and Nutrition Examination Survey data show an association between hypertension and exposure to dioxin-like halogenated aromatic hydrocarbons (HAH). Further, chronic exposure of mice to the prototypical HAH, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), induces reactive oxygen species (...

337

Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats  

Microsoft Academic Search

Acetylsalicylic acid (aspirin), used to reduce risk of cardiovascular disease, plays an important role in the regulation of cellular proliferation. However, mechanisms responsible for aspirin-induced growth inhibition are not fully understood. Here, we investigated whether aspirin may exert therapeutic effects via AMP-activated protein kinase (AMPK) activation in vascular smooth muscle cells (VSMC) from wistar kyoto rats (WKY) and spontaneously hypertensive

Jin Young Sung; Hyoung Chul Choi

2011-01-01

338

Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats.  

PubMed

In Dahl salt-sensitive (S) rats, high salt intake increases cerebrospinal fluid (CSF) Na(+) concentration ([Na(+)]) and blood pressure (BP). Intracerebroventricular (ICV) infusion of a mineralocorticoid receptor (MR) blocker prevents the hypertension. To assess the role of aldosterone locally produced in the brain, we evaluated the effects of chronic central blockade with the aldosterone synthase inhibitor FAD286 and the MR blocker spironolactone on changes in aldosterone and corticosterone content in the hypothalamus and the increase in CSF [Na(+)] and hypertension induced by high salt intake in Dahl S rats. After 4 wk of high salt intake, plasma aldosterone and corticosterone were not changed, but hypothalamic aldosterone increased by approximately 35% and corticosterone tended to increase in Dahl S rats, whereas both steroids decreased by approximately 65% in Dahl salt-resistant rats. In Dahl S rats fed the high-salt diet, ICV infusion of FAD286 or spironolactone did not affect the increase in CSF [Na(+)]. ICV infusion of FAD286 prevented the increase in hypothalamic aldosterone and 30 mmHg of the 50-mmHg BP increase induced by high salt intake. ICV infusion of spironolactone fully prevented the salt-induced hypertension. These results suggest that, in Dahl S rats, high salt intake increases aldosterone synthesis in the hypothalamus and aldosterone acts as the main MR agonist activating central pathways contributing to salt-induced hypertension. PMID:19118098

Huang, Bing S; White, Roselyn A; Jeng, Arco Y; Leenen, Frans H H

2008-12-31

339

The effect of nifedipine alone or combined with low dose acetylsalicylic acid on endotoxin-induced pulmonary hypertension in the piglet  

Microsoft Academic Search

Cardiovascular responses to the calcium antagonist nifedipine, alone and combined with low dose acetylsalicylic acid (ASA), were evaluated in a piglet model of endotoxin-induced pulmonary hypertension. All animals were anesthetized, paralyzed and mechanically ventilated. Cardiac output (CO), pulmonary artery pressure (PAP), aortic blood pressure (SAP), pulmonary capillary wedge pressure (PCWP), right strial pressure (RAPM) and arterial blood gases were measured

D. Schranz; R. G. Huth; H. Stopfkuchen; B.-K. Jüngst

1988-01-01

340

Abrogated Leptin-Induced Cardiac Contractile Response in Ventricular Myocytes Under Spontaneous Hypertension Role of JAK\\/STAT Pathway  

Microsoft Academic Search

Leptin regulates cardiovascular function. Leptin levels are elevated in obesity and hypertension and may play a role in cardiovascular dysfunctions in these comorbidities. This study was designed to determine the influence of hypertension on the cardiac contractile response of leptin. Mechanical and intracellular Ca 2 properties were evaluated using an IonOptix system in ventricular myocytes from spontaneously hypertensive (SHR) and

Loren E. Wold; David P. Relling; Jinhong Duan; Faye L. Norby; Jun Ren

341

Dexmedetomidine Use in the Setting of Cocaine-Induced Hypertensive Emergency and Aortic Dissection: A Novel Indication  

PubMed Central

Aortic dissection is a potentially fatal but rare disease characterized by an aortic intimal tear with blood passing into the media creating a false lumen and with resultant high mortality depending on the location of dissection if not aggressively treated. Cocaine users are known to have a higher incidence of aortic dissection. We report here aortic dissection in a patient with cocaine abuse which did not respond to traditional medication regimes used currently in this setting. Worth mentioning is the use of an alpha-2 receptor selective agonist named Dexmedetomidine as a treatment modality to control hypertension in this patient, which is approved only for sedation of intubated and mechanically ventilated patients in the intensive care settings and for sedation during invasive procedures. This paper illustrates the practical beneficial role of Dexmedetomidine in controling blood pressure in the settings of cocaine-induced sympathetic surge when other treatment modalities fail.

Javed, Fahad; Benjo, Alexandre Miguel; Reddy, Kiran; Shoaib Akram, Muhammad; Khan, Shahzeb Afsar; Sabharwal, Manpreet Singh; Nadkarni, Girish; Aziz, Emad F.; Herzog, Eyal

2011-01-01

342

Endothelin but Not Angiotensin II May Mediate Hypertension-Induced Coronary Vascular Calcification in Chronic Kidney Disease  

PubMed Central

To understand the relationship between putative neurohormonal factors operative in hypertension and coronary artery calcification (CAC), the relevant cellular actions of angiotensin (Ang II) and endothelin-1 (ET-1) are reviewed. There is compelling evidence to implicate ET-1 in CAC. ET-1 increases phosphate transport with a 42 to 73% increase in Vmax. Increased cellular phosphate may induce CAC through increased Ca x phosphate product, transformation of vascular smooth muscle cells into a bone-producing phenotype or cell apoptosis that releases procalcific substances. ET-1 is increased in several models of vascular calcification. ET-1 inhibits inhibitors of calcification, matrix Gla and osteoprotegerin, while enhancing pro-calcific factors such as BMP-2 and osteopontin. In contrast, Ang II inhibits phosphate transport decreasing Vmax by 38% and increases matrix Gla. Ang II also stimulates bone resorption. Vascular calcification is reduced by ET-1 A receptor antagonists and to a greater extent than angiotensin receptor blockade although both agents reduce blood pressure.

Rabkin, Simon W.

2011-01-01

343

Effect of a Phosphodiesterase 5 Inhibitor on Pulmonary and Cerebral Arteries of Newborn Piglets with Chronic Hypoxia-Induced Pulmonary Hypertension  

PubMed Central

Background The use of phosphodiesterase 5 (PDE5) inhibitors to treat newborns with pulmonary hypertension is increasing. The effect of PDE5 inhibitors on the neonatal cerebral circulation remains unknown. The neonatal piglet model of chronic hypoxia-induced pulmonary hypertension allows the study of the effects of PDE5 inhibitors on both the pulmonary and cerebral circulations. Objectives: To determine whether the PDE5 inhibitor, zaprinast, causes dilation in pulmonary and middle cerebral arteries (MCA) of normoxic newborn piglets and those with chronic hypoxia-induced pulmonary hypertension, and to evaluate whether zaprinast alters responses to increased pressure (autoregulatory ability) of the MCA. Methods Two-day-old piglets were raised in normoxia or hypoxia for 3 or 10 days. Pulmonary arteries and MCA were isolated and pressurized, after which changes in diameter to zaprinast were measured. MCA pressure-diameter relationships were determined. Results Dilation to zaprinast was similar in pulmonary arteries from normoxic and hypoxic piglets. Zaprinast dilated MCA from all groups but the response was diminished in MCA from piglets raised in hypoxia for 10 days. MCA pressure-diameter relationships (autoregulation) did not differ between the groups. Conclusions Pulmonary artery dilation to zaprinast supports the use of PDE5 inhibitors to treat pulmonary hypertension in neonates. PDE5 inhibitors function as MCA dilators but do not impair the pressure-diameter behavior of the cerebral circulation of either normoxic newborn piglets or those with chronic hypoxia-induced pulmonary hypertension. These findings suggest that cerebral autoregulation is likely to be intact with acute PDE5 inhibitor treatment in infants with pulmonary hypertension in conditions associated with chronic hypoxia.

