endothelin-1 and Hypertension--Renovascular

In the present study, we used a two-kidney-two-clip (2k2c) stroke-prone renovascular hypertension rat model (RHRSP) to investigate the protective effects of ligustrazine (TMP) on cerebral arteries and to examine PI3K/Akt pathway behavior under this protection.. The cerebral artery remodeling was induced by 2k2c-induced renovascular hypertension. Brain basilar artery tissues were isolated and their histological changes were detected through H&E and EVG staining, α-SMA IHC staining, and transmission electron microscopy at four, eight, and twelve weeks after 2k2c surgery, both with and without TMP treatment. Meanwhile, the ET-1, Ang II, and NO levels in basilar arteries and plasma were determined. Furthermore, the PTEN expression and the activation of PI3K/Akt in basilar artery tissues were detected through IHC and Western Blot. In addition, the primary basilar artery smooth muscle cells (BASMCs) were cultured and TMP protection of BASMCs stimulated with ET-1/Ang II in the presence or absence of insulin-like growth factor 1 (IGF-1) was determined.. TMP attenuated basilar artery remodeling, decreased ET-1 and Ang II levels and increased NO level in basilar arteries and plasma of RHRSP rats. Moreover, TMP reduced BASMCs proliferation upon ET-1/Ang II stimulation. We also found that TMP could effectively suppress the activation of PI3K/Akt in 2k2c-RHRSP rat basilar artery and ET-1/Ang II stimulated BASMCs. Most importantly, IGF-1, as an activator of PI3K/Akt, could damage the protective effect of TMP.. TMP exerts its protective effects and prevents basilar artery remodeling in RHRSP rats at least partly through the inhibition of PI3K/Akt pathway.

Topics: Angiotensin II; Animals; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Endothelin-1; Hypertension, Renovascular; Ligation; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Nitric Oxide; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Pyrazines; Rats, Sprague-Dawley; Renal Artery; Signal Transduction; Temporal Arteries; Vascular Remodeling

Basilar vascular smooth muscle cells (BASMCs) hyperplasia is a prominent feature of cerebrovascular remodeling and stroke during the development of hypertension. Tanshinone IIA (Tan) has been reported to exhibit a protective effect against the pathological features of hypertension. Previous studies have shown that phosphoinostitide-3 kinase (PI3K)/3'-phosphoinostitide dependent kinase (PDK1)/AKT pathway is involved in the regulation of proliferation of various cell types. Therefore, there may be a crosstalk between Tan antihypertension processes and PI3K/PDK1/AKT proliferative effect in BASMCs. To test this hypothesis, we used a 2-kidney, 2-clip hypertension model to examine the effect of Tan on PI3K/PDK1/AKT pathway by cellular, molecular, and biochemical approaches. Our results revealed that the abundance of PDK1 in plasma was paralleled with an increase in blood pressure and the cross-sectional area of basilar artery in hypertensive rats. Tan decreased blood pressure and hypertension-induced PDK1 phosphorylation but produced no effect on the phosphorylation of PI3K. Moreover, Tan attenuated endothelin 1 induced the activation of PDK1/AKT pathway in rat BASMCs. Tan could inhibit cell cycle transition by regulating the expression of cyclin D1 and p27, in turn, prevent proliferation of BASMCs. Our study provides a novel mechanism by which Tan prevents cerebrovascular cell proliferation during hypertension, and thus Tan may be a potential therapeutic agent for cerebrovascular remodeling and stroke.

Topics: Animals; Basilar Artery; Benzofurans; Blood Pressure; Cell Cycle; Cell Proliferation; Cyclin D1; Cyclin-Dependent Kinase Inhibitor p27; Endothelin-1; Hypertension; Hypertension, Renovascular; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phosphorylation; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Rats; Rats, Sprague-Dawley

We hypothesized that chronic specific endothelin-A (ET-A) receptor blockade therapy would reverse renal dysfunction and injury in advanced experimental renovascular disease. To test this, unilateral renovascular disease was induced in 19 pigs, and after 6 weeks, single-kidney hemodynamics and function was quantified in vivo using computed tomography. All pigs with renovascular disease were divided such that seven were untreated, seven were treated with ET-A blockers, and five were treated with ET-B blockers. Four weeks later, all pigs were restudied in vivo, and then killed and ex vivo studies performed on the stenotic kidney to quantify microvascular density, remodeling, renal oxidative stress, inflammation, and fibrosis. Renal blood flow, glomerular filtration rate, and redox status were significantly improved in the stenotic kidney after ET-A but not ET-B blockade. Furthermore, only ET-A blockade therapy reversed renal microvascular rarefaction and diminished remodeling, which was accompanied by a marked decreased in renal inflammatory and fibrogenic activity. Thus, ET-A but not ET-B blockade ameliorated renal injury in pigs with advanced renovascular disease by stimulating microvascular proliferation and decreasing the progression of microvascular remodeling, renal inflammation, and fibrosis in the stenotic kidney. These effects were functionally consequential as ET-A blockade improved single kidney microvascular endothelial function, renal blood flow, and glomerular filtration rate, and decreased albuminuria.

Topics: Animals; Biomarkers; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelin-1; Hypertension, Renovascular; Kidney; Microvessels; Multidetector Computed Tomography; Renal Artery Obstruction; Renal Circulation; Swine

Dioscorea opposita Thunb. (Huai Shan Yao, DOT), a common staple food in China, has been used for more than 2000 years in traditional Chinese medicine (TCM) to treat different systemic diseases including hypertension. The objective of this study was to investigate the possible antihypertensive effects of the aqueous extract of (DOT) in renovascular hypertensive rats as well as the mechanism in reducing blood pressure.. The two-kidney one-clip (2K1C) Goldblatt model of renovascular hypertension was used in Wistar rats. Rats with captopril, low-dose DOT and high-dose DOT treated 2K1C groups for 6 weeks. The blood pressure, cardiac mass index (heart weight/body weight), plasma level of angiotensin-II (Ang-II), endothelin-1(ET-1), superoxide dismutase (SOD) and malondialdehyde (MDA) were evaluated.. DOT significantly reduced mean systolic and diastolic blood pressure after treatment. DOT also significantly increased plasma SOD activity but decreased plasma MDA concentration. Renal function was improved with captopril and DOT. DOT reduced plasma Ang-II activity and plasma ET concentration. They couldalso significantly reduce the left ventricular hypertrophy and cardiac mass index.. Our results suggest that DOT may have an antihypertensive effect on hypertension by inhibit ET-converting enzyme and antioxidant activity, which warrant further exploration.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Antioxidants; Blood Pressure; Captopril; China; Dioscorea; Drugs, Chinese Herbal; Endothelin-1; Heart; Hypertension; Hypertension, Renovascular; Hypertrophy, Left Ventricular; Kidney; Male; Malondialdehyde; Oxidative Stress; Phytotherapy; Rats, Sprague-Dawley; Rats, Wistar; Superoxide Dismutase

The aim of the study was to evaluate the effect of chronic inhibition of endothelin-1 (ET-1) synthesis on renovascular hypertension development. Male Wistar rats were subjected to an operation, according to the "1 kidney, 1 clip" method and were given an endothelin-converting enzyme inhibitor PP36 per os with drinking water for 4 weeks. Serum urea rose by 21% in hypertensive rats and by 44% in PP36 treated hypertensive rats. PP36 treatment resulted in blood pressure rise both in the Sham group (compared to the initial blood pressure level) and in hypertensive rats (compared to hypertensive control group). Significant reduction of circulating ET-1 after chronic PP36 administration by 28% was obtained only in normotensive, but not hypertensive rats. Circulating ET-1 was not altered in hypertensive rats, but ET-1 excretion rate was significantly enhanced by 90%, which was abolished by PP36. We suggest that chronic reduction of ET-1 synthesis in the kidney might lead to water and salt retention.

Topics: Animals; Aspartic Acid Endopeptidases; Deoxyuridine; Endothelin-1; Endothelin-Converting Enzymes; Hypertension, Renovascular; Kidney; Male; Metalloendopeptidases; Microsurgery; Propanolamines; Rats; Rats, Wistar; Renin-Angiotensin System; Salts; Urea; Water