Fike, Candice D.; Kaplowitz, Mark; Zhang, Yongmei; Dantuma, Mark; Madden, Jane A.

2011-01-01

344

Protein complex formation with heat shock protein 90 in chronic hypoxia-induced pulmonary hypertension in newborn piglets.  

PubMed

Aberrant interactions between heat shock protein (Hsp)90 and its client proteins could contribute to pulmonary hypertension. We tested the hypotheses that 1) the interaction between Hsp90 and its known client protein, endothelial nitric oxide synthase (eNOS), is impaired in pulmonary resistance arteries (PRAs) from piglets with pulmonary hypertension caused by exposure to 3 or 10 days of hypoxia and 2) Hsp90 interacts with the prostanoid pathway proteins prostacyclin synthase (PGIS) and/or thromboxane synthase (TXAS). We also determined whether Hsp90 antagonism with geldanamycin alters the agonist-induced synthesis of prostacyclin and thromboxane or alters PRA responses to these prostaglandin metabolites. Compared with normoxic piglets, less eNOS coimmunoprecipitated with Hsp90 in PRAs from hypoxic piglets. Despite reduced Hsp90-eNOS interactions, dilation to ACh was enhanced in geldanamycin-treated PRAs from hypoxic, but not normoxic, piglets. In PRAs from all groups of piglets, PGIS and TXAS coimmunoprecipitated with Hsp90. Geldanamycin reduced the ACh-induced synthesis of prostacyclin and thromboxane and altered responses to the thromboxane mimetic U-46619 in PRAs from all groups. Although geldanamycin enhanced responses to prostacyclin in PRAs from both groups of hypoxic piglets, geldanamycin had no effect on prostacyclin responses in PRAs from either group of normoxic piglets. Our findings indicate that Hsp90 influences both prostanoid and eNOS signaling in the pulmonary circulation of newborn piglets and that the impact of pharmacological inhibition of Hsp90 on these signaling pathways is altered during exposure to chronic hypoxia. PMID:20693398

Fike, Candice D; Pfister, Sandra L; Slaughter, James C; Kaplowitz, Mark R; Zhang, Yongmei; Zeng, Heng; Frye, Naila Rashida; Aschner, Judy L

2010-08-06

345

Vascular reactivity to calcitonin gene-related peptide is enhanced in subtotal nephrectomy-salt induced hypertension.  

PubMed

In subtotal nephrectomy (SN)- and salt-induced hypertension, calcitonin gene-related peptide (CGRP) plays a compensatory role to attenuate the blood pressure increase in the absence of an increase in the neuronal synthesis and release of this peptide. Therefore, the purpose of this study was to determine whether the mechanism of this antihypertensive activity is through enhanced sensitivity of the vasculature to the dilator actions of this neuropeptide. Hypertension was induced in Sprague-Dawley rats by SN and 1% saline drinking water. Control rats were sham-operated and given tap water to drink. After 11 days, rats had intravenous (drug administration) and arterial (continuous mean arterial pressure recording) catheters surgically placed and were studied in a conscious unrestrained state. Baseline mean arterial pressure was higher in the SN-salt rats (157 ± 5 mmHg) compared with controls (128 ± 3 mmHg). Administration of CGRP (and adrenomedullin) produced a significantly greater dose-dependent decrease in mean arterial pressure in SN-salt rats compared with controls (?2.0-fold for both the low and high doses). Interestingly, isolated superior mesenteric arterioles from SN-salt rats were significantly more responsive to the dilator effects of CGRP (but not adenomedullin) than the controls (pEC(50), SN-salt, 14.0 ± 0.1 vs. control, 12.0 ± 0.1). Analysis of the CGRP receptor proteins showed that only the receptor component protein was increased significantly in arterioles from SN-salt rats. These data indicate that the compensatory antihypertensive effects of CGRP result from an increased sensitivity of the vasculature to dilator activity of this peptide. The mechanism may be via the upregulation of receptor component protein, thereby providing a more efficient coupling of the receptor to the signal transduction pathways. PMID:21666123

Supowit, Scott C; Katki, Khurshed A; Hein, Travis W; Gupta, Prakash; Kuo, Lih; Dickerson, Ian M; Dipette, Donald J

2011-06-10

346

Vascular reactivity to calcitonin gene-related peptide is enhanced in subtotal nephrectomy-salt induced hypertension  

PubMed Central

In subtotal nephrectomy (SN)- and salt-induced hypertension, calcitonin gene-related peptide (CGRP) plays a compensatory role to attenuate the blood pressure increase in the absence of an increase in the neuronal synthesis and release of this peptide. Therefore, the purpose of this study was to determine whether the mechanism of this antihypertensive activity is through enhanced sensitivity of the vasculature to the dilator actions of this neuropeptide. Hypertension was induced in Sprague-Dawley rats by SN and 1% saline drinking water. Control rats were sham-operated and given tap water to drink. After 11 days, rats had intravenous (drug administration) and arterial (continuous mean arterial pressure recording) catheters surgically placed and were studied in a conscious unrestrained state. Baseline mean arterial pressure was higher in the SN-salt rats (157 ± 5 mmHg) compared with controls (128 ± 3 mmHg). Administration of CGRP (and adrenomedullin) produced a significantly greater dose-dependent decrease in mean arterial pressure in SN-salt rats compared with controls (?2.0-fold for both the low and high doses). Interestingly, isolated superior mesenteric arterioles from SN-salt rats were significantly more responsive to the dilator effects of CGRP (but not adenomedullin) than the controls (pEC50, SN-salt, 14.0 ± 0.1 vs. control, 12.0 ± 0.1). Analysis of the CGRP receptor proteins showed that only the receptor component protein was increased significantly in arterioles from SN-salt rats. These data indicate that the compensatory antihypertensive effects of CGRP result from an increased sensitivity of the vasculature to dilator activity of this peptide. The mechanism may be via the upregulation of receptor component protein, thereby providing a more efficient coupling of the receptor to the signal transduction pathways.

Katki, Khurshed A.; Hein, Travis W.; Gupta, Prakash; Kuo, Lih; Dickerson, Ian M.; DiPette, Donald J.

2011-01-01

347

Exercise induced renal dysfunction demonstrated both in hypertensives and normotensive controls studies by Tc-99m-DTPA  

SciTech Connect

It was previously reported that the hippurate transport disturbance after exercise is a specific phenomenon to patients with hypertension. The authors' study with Tc-99m-DTPA revealed exercise induced renal dysfunction not only in hypertensives (H) but also in normotensive controls (N). The details of the investigation is presented. Tc-99m-DTPA was intravenously injected at rest and during bicycle ergometric stress to 14 H and 14 N in sitting position. Serial dynamic renal images were taken, of which data were simultaneously stored in a data processor for later analysis. The renogram was drawn setting ROI on each kidney. Peak counts (PC) of vascular phase, peak time (PT) of secretory phase and radioisotope retention rate (RR) at 10 minutes were the parameters being compared between at rest and at exercise. GFR of each kidney was determined. Blood samples were obtained at rest and at the end of exercise for the measurement of aldosterone (ALD), plasma renin activity (PRA) and catecholamines (A, NA). Exercise caused significant lowering of PC, prolongation of PT and increase in RR (10 min. counts/peak counts) both in H and N. GFR (miota/min.) during exercise was significantly lower than at rest in both H (80 +- 22 vs 93.8 +- 16.9, p<0.02) and N (84 +- 17 vs 102 +- 15, p<0.01). ALD, PRA, A and NA are all elevated during exercise both in H and N. None of the rest-exercise differences significantly differed between H and N. The data indicate the exercise induced renal dysfunction demonstrated by Tc-99m-DTPA renograms is not specified to H but can also be observed in N, which may be resulted from the common changes in H and N of GFR and humoral factors.

Mizuiri, S.; Hayashi, I.; Ohara, T.; Hirata, K.; Sasaki, Y.

1985-05-01

348

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

PubMed

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

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

2010-03-03

349

Cimicifuga racemosa impairs fatty acid ?-oxidation and induces oxidative stress in livers of ovariectomized rats with renovascular hypertension.  

PubMed

The aim of this work was to evaluate the effects of therapeutic doses of Cimicifuga racemosa on cardiovascular parameters and on liver lipid metabolism and redox status in an animal model of estrogen deficiency associated with hypertension, a condition that could make the liver more vulnerable to drug-induced injuries. Female Wistar rats were subjected to the surgical procedures of bilateral ovariectomy (OVX) and induction of renovascular hypertension (two-kidneys, one-clip; 2K1C). These animals (OVX + 2K1C) were treated with daily doses of a C. racemosa extract, using a dose that is similar to that recommended to postmenopausal women (0.6 mg/kg), over a period of 15 days. The results were compared to those of untreated OVX + 2K1C, OVX, and control rats. The treatment with C. racemosa caused a significant reduction in blood pressure. In the liver, treatment did not prevent the development of steatosis, and it reduced the mitochondrial and peroxisomal capacity to oxidize octanoyl-CoA compared to the untreated animals. In addition, C. racemosa caused numerous undesirable effects on the liver redox status: it increased the mitochondrial reactive oxygen species generation, an event that was not accompanied by an increase in the activity of superoxide dismutase, and it induced a decrease in peroxisomal catalase activity. Although the reduced glutathione content had not been affected, a phenomenon that probably reflected the restoration of glucose-6-phosphate dehydrogenase activity by C. racemosa, oxidative damage was evidenced by the elevated level of thiobarbituric acid-reactive substances found in the liver of treated animals. PMID:22684021

Campos, Lilian Brites; Gilglioni, Eduardo Hideo; Garcia, Rosângela Fernandes; Brito, Márcia do Nascimento; Natali, Maria Raquel Marçal; Ishii-Iwamoto, Emy Luiza; Salgueiro-Pagadigorria, Clairce Luzia

2012-06-07

350

CTGF disrupts alveolarization and induces pulmonary hypertension in neonatal mice: implication in the pathogenesis of severe bronchopulmonary dysplasia  

PubMed Central

The pathological hallmarks of bronchopulmonary dysplasia (BPD), one of the most common long-term pulmonary complications associated with preterm birth, include arrested alveolarization, abnormal vascular growth, and variable interstitial fibrosis. Severe BPD is often complicated by pulmonary hypertension characterized by excessive pulmonary vascular remodeling and right ventricular hypertrophy that significantly contributes to the mortality and morbidity of these infants. Connective tissue growth factor (CTGF) is a multifunctional protein that coordinates complex biological processes during tissue development and remodeling. We have previously shown that conditional overexpression of CTGF in airway epithelium under the control of the Clara cell secretory protein promoter results in BPD-like architecture in neonatal mice. In this study, we have generated a doxycycline-inducible double transgenic mouse model with overexpression of CTGF in alveolar type II epithelial (AT II) cells under the control of the surfactant protein C promoter. Overexpression of CTGF in neonatal mice caused dramatic macrophage and neutrophil infiltration in alveolar air spaces and perivascular regions. Overexpression of CTGF also significantly decreased alveolarization and vascular development. Furthermore, overexpression of CTGF induced pulmonary vascular remodeling and pulmonary hypertension. Most importantly, we have also demonstrated that these pathological changes are associated with activation of integrin-linked kinase (ILK)/glucose synthesis kinase-3? (GSK-3?)/?-catenin signaling. These data indicate that overexpression of CTGF in AT II cells results in lung pathology similar to those observed in infants with severe BPD and that ILK/GSK-3?/?-catenin signaling may play an important role in the pathogenesis of severe BPD.

Chen, Shaoyi; Rong, Min; Platteau, Astrid; Hehre, Dorothy; Smith, Heather; Ruiz, Philip; Whitsett, Jeffrey; Bancalari, Eduardo

2011-01-01

351

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

PubMed Central

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.

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

2009-01-01

352

Losartan attenuates chronic cigarette smoke exposure-induced pulmonary arterial hypertension in rats: Possible involvement of angiotensin-converting enzyme-2  

Microsoft Academic Search

Chronic cigarette smoking induces pulmonary arterial hypertension (PAH) by largely unknown mechanisms. Renin–angiotensin system (RAS) is known to function in the development of PAH. Losartan, a specific angiotensin II receptor antagonist, is a well-known antihypertensive drug with a potential role in regulating angiotensin-converting enzyme-2 (ACE2), a recently found regulator of RAS. To determine the effect of losartan on smoke-induced PAH

Su-Xia Han; Guang-Ming He; Tao Wang; Lei Chen; Yun-Ye Ning; Feng Luo; Jin An; Ting Yang; Jia-Jia Dong; Zeng-lin Liao; Dan Xu; Fu-Qiang Wen

2010-01-01

353

Prophylactic treatment with telmisartan induces tissue-specific gene modulation favoring normal glucose homeostasis in Cohen-Rosenthal diabetic hypertensive rats.  

PubMed

The objectives were to assess the potential of long-term prophylactic administration of telmisartan, an angiotensin II receptor antagonist and a partial peroxisome proliferator activator receptor (PPAR)? agonist, in preventing the development of hypertension and hyperglycemia and to demonstrate the alteration in gene expression associated with the development of hyperglycemia and insulin resistance in Cohen-Rosenthal diabetic hypertensive rat, a unique model of hypertension and type 2 diabetes mellitus comorbidity. Cohen-Rosenthal diabetic hypertensive rats were continuously treated with telmisartan (3 mg/[kg d]) starting at age 6 to 8 weeks before developing hypertension or diabetes. Weight changes, blood pressure, blood insulin, adiponectin, glucose tolerance, and insulin sensitivity were monitored. Fat, liver, and muscle messenger RNAs were examined for the expression of genes potentially involved in the onset of insulin resistance. In addition to the expected antihypertensive effect of prophylactic telmisartan, diabetes was blunted, evidenced at the end of the study by a significantly lower glucose level. This was accompanied by improved glucose tolerance, increased sensitivity to insulin, reduction in fasting insulin levels and homeostasis model assessment index, as well as an increase in serum adiponectin. Telmisartan also prevented the increase in serum triglycerides and the associated appearance of lipid droplets in the liver. Diabetes induced tissue-specific changes in messenger RNAs expression of the following selected genes, which were restored by telmisartan treatment: PPAR?, PPAR?, PPAR? coactivator 1?, adiponectin, adiponectin receptor 1, adiponectin receptor 2, phosphotyrosine binding domain and a pleckstrin homology domain-containing adaptor protein, adenosine monophosphate kinase, and glucose translocator 4. Telmisartan blunted the development of hypertension, insulin resistance, and diabetes in prediabetic Cohen-Rosenthal diabetic hypertensive rats through pleiotropic activity, involving specific gene regulation of target organs. PMID:21820685

Younis, Firas; Oron, Yoram; Limor, Rona; Stern, Naftali; Rosenthal, Talma

2011-08-05

354

Prevention of hypertensive crises in rats induced by acute and chronic norepinephrine excess.  