Ocimum basilicum L. (OBL), sweet basil, is a medicinal herb used in traditional Chinese medicine to treat cardiovascular diseases including hypertension. The objective of the study was to investigate the possible antihypertensive effects of OBL extract in renovascular hypertensive rats. The two-kidney one-clip (2K1C) Goldblatt model of renovascular hypertension was used in Wistar rats. Rats were randomized into sham, untreated 2K1C, captopril- (30 mg kg(-1) per day orally) and OBL- (100, 200, 400 mg kg(-1) per day orally) (low (L)-, medium (M)-, high (H)-OBL) treated 2K1C groups (n=10-12 per group), followed up for 4 weeks. Blood pressure, heart weight/body weight, plasma angiotensin-II and endothelin (ET)-1 were studied. OBL reduced systolic and diastolic blood pressure by about 20 and 15 mm Hg, respectively, compared with 35 and 22 mm Hg for captopril, from the lowest dose tested with no dose dependency. Cardiac hypertrophy was reduced from 3.6+/-0.7 mg g(-1) for untreated 2K1C to 3.0+/-0.6, 2.9+/-0.6 and 2.4+/-0.4 mg g(-1) for L-, M- and H-OBL, respectively, compared with 2.6+/-0.5 for sham and 3.1+/-0.4 mg g(-1) for captopril (P<0.05). Renal function was improved with captopril. Angiotensin was reduced to a lesser extent than with captopril. ET was reduced to lower concentrations (78+/-15, 80+/-22, 82+/-15 pg ml(-1) for L-, M-, H-OBL, respectively) than in sham (116+/-31 pg ml(-1)), untreated 2K1C (174+/-72 pg ml(-1)) or captopril (117+/-72 pg ml(-1)) groups. The effects of OBL on blood pressure, cardiac hypertrophy and ET, are consistent with an effect on ET-converting enzyme, and warrant further exploration.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Aspartic Acid Endopeptidases; Blood Pressure; Captopril; Cardiomegaly; Disease Models, Animal; Endothelin-1; Endothelin-Converting Enzymes; Hypertension, Renovascular; Kidney; Male; Metalloendopeptidases; Ocimum basilicum; Plant Extracts; Rats; Rats, Wistar

The total saponins of Panax notoginseng have been clinically used for the treatment of cardiovascular diseases and stroke in China. Our recent study has identified ginsenoside-Rd, a purified component of total saponins of P. notoginseng, as an inhibitor to remarkably inhibit voltage-independent Ca(2+) entry. We deduced a hypothesis that the inhibition of voltage-independent Ca(2+) entry might contribute to its cerebrovascular benefits. Ginsenoside-Rd was administered to two-kidney, two-clip (2k2c) stroke-prone hypertensive rats to examine its effects on blood pressure, cerebrovascular remodeling and Ca(2+) entry in freshly isolated basilar arterial vascular smooth muscle cells (BAVSMCs). Its effects on endothelin-1 induced Ca(2+) entry and cellular proliferation were assessed in cultured BAVSMCs. The results showed that, in vivo, ginsenoside-Rd treatment attenuated basilar hypertrophic inward remodeling in 2k2c hypertensive rats without affecting systemic blood pressure.During the development of hypertension, there were time-dependent increases in receptor-operated Ca(2+) channel (ROCC)-, store-operated Ca(2+) channel (SOCC)- and voltage dependent Ca(2+) channel (VDCC)-mediated Ca(2+) entries in freshly isolated BAVSMCs. Ginsenoside-Rd reversed the increase in SOCC- or ROCC- but not VDCC-mediated Ca(2+) entry. In vitro, ginsenoside-Rd concentration-dependently inhibited endothelin-1 induced BAVSMC proliferation and Mn(2+) quenching rate within the same concentration range as required for inhibition of increased SOCC- or ROCC-mediated Ca(2+) entries during hypertension. These results provide in vivo evidence showing attenuation of hypertensive cerebrovascular remodeling after ginsenoside-Rd treatment. The underlying mechanism might be associated with inhibitory effects of ginsenoside-Rd on voltage-independent Ca(2+) entry and BAVSMC proliferation, but not with VDCC-mediated Ca(2+) entry.