PubMed

Calcium Channel Blockers (CCBs), competitive ?-adrenoceptor blockers, and phenoxybenzamine (POB) are used for preoperative treatment of pheochromocytomas. We analyzed the protection from hypertensive crisis provided by these drugs during acute and chronic norepinephrine excess. To ensure adaptive changes during chronic norepinephrine (NE) excess, we continuously exposed male Wistar rats to NE for 3 weeks (osmotic pumps). Afterwards, blood pressure (BP) was continuously measured while NE boli (0-1000 ?g/kg, i.?v.) were administered before and after antihypertensive treatment in anesthetized and catheterized rats. A single dose of urapidil (10 mg/kg), nitrendipine (600 ?g/kg) and POB (10 mg/kg) lowered BP from 212 ± 12 mmHg by 52 ± 7%, 31 ± 9%, and 50 ± 6%, respectively. With NE boli a maximum BP of 235 ± 29, 240 ± 30 and 138 ± 3 mmHg was measured in urapidil, nitrendipine, and POB treated animals (p<0.05). The number of hypertensive episodes (delta BP >30 mmHg) was 3 (3), 1.5 (0-3), and 0 (0-1) (p<0.05). Because of inferiority, urapidil was excluded from further testing. Chronically NE exposed rats were treated with POB (10 mg/kg/d), nifedipine (10 mg/kg/d), or vehicle for 7 days. Marked BP elevations were observed at baseline (167 ± 7, 210 ± 7 , and 217 ± 7 mmHg, p<0.01) and maximum blood pressure was 220 ± 32, 282 ± 26, and 268 ± 40 mmHg (p<0.001) with NE boli. Further stabilization was achieved combining POB pretreatment with a continuous nifedipine infusion, which effectively prevented BP elevations during NE excess. POB was the most effective drug used in monotherapy, but BP stabilization was superior using a combination of POB pretreatment with a continuous nifedipine infusion in this model. PMID:20665428

Weismann, D; Kleinbrahm, K; Hu, K; Fassnacht, M; Frantz, S; Ertl, G; Allolio, B; Maier, S K G

2010-07-27

355

Hypertension in pregnancy: New recommendations for managemen  

Microsoft Academic Search

Hypertension in pregnancy is a frequent complication that has substantial adverse perinatal outcomes. Hypertension may be\\u000a preexisting (chronic) essential or secondary hypertension; a second entity is pregnancy induced (gestational hypertension,\\u000a preeclampsia). Recent advances have identified newer markers for pregnancy hypertension: several potential candidate genes\\u000a may explain the apparent family inheritance of preeclampsia, and some thrombophilic markers hav been associated with

Roberta Shear; Line Leduc; Evelyne Rey; Jean-Marie Moutquin

1999-01-01

356

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

PubMed Central

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.

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

2011-01-01

357

Cytochrome P4501A1 is required for vascular dysfunction and hypertension induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin.  

PubMed

National Health and Nutrition Examination Survey data show an association between hypertension and exposure to dioxin-like halogenated aromatic hydrocarbons (HAHs). Furthermore, chronic exposure of mice to the prototypical HAH, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), induces reactive oxygen species (ROS), endothelial dysfunction, and hypertension. Because TCDD induces cytochrome P4501A1 (CYP1A1) and CYP1A1 can increase ROS, we tested the hypothesis that TCDD-induced endothelial dysfunction and hypertension are mediated by CYP1A1. CYP1A1 wild-type (WT) and knockout (KO) mice were fed one control or TCDD-containing pill (180 ng TCDD/kg, 5 days/week) for 35 days (n = 10-14/genotype/treatment). Blood pressure was monitored by radiotelemetry, and liver TCDD concentration, CYP1A1 induction, ROS, and aortic reactivity were measured at 35 days. TCDD accumulated to similar levels in livers of both genotypes. TCDD induced CYP1A1 in endothelium of aorta and mesentery without detectable expression in the vessel wall. TCDD also induced superoxide anion production, measured by NADPH-dependent lucigenin luminescence, in aorta, heart, and kidney of CYP1A1 WT mice but not KO mice. In contrast, TCDD induced hydrogen peroxide, measured by amplex red assay, to similar levels in aorta of CYP1A1 WT and KO mice but not in heart or kidney. TCDD reduced acetylcholine-dependent vasorelaxation in aortic rings of CYP1A1 WT mice but not in KO mice. Finally, TCDD steadily increased blood pressure after 15 days, which plateaued after 25 days (+20 mmHg) in CYP1A1 WT mice but failed to alter blood pressure in KO mice. These results demonstrate that CYP1A1 is required for TCDD-induced cardiovascular superoxide anion production, endothelial dysfunction, and hypertension. PMID:20634294

Kopf, Phillip G; Scott, Jason A; Agbor, Larry N; Boberg, Jason R; Elased, Khalid M; Huwe, Janice K; Walker, Mary K

2010-07-15

358

TRPV4 channel contributes to serotonin-induced pulmonary vasoconstriction and the enhanced vascular reactivity in chronic hypoxic pulmonary hypertension.  

PubMed

Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive channel in pulmonary arterial smooth muscle cells (PASMCs). Its upregulation by chronic hypoxia is associated with enhanced myogenic tone, and genetic deletion of trpv4 suppresses the development of chronic hypoxic pulmonary hypertension (CHPH). Here we further examine the roles of TRPV4 in agonist-induced pulmonary vasoconstriction and in the enhanced vasoreactivity in CHPH. Initial evaluation of TRPV4-selective antagonists HC-067047 and RN-1734 in KCl-contracted pulmonary arteries (PAs) of trpv4(-/-) mice found that submicromolar HC-067047 was devoid of off-target effect on pulmonary vasoconstriction. Inhibition of TRPV4 with 0.5 ?M HC-067047 significantly reduced the sensitivity of serotonin (5-HT)-induced contraction in wild-type (WT) PAs but had no effect on endothelin-1 or phenylephrine-activated response. Similar shift in the concentration-response curve of 5-HT was observed in trpv4(-/-) PAs, confirming specific TRPV4 contribution to 5-HT-induced vasoconstriction. 5-HT-induced Ca(2+) response was attenuated by HC-067047 in WT PASMCs but not in trpv4(-/-) PASMCs, suggesting TRPV4 is a major Ca(2+) pathway for 5-HT-induced Ca(2+) mobilization. Nifedipine also attenuated 5-HT-induced Ca(2+) response in WT PASMCs but did not cause further reduction in the presence of HC-067047, suggesting interdependence of TRPV4 and voltage-gated Ca(2+) channels in the 5-HT response. Chronic exposure (3-4 wk) of WT mice to 10% O2 caused significant increase in 5-HT-induced maximal contraction, which was partially reversed by HC-067047. In concordance, the enhancement of 5-HT-induced contraction was significantly reduced in PAs of CH trpv4(-/-) mice and HC-067047 had no further effect on the 5-HT induced response. These results suggest unequivocally that TRPV4 contributes to 5-HT-dependent pharmaco-mechanical coupling and plays a major role in the enhanced pulmonary vasoreactivity to 5-HT in CHPH. PMID:23739180

Xia, Yang; Fu, Zhenzhen; Hu, Jinxing; Huang, Chun; Paudel, Omkar; Cai, Shaoxi; Liedtke, Wolfgang; Sham, James S K

2013-06-05

359

Early life stress sensitizes rats to angiotensin II-induced hypertension and vascular inflammation in adult life.  

PubMed

Maternal separation during early life is an established chronic behavioral model of early life stress in rats. It is known that perinatal adverse environments increase activity of the renin-angiotensin (Ang) system, specifically Ang II, in adulthood. The aim of this study was to investigate whether the effects of early life stress augment the sensitivity of the Ang II pathway. Using Wistar Kyoto rats, the maternal separation (MS) protocol was performed by separating approximately half of the male pups from their mother 3 h/d from days 2 to 14 of life. Pups remaining with the mother at all times were used as controls. Maternal separation did not influence the plasma basal parameters, such as blood glucose, insulin, Ang II, Ang 1-7 and plasma renin activity. Furthermore, body weight, blood pressure, and heart rate were similar in MS and control rats. The acute pressor response to Ang II was not different in anesthetized MS and control rats. However, the chronic infusion of Ang II (65 ng/min SC) elicited an exaggerated hypertensive response in MS compared with control rats (P<0.05). Surprisingly, HR was dramatically increased during the second week of Ang II infusion in MS compared with control rats (P<0.05). This enhanced Ang II sensitivity was accompanied by a greater vascular inflammatory response in MS versus control rats. Chronic Ang II infusion increased vascular wall structure in both groups similarly. These data indicate that early life stress sensitizes rats to an increased hemodynamic and inflammatory response during Ang II-induced hypertension. PMID:20026758

Loria, Analia S; Pollock, David M; Pollock, Jennifer S

2009-12-21

360

Sildenafil reduces L-NAME-induced severe hypertension and worsening of myocardial ischaemia-reperfusion damage in the rat  

PubMed Central

Background and purpose: Phosphodiesterase-5 inhibitors are beneficial in pulmonary hypertension and congestive heart failure, the two conditions associated with coronary heart disease and ischaemia. We investigated whether sildenafil counteracts the cardiovascular alterations induced by N ?-nitro-L-arginine methyl ester (L-NAME) in the rat. Experimental approach: Sildenafil was given orally to rats at doses of 0.37, 0.75 or 1.5?mg kg?1day?1 for four weeks, either alone or with L-NAME (35-40?mg kg?1 day?1 in the drinking water). Systolic blood pressure and urinary parameters (6-keto-prostaglandin F1?, thromboxane B2, 8-isoprostane-prostaglandin F2? and nitrite/nitrate) were measured in conscious rats. Isolated hearts were subjected to low flow ischaemia–reperfusion, and myocardial levels of guanosine 3', 5'cyclic monophosphate (cGMP) were determined. Endothelial vascular dysfunction was examined in aortic rings. Key results: Sildenafil dose-dependently prevented the rise in systolic blood pressure in L-NAME-treated rats. This activity was associated with a normalization of urinary 8-isoprostane-prostaglandin F2? and other biochemical parameters. In perfused hearts, the post-ischaemic ventricular dysfunction was worse in preparations from L-NAME-treated rats than in controls. Sildenafil dose-dependently reduced this effect, and creatine kinase and lactate dehydrogenase release were lower too. cGMP levels, which were low in myocardial tissue from L-NAME-treated rats, were restored by sildenafil. In noradrenaline-precontracted aortic rings from L-NAME-treated rats acetylcholine lost its vasorelaxant effect, and sildenafil restored it. Conclusion and implications: In a rat model of chronic nitric oxide deprivation, where hypertension and aggravation of post-ischaemic ventricular dysfunction are associated with loss of vascular endothelium-relaxant function, sildenafil provided significant cardiovascular protection, primarily by maintaining tissue cGMP levels.

Rossoni, G; Manfredi, B; De Gennaro Colonna, V; Berti, M; Guazzi, M; Berti, F

2007-01-01

361

Endothelin-1-induced venous contraction is maintained in DOCA-salt hypertension; studies with receptor agonists  

PubMed Central

Deoxycorticosterone acetate (DOCA) salt hypertension is associated with an endothelin-1 (ET-1)-dependent increase in arterial resistance and mean circulatory filling pressure. Contraction of endothelium-intact arteries and veins from sham and DOCA-salt hypertensive rats to agonists of the ETA (ET-1(1–31)) and ETB receptor (sarafotoxin 6c; S6c) was investigated in tissue baths as was expression of mRNA for ET-1 and mRNA and protein for the ETA and ETB receptor. ET-1(1–31) contracted aorta and vena cava from sham rats with a 30 fold lower potency than ET-1. Contraction was not altered by the ETB receptor antagonist BQ788 (100 nM) but was abolished by the ETA receptor antagonist ABT-627 (30 nM). In DOCA-salt thoracic aorta, maximum contraction to ET-1 and ET-1(1–31) was reduced (36.6±6.3 and 13.3±4.4% of sham response, respectively); aorta did not contract to S6c. In vena cava from DOCA-salt rats, contraction to ET-1 and ET-1(1–31) was not reduced compared to sham contraction; vena cava from sham and DOCA-salt rats contracted to S6c with a similar potency. Real time RT–PCR revealed that prepro ET-1 mRNA was increased 6.6±3.3 fold and 8.7±3.9 fold greater in DOCA-salt aorta and vena cava, respectively, compared to sham. Vena cava expressed a higher content of ETA and ETB receptor mRNA than aorta (P<0.05), but no differences were observed between sham and DOCA-salt tissues. ETA and ETB receptor protein was identified in all tissues. Immunoreactive ETA receptor, observed as a 65, 30 and 28 kDa bands, was expressed 400% greater in DOCA-salt aorta compared to sham, but was not altered in vena cava. Immunoreactive ETB receptor, observed as 120, 45 and 30 kDa bands, tended to be higher in vena cava compared to aorta, but was not different in sham and DOCA-salt vena cava. These results suggest that ETA receptor function is impaired in aorta but not vena cava of DOCA-salt rats. The ETB receptor was present in the aorta but, unlike in veins, does not mediate contraction directly. A sustained response to ET-1 in the venous circulation may contribute to the elevated blood pressure in the DOCA-salt model.

Watts, Stephanie W; Fink, Gregory D; Northcott, Carrie A; Galligan, James J

2002-01-01

362

Gene therapy by targeted adenovirus-mediated knockdown of pulmonary endothelial Tph1 attenuates hypoxia-induced pulmonary hypertension.  

PubMed

Serotonin is produced by pulmonary arterial endothelial cells (PAEC) via tryptophan hydroxylase-1 (Tph1). Pathologically, serotonin acts on underlying pulmonary arterial cells, contributing to vascular remodeling associated with pulmonary arterial hypertension (PAH). The effects of hypoxia on PAEC-Tph1 activity are unknown. We investigated the potential of a gene therapy approach to PAH using selective inhibition of PAEC-Tph1 in vivo in a hypoxic model of PAH. We exposed cultured bovine pulmonary arterial smooth muscle cells (bPASMCs) to conditioned media from human PAECs (hPAECs) before and after hypoxic exposure. Serotonin levels were increased in hypoxic PAEC media. Conditioned media evoked bPASMC proliferation, which was greater with hypoxic PAEC media, via a serotonin-dependent mechanism. In vivo, adenoviral vectors targeted to PAECs (utilizing bispecific antibody to angiotensin-converting enzyme (ACE) as the selective targeting system) were used to deliver small hairpin Tph1 RNA sequences in rats. Hypoxic rats developed PAH and increased lung Tph1. PAEC-Tph1 expression and development of PAH were attenuated by our PAEC-Tph1 gene knockdown strategy. These results demonstrate that hypoxia induces Tph1 activity and selective knockdown of PAEC-Tph1 attenuates hypoxia-induced PAH in rats. Further investigation of pulmonary endothelial-specific Tph1 inhibition via gene interventions is warranted. PMID:22525513

Morecroft, Ian; White, Katie; Caruso, Paola; Nilsen, Margaret; Loughlin, Lynn; Alba, Raul; Reynolds, Paul N; Danilov, Sergei M; Baker, Andrew H; Maclean, Margaret R

2012-04-24

363

Gene Therapy by Targeted Adenovirus-mediated Knockdown of Pulmonary Endothelial Tph1 Attenuates Hypoxia-induced Pulmonary Hypertension  

PubMed Central

Serotonin is produced by pulmonary arterial endothelial cells (PAEC) via tryptophan hydroxylase-1 (Tph1). Pathologically, serotonin acts on underlying pulmonary arterial cells, contributing to vascular remodeling associated with pulmonary arterial hypertension (PAH). The effects of hypoxia on PAEC-Tph1 activity are unknown. We investigated the potential of a gene therapy approach to PAH using selective inhibition of PAEC-Tph1 in vivo in a hypoxic model of PAH. We exposed cultured bovine pulmonary arterial smooth muscle cells (bPASMCs) to conditioned media from human PAECs (hPAECs) before and after hypoxic exposure. Serotonin levels were increased in hypoxic PAEC media. Conditioned media evoked bPASMC proliferation, which was greater with hypoxic PAEC media, via a serotonin-dependent mechanism. In vivo, adenoviral vectors targeted to PAECs (utilizing bispecific antibody to angiotensin-converting enzyme (ACE) as the selective targeting system) were used to deliver small hairpin Tph1 RNA sequences in rats. Hypoxic rats developed PAH and increased lung Tph1. PAEC-Tph1 expression and development of PAH were attenuated by our PAEC-Tph1 gene knockdown strategy. These results demonstrate that hypoxia induces Tph1 activity and selective knockdown of PAEC-Tph1 attenuates hypoxia-induced PAH in rats. Further investigation of pulmonary endothelial-specific Tph1 inhibition via gene interventions is warranted.

Morecroft, Ian; White, Katie; Caruso, Paola; Nilsen, Margaret; Loughlin, Lynn; Alba, Raul; Reynolds, Paul N; Danilov, Sergei M; Baker, Andrew H; MacLean, Margaret R

2012-01-01

364

The beneficial impact of fasudil and sildenafil on monocrotaline-induced pulmonary hypertension in rats: a hemodynamic and biochemical study.  