Topics: Animals; Basilar Artery; Blood Pressure; Brain; Calcium; Calcium Channel Blockers; Cell Proliferation; Electric Conductivity; Endothelin-1; Ginsenosides; Hypertension, Renovascular; Male; Microscopy, Electron, Transmission; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Stroke

To assess the value of renal vein renin , plasma endothelin (ET), nitric oxide (NO), calcitonin gene-related peptide (CGRP) in predicting the therapeutic effect of percutaneous renal artery stenting.. Selective renal angiography was performed in 60 patients with coronary artery disease and hypertension. All the patients with obvious unilateral renal artery stenosis (lumen narrowing >or =50%) underwent percutaneous transluminal renal angioplasty and stenting. Bilateral renal vein and inferior vena cava plasma renin activity (PRA) and plasma ET, NO, and CGRP levels were measured and the two-year follow-up data of the patients analyzed.. In all the patients, PRA in the ischemic kidney was significantly higher than that in the contralateral kidney (3.89-/+3.14 vs 2.01-/+1.93 nmol/L/h, P>0.05). After renal artery revascularization with stenting, PRA in the ischemic kidney was reduced obviously (P<0.05), which was significantly lower in patients with renal vein renin ratio (RVRR)>1.5 than in those with RVRR <1.5 (1.92-/+2.15 vs 2.42-/+0.56 nmol/L/h, P<0.05]. Plasma ET level was significantly higher, whereas plasma NO level significantly lower in patients with PVRR>1.5 (P<0.05). Greater improvement of blood pressure was observed in patients with RVRR>1.5 after two years than in those with RVRR< 1.5 (P<0.05).. The activity of penal vein renin, plasma ET, NO, and CGRP may provide valuable information for predicting the therapeutic effect of percutaneous renal artery stenting.

Topics: Aged; Angioplasty, Balloon; Calcitonin Gene-Related Peptide; Endothelin-1; Female; Humans; Hypertension, Renovascular; Male; Middle Aged; Nitric Oxide; Radiography; Renal Artery; Renal Artery Obstruction; Renal Veins; Renin; Stents

1. The present study was designed to investigate the haemodynamic features and morphological changes in experimentally hypertensive rat models. 2. Sprague-Dawley rats were used to prepare the experimentally hypertensive models, including two-kidney, one-clip renovascular hypertensive (2K1C) rats, deoxycorticosterone acetate salt hypertensive (DOCA) rats and N(G)-nitro-l-arginine methyl ester-induced hypertensive (l-NAME) rats. Six weeks after the induction of hypertension, 24 h blood pressure was recorded and blood pressure variability (BPV) expressed by 24 h (or 12 h in the daytime and night-time study) standard deviation of the variables was calculated. Then, cardiac baroreflex sensitivity (BRS) was determined and four endogenous factors (tumour necrosis factor-alpha, interleukin-1beta, angiotensin II and endothelin-1) were measured. Finally, morphological changes were examined. 3. It was found that an increase in BPV and a decrease in BRS were accompanied by an elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV, whereas the l-NAME rats had the lowest BRS. 4. Morphological changes were similar in DOCA and l-NAME rats and the cardiac changes were relatively slight in 2K1C rats. Tumour necrosis factor-alpha was increased in all the three models, especially in DOCA rats. Endothelin-1 was higher in DOCA rats and angiotensin II was increased in 2K1C rats and decreased in DOCA rats. 5. In conclusion, increased BPV and decreased BRS accompanied the elevation of blood pressure in all three hypertensive models. The DOCA rats had the highest BPV and the l-NAME rats had the lowest BRS. Obvious organ damage was seen in all three hypertensive models 6 weeks after the induction of hypertension.

Topics: Angiotensin II; Animals; Baroreflex; Blood Pressure; Blood Pressure Determination; Desoxycorticosterone; Disease Models, Animal; Endothelin-1; Hypertension; Hypertension, Renovascular; Interleukin-1; Kidney Glomerulus; Male; Myocardium; NG-Nitroarginine Methyl Ester; Organ Size; Rats; Rats, Sprague-Dawley; Time Factors; Tumor Necrosis Factor-alpha

Accumulation of interstitial collagen (fibrosis) between the endothelium and myocytes is one of the hallmarks of cardiac failure in renovascular hypertension (RVH). Renal insufficiency increases plasma homocysteine (Hcy), and levels of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) are inversely related to plasma Hcy levels. We hypothesize that in RVH, accumulation of collagen between the endothelium and myocytes leads to endothelial-myocyte disconnection and uncoupling, in part, by hyperhomocysteinemia. Furthermore, we hypothesize that Hcy increases reactive oxygen species, generates nitrotyrosine, activates latent matrix metalloproteinase, and decreases the levels of endothelial nitric oxide in response to antagonizing PPAR-gamma. To create RVH in mice, the left renal artery was clipped with 0.4-mm silver wire for the 2 kidney, 1 clip (2K1C) method. Sham surgery was used as a control. To induce PPAR-gamma, 8 microg/mL ciglitazone (CZ) was administered to drinking water 2 days before surgery and continued for 4 weeks. Mice were grouped as 2K1C, sham, 2K1C+CZ, or sham+CZ (n = 6 in each group). Plasma Hcy increased 2-fold in the 2K1C-treated group (p < 0.05) as compared with the sham, and CZ had no effect on Hcy levels as compared to the 2K1C-treated group. Hcy binding in cardiac tissue homogenates decreased in the 2K1C-treated group but was substantially higher in the CZ-treated group. Cardiac reactive oxygen species levels were increased and endothelial nitric oxide were decreased in the 2K1C-treated group. Matrix metalloproteinase-2 and -9 activities were increased in the 2K1C-treated group compared with the control. Levels of cardiac inhibitor of metalloproteinase were decreased, whereas there was no change in tissue inhibitor of metalloproteinase-1 expression in the 2K1C-treated group vs. the sham-treated group. Collagen and nitrotyrosine levels were increased in the 2K1C-treated group, but mice treated with CZ showed lower levels comparatively. Cardiac transferase deoxyuridine nick-end labeling-positive cells were increased, and muscle cells were impaired in the 2K1C-treated mice vs. the sham-control mice. This was associated with decreased acetylcholine and bradykinin responses, which suggests endothelial-myocyte uncoupling in 2K1C-treated mice. Our results suggest that fibrosis between the endothelium and myocytes leads to an endothelial-myocyte disconnection and uncoupling by Hcy accumulation secondary to increased reactive oxygen s

Topics: Acetylcholine; Animals; Blotting, Western; Collagen; Endothelin-1; Endothelium, Vascular; Fibrosis; Homocysteine; Hypertension, Renovascular; Hypoglycemic Agents; Kidney; Male; Matrix Metalloproteinases; Mice; Mice, Inbred C57BL; Myocardial Contraction; Myocytes, Cardiac; Nitroprusside; PPAR gamma; Proteinuria; Thiazolidinediones; Tissue Inhibitor of Metalloproteinase-1; Tyrosine; Vasodilator Agents; Ventricular Remodeling

Leukocyte adhesion to endothelial cells plays a key role in inflammatory processes associated with end-organ injury. Endothelin-1 (ET-1), which stimulates inflammatory processes, contributes to cardiovascular damage in deoxycorticosterone (DOCA)-salt hypertension. We investigated whether ETA receptor blockade modulates in vivo leukocyte-endothelial cell interactions and expression of cell adhesion molecules (CAM) involved in these processes. DOCA-salt and control uninephrectomized rats were treated with the ETA antagonist BMS182874 (40 mg/kg per day) or vehicle. Analysis of CAMs expression by reverse transcription-polymerase chain reaction and immunohistochemistry showed increased cardiac platelet selectin (P-selectin), detected mainly in endothelial cells, and vascular cell adhesion molecule-1 (VCAM-1), but not intercellular adhesion molecule-1 (ICAM-1), in DOCA-salt rats. Cardiac expression of endothelial selectin (E-selectin) was decreased, whereas immunoreactivity to ED-1 and myeloperoxidase (MPO) activity, markers of macrophage and leukocyte infiltration, respectively, were increased in DOCA-salt. Leukocyte-endothelial cell interaction, functionally assessed in venules of internal spermatic fascia by intravital microscopy, was significantly altered in DOCA-salt rats as evidenced by increased leukocyte adhesion and decreased rolling. BMS182874 treatment normalized leukocyte-endothelium interactions, decreased cardiac VCAM-1 expression in DOCA and control groups, and had no effects on ICAM-1 expression. BMS182874 also increased E-selectin and abolished P-selectin expression in DOCA-salt, but not in control rats. The ETA antagonist reduced cardiac ED-1 content and MPO activity and prevented cardiac damage in DOCA-salt rats. These data indicate that ET-1 participates, via activation of ETA receptors, in altered leukocyte-endothelial cell interactions in DOCA-salt rats, possibly by modulating expression of CAMs, and that the inflammatory status is associated with cardiac damage in mineralocorticoid hypertension.