PubMed

Pulmonary arterial hypertension (PAH) still cannot be cured effectively, hence the search for novel treatments continues. The effects of sildenafil (25 mg/kg body weight) and fasudil (30 mg/kg body weight) given alone or in combination, on normalization of right ventricular pressure (RVP), right ventricle mass, as well as the levels of several biomarkers (HDL-C, BNP, VEGF-A), were assessed in a rat model of monocrotaline (MCT)-induced PAH. MCT (60 mg/kg body weight) induced clear PAH in male Wistar rats. After 21 days, a significant decrease in RVP accompanied by a reduction of right ventricular hypertrophy - a significant decrease in the right ventricle/left ventricle plus septum ratio - as a result of sildenafil or fasudil administration was assessed. The administration of fasudil and sildenafil alone or in combination caused a significant decrease in plasma BNP level as compared to MCT-treated rats. Fasudil alone or with sildenafil, but not sildenafil alone, significantly increased HDL-C level as compared to MCT-treated rats. Fasudil and sildenafil given alone or in combination caused a significant increase in plasma VEGF-A level as compared to rats exposed to MCT. PMID:23428587

Jasi?ska-Stroschein, Magdalena; Owczarek, Jacek; ?uczak, Anna; Orszulak-Michalak, Daria

2013-02-21

365

Long-lasting hypotensive effect in renal hypertensive rats induced by nitric oxide released from a ruthenium complex.  

PubMed

In this study, we investigated the effect of the ruthenium complex [Ru(terpy)(bdq)NO] (TERPY) on the arterial pressure from renal hypertensive 2 kidney-1 clip (2K-1C) rats, which was compared with sodium nitroprusside (SNP). The most interesting finding was that the intravenous bolus injection of TERPY (2.5, 5.0, 7 mg/kg) had a dose-dependent hypotensive effect only in 2K-1C rats. On the other hand, SNP (35 and 70 ?g/kg) presented a similar hypotensive effect in both normotensive (2K) and 2K-1C although the effect of 70 ?g/kg was >35 ?g/kg. The injection of the nonselective NO-synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) increased the arterial pressure in 2K and 2K-1C rats with a similar magnitude. After infusion of L-NAME, the hypotensive effect induced by TERPY and SNP was potentiated in both 2K and in 2K-1C rats. The administration of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl increased the hypotensive effect induced by TERPY or SNP in both 2K and 2K-1C rats. The hypotensive effect induced by TERPY was longer than that produced by SNP. Taken together, our results show that the TERPY has a long-lasting hypotensive effect, which has a dose dependence and higher magnitude in 2K-1C compared with in 2K rats. In comparison with SNP, TERPY is less potent in inducing arterial pressure fall, but it presents a much longer hypotensive effect. PMID:22635073

Rodrigues, Gerson J; Pereira, Amanda C; Vercesi, Juliana A; Lima, Renata G; Silva, Roberto S; Bendhack, Lusiane M

2012-08-01

366

Hemodynamic, reflexive, and metabolic alterations induced by acute and chronic timolol therapy in hypertensive man.  

PubMed

The hemodynamic, cardiovascular, and metabolic effects of acute (intravenous) and prolonged (four weeks oral) timolol treatment were assessed in 16 patients with mild or moderate essential hypertension. Fifteen patients completed the outpatient study and ten showed a fall in mean arterial pressure of at least 10 mm Hg. They also demonstrated a significant fall in supine systolic (7%), diastolic (9%), and mean arterial pressure. Hemodynamic evaluation was performed in 13 patients and cardiac index was found to be reduced with both intravenous (20%) and oral timolol (13%). There was no correlation between the decrease in cardiac index and arterial pressure. Calculated total peripheral resistance rose with intravenous timolol and returned toward, but not below, pretreatment values with the oral therapy. Left ventricular ejection rate also fell significantly with intravenous timolol but returned toward pretreatment levels with oral therapy. Plasma renin activity was reduced similarly with both modes of administration and its reduction also did not correlate with the fall in arterial pressure. Plasma volume fell in eight of 13 patients. Reflexive responses to the Valsalva maneuver were considerably modified by both intravenous and oral timolol but responses to 50 degrees upright tilt and handgrip were not. Timolol is an effective oral antihypertensive agent with similar hemodynamic and metabolic effects to propranolol. PMID:618381

Dunn, F G; de Carvalho, J G; Frohlich, E D

1978-01-01

367

Diuretic induced long term hemodynamic changes in hypertension. A retrospective study in a MRFIT clinical center.  

PubMed

Retrospective analysis of hemodynamic factors was performed on hypertensive participants of our Multiple Risk Factor Intervention Trial (MRFIT) center to determine whether these may have a role in the higher mortality in a subgroup of special intervention (SI) participants with minor baseline electrocardiographic abnormalities. Stroke volume was estimated by a formula [SV = K(LVETxPP)x(1 + LVET/DP) where the K factor was determined using a separate group of individuals undergoing cardiac catheterization. The Pearson correlation between the two methods (dye dilution and above formula) was 0.7744 with a 95% confidence interval of 0.57-0.89 for the true correlation. In 222 SI and 186 usual care (UC) participants with no differences in stroke volume index (SVI) and cardiac output index (CI) at baseline, SVI and CI were systematically lower during the entire period of treatment in SI receiving higher average doses of thiazide diuretics. There was a moderate increase of SVI and CI in SI participants toward baseline after hydrochlorothiazide was replaced by other antihypertensive medication in the fourth year of the trial. We conclude that the lower SVI and CI could have been a contributing factor in the higher mortality in the SI group with ECG abnormalities resulting in decreased coronary flow reserve under stress conditions in these participants with probably pre-existing asymptomatic coronary artery disease. PMID:1600636

Kezdi, P; Kezdi, P C; Khamis, H J

1992-01-01

368

Multiple esophageal variceal ruptures with massive ascites due to myelofibrosis-induced portal hypertension  

PubMed Central

A 75-year old man had been diagnosed at 42 years of age as having polycythemia vera and had been monitored at another hospital. Progression of anemia had been recognized at about age 70, and the patient was thus referred to our center in 2008 where secondary myelofibrosis was diagnosed based on bone marrow biopsy findings. Hematemesis due to rupture of esophageal varices occurred in January and February of 2011. The bleeding was stopped by endoscopic variceal ligation. Furthermore, in March of the same year, hematemesis recurred and the patient was transported to our center. He was in irreversible hemorrhagic shock and died. The autopsy showed severe bone marrow fibrosis with mainly argyrophilic fibers, an observation consistent with myelofibrosis. The liver weighed 1856 g the spleen 1572 g, indicating marked hepatosplenomegaly. The liver and spleen both showed extramedullary hemopoiesis. Myelofibrosis is often complicated by portal hypertension and is occasionally associated with gastrointestinal hemorrhage due to esophageal varices. A patient diagnosed as having myelofibrosis needs to be screened for esophageal/gastric varices. Myelofibrosis has a poor prognosis. Therefore, it is necessary to carefully decide the therapeutic strategy in consideration of the patient’s concomitant conditions, treatment invasiveness and quality of life.

Tokai, Koichi; Miyatani, Hiroyuki; Yoshida, Yukio; Yamada, Shigeki

2012-01-01

369

Scanning electron microscopy of pulmonary vascular endothelium in rats with hypoxia-induced hypertension.  

PubMed

Scanning electron microscopy was used to study the endothelial surface of the pulmonary trunk, artery, and vein in normobaric control rats as well as in rats exposed to hypobaric hypoxia for 7 and 21 days. The individual endothelial cells of the normobaric pulmonary trunk and hilar artery were flat and slightly elongated with elevated nuclear regions, and those of the intermediate-sized artery were more elongated and had more microvilli than the large arteries studied. Their endothelial cell boundaries were outlined by beaded cytoplasmic projections. The surfaces of the normobaric hilar and intermediate-sized veins were smooth and demonstrated numerous longitudinal streaks. These venous endothelial cells were elongated and their cell boundaries were outlined by low discontinuous marginal folds. Exposure to hypobaric hypoxia caused the following changes on the arterial surface: elevation of the endothelial cells; formation of microvilli-rich cell clusters; formation of hollow defects; and the attachment of leukocytes. Hypobaric hypoxia also caused the disappearance of the longitudinal streaks and the occurrence of microvilli-rich cells in the hilar veins. The endothelial surface modifications in the hypobaric rats could be related to thickening of the endothelium, intimal edema, increased intimal connective tissue, luminal invasion of leukocytes, and increased endothelial cell proliferation, known to occur in systemic arteries of hypertensive animals. PMID:3739598

Hung, K S; McKenzie, J C; Mattioli, L; Klein, R M; Menon, C D; Poulose, A K

1986-01-01

370

Murine prolylcarboxypeptidase depletion induces vascular dysfunction with hypertension and faster arterial thrombosis  

PubMed Central

Prolylcarboxypeptidase (PRCP) activates prekallikrein to plasma kallikrein, leading to bradykinin liberation, and degrades angiotensin II. We now identify PRCP as a regulator of blood vessel homeostasis. ?-Galactosidase staining in PRCPgt/gt mice reveals expression in kidney and vasculature. Invasive telemetric monitorings show that PRCPgt/gt mice have significantly elevated blood pressure. PRCPgt/gt mice demonstrate shorter carotid artery occlusion times in 2 models, and their plasmas have increased thrombin generation times. Pharmacologic inhibition of PRCP with Z-Pro-Prolinal or plasma kallikrein with soybean trypsin inhibitor, Pro-Phe-Arg-chloromethylketone or PKSI 527 also shortens carotid artery occlusion times. Aortic and renal tissues have uncoupled eNOS and increased reactive oxygen species (ROS) in PRCPgt/gt mice as detected by dihydroethidium or Amplex Red fluorescence or lucigenin luminescence. The importance of ROS is evidenced by the fact that treatment of PRCPgt/gt mice with antioxidants (mitoTEMPO, apocynin, Tempol) abrogates the hypertensive, prothrombotic phenotype. Mechanistically, our studies reveal that PRCPgt/gt aortas express reduced levels of Kruppel-like factors 2 and 4, thrombomodulin, and eNOS mRNA, suggesting endothelial cell dysfunction. Further, PRCP siRNA treatment of endothelial cells shows increased ROS and uncoupled eNOS and decreased protein C activation because of thrombomodulin inactivation. Collectively, our studies identify PRCP as a novel regulator of vascular ROS and homeostasis.

Adams, Gregory N.; LaRusch, Gretchen A.; Stavrou, Evi; Zhou, Yihua; Nieman, Marvin T.; Jacobs, Gretta H.; Cui, Yingjie; Lu, Yuan; Jain, Mukesh K.; Mahdi, Fakhri; Shariat-Madar, Zia; Okada, Yoshio; D'Alecy, Louis G.

2011-01-01

371

Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension  

Microsoft Academic Search

monary arteries (PAs) of 6 patients with PAH and rats with monocrotaline-induced PAH, but not in the PAs of 3 patients and rats without PAH. Gene therapy with inhalation of an adenovirus carrying a phosphorylation- deficient survivin mutant with dominant-negative properties reversed established monocrotaline-induced PAH and prolonged survival by 25%. The survivin mutant lowered pulmonary vascular resistance, RV hyper- trophy,

M. Sean McMurtry; Stephen L. Archer; Dario C. Altieri; Sebastien Bonnet; Alois Haromy; Gwyneth Harry; Sandra Bonnet; Lakshmi Puttagunta; Evangelos D. Michelakis

2005-01-01

372

Endothelin mediates superoxide production in angiotensin II-induced hypertension in rats.  

PubMed

Angiotensin II and endothelin-1 (ET) are two hormones involved in cardiovascular diseases and well known for their capacity to induce free radical generation in vascular and cardiac tissues. In addition to its prooxidative effect, angiotensin II can increase the synthesis of ET-1 in vascular smooth muscle cells (VSMC). Our objective was to determine whether the ET-1 synthesis in VSMC is involved in angiotensin II-induced superoxide anion production in rats. Our results show that treatments of isolated VSMC with angiotensin II and ET increased superoxide. However, this increase occurred in a bimodal fashion for angiotensin II with a fast transient production (10 min) and a late sustained production (6 h), while ET-1 induced superoxide formation after a delay of 6 h. LU302872 and BQ-123, a nonselective and a selective ETA receptor antagonists, respectively, prevented angiotensin II-induced superoxide anion production only during the late phase. In contrast, BQ-3020, a selective ETB receptor antagonist, had no effect. In vivo, LU302872 reduced the aortic superoxide production induced by angiotensin II administered for 12 days. In conclusion, our results suggest that the superoxide generation induced by chronic angiotensin II infusion may be mediated by ET-1 acting on ETA receptors in VSMC in vitro. Furthermore, this effect appears to contribute to the excess superoxide production during the chronic activation of the renin-angiotensin system in vivo. PMID:15683715

Laplante, Marc-André; Wu, Rong; Moreau, Pierre; de Champlain, Jacques

2005-03-01

373

[Hypertension in pregnancy].  

PubMed

Hypertension in pregnancy is one of the main causes of maternal, fetal and newborn morbidity and mortality in civilised countries. Current recommendations of the European Society for Hypertension prefer definition of hypertension in pregnancy based on absolute values of blood pressure, i.e. systolic blood pressure > or = 140 mm Hg or diastolic blood pressure > or = 90 mm Hg. The most important task of classification of hypertension in pregnancy is to distinguish whether hypertension comes before pregnancy (the so called pre-existing hypertension) or whether it is a pregnancy-induced condition (the so called gestational hypertension). Pre-existing hypertension is diagnosed either before pregnancy or within the first 20 weeks of pregnancy. Gestational hypertension is characterised with poor blood circulation in many body organs, higher value of blood pressure usually being just one of the characteristic features. Non-pharmacological treatment of hypertension must be considered in pregnant women with systolic blood pressure 140-150 mm Hg or diastolic blood pressure 90-99 mm Hg. Salt restriction is not recommended, as well as weight reduction in obese women. Systolic blood pressure > or = 170 mm Hg or diastolic blood pressure > or = 110 mm Hg in pregnant women must be considered serious condition necessitating hospitalisation. Pharmacological therapy should include labetalol i.v. or metyldopa or nifedipin administered orally. Intravenous administration of dihydralazine is no longer a therapy of choice, for its use is connected with increased occurrence of adverse effects. The threshold values for commencement of anti-hypertension therapy are systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg in females with gestational hypertension without proteinuria or with pre-existing hypertension before commencement of 28th week of pregnancy. Drug administration to reduce hypertension is instituted after reaching the same threshold values in females with gestational hypertension and proteinuria or after occurrence of the symptoms any time during pregnancy, with the same threshold values of blood pressure in the case of pre-existing hypertension at the presence of accompanying diseases or organ malfunction and further in the case of pre-existing hypertension and gestational hypertension. In other cases drug treatment of hypertension is recommended at systolic blood pressure values of 150 mm Hg or diastolic blood pressure values of 95 mm Hg. Unless serious hypertension is involved, the drugs of choice include metyldope, labetalol, calcium channel blockers and beta-blockers. Calcium channel blockers are considered safe, unless administered concurrently with magnesium sulphate (risk of hypotension in the case of potential synergism). ACE inhibitors and angiotensine blockers II (AT1-blockers) are contraindicated in pregnancy. Treatment with diuretics is not substantiated, unless oliguria is present. I.v. magnesium sulphate is recommended for prevention of eclampsia and spasm treatment. PMID:16722158

Cífková, R

2006-03-01

374

Increased activity of the Na-K-ATPase in red cell-ghosts of patients with Cushing's Syndrome: Possible significance for the pathogenesis of glucocorticoid-induced hypertension  

Microsoft Academic Search

Zusammenfassung Bei 6 Patienten mit Cushing-Syndrom fand sich eine 3–4fach gesteigerte Aktivität der Na-K-ATPase in Erythrocytenmembranen im Vergleich zu 28 Kontrollpersonen (0.986±0.291 gegenüber 0.259±0.1 µM Pi·h-1·mg-1,p<0.001). Die Strophan-thininsensible Mg-ATPase war bei beiden Gruppen gleich. Der Befund spricht für eine Aktivierung der Natriumpumpe an den Zellmembranen von Patienten mit Glukokortikoidexceß.

G. Wambach; A. Helber; B. Allolio; W. Winkelmann; W. Kaufmann

1980-01-01

375

Long-term exposure to high-altitude chronic hypoxia during gestation induces neonatal pulmonary hypertension at sea level  

PubMed Central

We determined whether postnatal pulmonary hypertension induced by 70% of pregnancy at high altitude (HA) persists once the offspring return to sea level and investigated pulmonary vascular mechanisms operating under these circumstances. Pregnant ewes were divided into two groups: conception, pregnancy, and delivery at low altitude (580 m, LLL) and conception at low altitude, pregnancy at HA (3,600 m) from 30% of gestation until delivery, and return to lowland (LHL). Pulmonary arterial pressure (PAP) was measured in vivo. Vascular reactivity and morphometry were assessed in small pulmonary arteries (SPA). Protein expression of vascular mediators was determined. LHL lambs had higher basal PAP and a greater increment in PAP after NG-nitro-l-arginine methyl ester (20.9 ± 1.1 vs. 13.7 ± 0.5 mmHg; 39.9 ± 5.0 vs. 18.3 ± 1.3 mmHg, respectively). SPA from LHL had a greater maximal contraction to K+ (1.34 ± 0.05 vs. 1.16 ± 0.05 N/m), higher sensitivity to endothelin-1 and nitroprusside, and persistence of dilatation following blockade of soluble guanylate cyclase. The heart ratio of the right ventricle-to-left ventricle plus septum was higher in the LHL relative to LLL. The muscle area of SPA (29.3 ± 2.9 vs. 21.1 ± 1.7%) and the protein expression of endothelial nitric oxide synthase (1.7 ± 0.1 vs. 1.1 ± 0.2), phosphodiesterase (1.4 ± 0.1 vs. 0.7 ± 0.1), and Ca2+-activated K+ channel (0.76 ± 0.16 vs. 0.30 ± 0.01) were greater in LHL compared with LLL lambs. In contrast, LHL had decreased heme oxygenase-1 expression (0.82 ± 0.26 vs. 2.22 ± 0.44) and carbon monoxide production (all P < 0.05). Postnatal pulmonary hypertension induced by 70% of pregnancy at HA promotes cardiopulmonary remodeling that persists at sea level.

Herrera, Emilio A.; Riquelme, Raquel A.; Ebensperger, German; Reyes, Roberto V.; Ulloa, Cesar E.; Cabello, Gertrudis; Krause, Bernardo J.; Parer, Julian T.; Giussani, Dino A.

2010-01-01

376

Influence of aminoguanidine, an inhibitor of inducible nitric oxide synthase, on the pulmonary hypertensive response to microparticle injections in broilers.  

PubMed

The pulmonary hypertensive response to pulmonary vascular obstruction caused by intravenously injected microparticles is amplified by pretreatment with N(omega)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 [endothelial NO synthase (eNOS or NOS-3)] and inducible [inducible NO synthase (iNOS or NOS-2)] forms of NO synthase. In the present study we used the selective iNOS inhibitor aminoguanidine (AG) to evaluate the role of iNOS in modulating the pulmonary hypertension (PH) triggered by microparticle injections. Experiment 1 was conducted to confirm the ability of AG to inhibit NO synthesis by iNOS in broiler peripheral blood mononuclear cells exposed to bacterial lipopolysaccharide (LPS, endotoxin). Mononuclear leukocytes treated with LPS produced 10-fold more NO than untreated (control) cells. The LPS-stimulated production of NO was partially inhibited by L-NAME and was fully inhibited by AG, thereby confirming that AG inhibits LPS-mediated iNOS activation in broilers. In Experiment 2 we evaluated the responses of male progeny from a base population (MP Base) and from a derivative line selected for one generation from the survivors of an LD50 microparticle injection (MP Select). The pulmonary arterial pressure (PAP) was lower in MP Select than in MP Base broilers. Both lines exhibited similar percentage increases in PAP after microparticles were injected, and AG modestly amplified the PH triggered by microparticles in both lines. In Experiment 3 we evaluated the responses of male progeny from a second base population (PAC Base) and from a derivative line selected for 3 generations using the unilateral pulmonary artery clamp technique (PAC Select). The PAP was lower in PAC Select than in PAC Base broilers, and both lines exhibited similar percentage increases in PAP in response to the microparticles. The PH triggered by microparticles was not amplified by AG but was doubled by L-NAME. These experiments demonstrate that during the 30 min following pulmonary vascular entrapment of microparticles, iNOS modulated the PH elicited in broilers derived from the MP pedigree line, but not in broilers from the PAC pedigree line. Different NOS-mediated responses among broiler populations may affect pulmonary hemodynamic characteristics of broiler lines selected using i.v. microparticle injections. PMID:16553284

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

2006-03-01

377

[Management of resistant hypertension].  

PubMed

High blood pressure is one of the leading factors influencing the cardiovascular risk. Despite current knowledge on the management of hypertension and the numerous antihypertensive drugs available, hypertension remains insufficiently controlled and part of these "uncontrolled" patients meet the definition of resistant hypertension. Resistant hypertension is defined by the failure of lowering blood pressure values to blood pressure target (office blood pressure < 140/90 or 130/80 mmHg in patients with diabetes or chronic kidney disease) despite appropriate treatment with optimal doses of three antihypertensive drugs from three different classes, one of which is a diuretic. Pseudoresistance should be excluded by using 24h ambulatory blood pressure or home blood pressure. The management of resistant hypertension includes the screening of secondary forms of hypertension and the identification of life style factors such as obesity, excessive alcohol and dietary sodium intake, volume overload, drug-induced hypertension. The treatment associates lifestyle changes, discontinuation of interfering substances, association of antihypertensive drugs on top of the initial triple therapy (including diuretic, blockers of the renin-angiotensin system and calcium channel blockers) ie aldosterone antagonists as fourth line treatment. New device-based approaches aiming to decrease the sympathetic tone including renal denervation and baroreceptor stimulation are under development. PMID:23789498

Briet, Marie; Bobrie, Guillaume; Azizi, Michel

2013-05-01

378

Hyperinsulinemia induces myocardial infarctions and arteriolar medial hypertrophy in spontaneously hypertensive rats.  

PubMed

To investigate the effects of hyperinsulinemia on the myocardial vessels, long acting insulin (mixtard, a combination of 30% regular human insulin and 70% NPH human insulin) was injected daily for 8 weeks, intraperitoneally, in two strains of rats, normotensive WKY and hypertensive SHR. There were four groups in all, a control group, and an insulin-injected group in each strain. The drinking water contained 10% glucose to prevent hypoglycemia in the insulin-injected rats. At the end of the 8 weeks experimental period, after measuring blood pressure and taking blood for the determination of glucose, urea, creatinine, and insulin, the rats were killed. The organs were fixed in formaldehyde. The blood glucose levels were higher at the end of the experiment, in both the placebo- (saline)-injected and the insulin-injected rats. Blood pressure rose significantly only in the insulin-injected SHR. The intramyocardial arterioles in the insulin-injected SHR had a significantly thicker vascular wall than the placebo-injected SHR, as represented by the vessel wall to lumen ratio, because of hypertrophy of the media. When compared with the placebo injected WKY rats, there was a higher wall/lumen ratio of the intramyocardial arterioles in the insulin-injected WKY, but the difference did not reach significance. Heart weights factored by body weights was significantly higher in insulin-injected as compared with placebo-injected SHR. Myocardial infarctions were observed in four of eight rats in the insulin-injected SHR group despite the fact that there were no signs of atherosclerosis or intimal thickening. It is possible that the increase in heart weight and the probable increase in metabolic activity resulting from hype