Topics: Animals; Cell Adhesion; Cell Adhesion Molecules; Chemotaxis, Leukocyte; Dansyl Compounds; Desoxycorticosterone; Disease Models, Animal; E-Selectin; Endothelin A Receptor Antagonists; Endothelin-1; Endothelium, Vascular; Gene Expression Regulation; Hypertension; Hypertension, Renovascular; Inflammation; Intercellular Adhesion Molecule-1; Leukocytes; Macrophages; Male; Myocardium; Nephrectomy; P-Selectin; Rats; Rats, Wistar; Receptor, Endothelin A; Reverse Transcriptase Polymerase Chain Reaction; Sodium Chloride, Dietary; Vascular Cell Adhesion Molecule-1

Coronary endothelial dysfunction is associated with an increase in cardiac events. Hypercholesterolemia (HC) and hypertension (HT) are both associated with endothelial dysfunction, and their coexistence is associated with an increased incidence of cardiac events in epidemiological studies. However, pathogenic mechanisms are poorly understood. Here we studied the effects of coexisting HC and HT on coronary endothelial function.. Four groups of pigs were studied after 12 weeks of a normal diet (n=9), a 2% HC diet (n=9), HT (achieved by unilateral renal artery stenosis, n=8), or HC+HT (n=6). Coronary endothelial function was tested, in epicardial arteries and arterioles, by using organ chamber techniques. Oxidative stress was measured in coronary artery tissue. Vasodilatory response to bradykinin and calcium ionophore was significantly impaired in animals with HC+HT compared with each risk factor alone (P<0.05 for both). In animals with coexistent HC and HT, the increase in oxidative stress was more pronounced compared with each risk factor alone (P<0.05). Furthermore, chronic antioxidant supplementation significantly improved coronary artery vasoreactivity.. These results suggest that HC and HT have a synergistic deleterious effect on coronary endothelial function, associated with increased oxidative stress. This interaction may contribute to the increased incidence of coronary heart disease and cardiac events seen when HC and HT coexist.

Topics: Animals; Antioxidants; Ascorbic Acid; Bradykinin; Calcimycin; Coronary Artery Disease; Coronary Vessels; Cyclic GMP; Diet, Atherogenic; Endothelin-1; Endothelium, Vascular; Female; Hemodynamics; Hypercholesterolemia; Hypertension, Renovascular; Lipids; Nitric Oxide; Nitroprusside; Oxidative Stress; Renal Artery Obstruction; Renin; Substance P; Swine; Vasodilator Agents; Vitamin E

Increased expression of the cardiac natriuretic peptides (NP), atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) is observed during chronic hemodynamic overload. The mechanisms underlying this process are not fully understood. In vitro, endothelin 1 (ET-1) is a powerful stimulator of cardiac NP and, therefore, has been assumed to be one possible mediator of increased NP gene expression following chronic pressure or volume overload. In the present work we investigated the possible role of ET-1 in mediating the observed upregulation of cardiac NP in two kidney-one clip (2K-1C) Goldblatt hypertensive rats treated for 6 weeks with the ET-1 type A (ET(A)) receptor subtype receptor antagonist ABT-627.. 2K-1C hypertension was induced in male Sprague-Dawley rats weighing 100-125 g by placing a silver clip (internal diameter 0.25 mm) around the left renal artery through a flank incision. The right kidney was left undisturbed. Sham operated rats underwent the same experimental procedures but no clip was placed on the left renal artery. ABT-627 was administered (10 mg/kg per day) in the drinking water for 6 weeks.. In hypertensive rats, ABT-627 prevented a further rise in blood pressure beginning at 3 weeks after clipping and reduced the ventricular hypertrophy observed at the end of the experiment. ET(A) blockade prevented enhanced NP gene expression in the right ventricle and partially prevented it in the left ventricle. No modifications in atrial NP gene expression were observed in either control or 2K-1C animals. ET(A) blockade decreased BNP circulating levels but did not affect ANF plasma levels in clipped rats. ABT-627 increased alpha-myosin heavy chain gene expression and decreased the abundance of the beta isoform transcript.. The results obtained in the present investigation show the participation of ET-1 in the increased expression of ventricular NP in 2K-1C renovascular hypertension and an apparent lack of effect of ET(A) blockade on atrial NP gene expression in both control and hypertensive animals thus showing that in vivo, atrial and ventricular NP gene expression are differentially regulated.

Topics: Analysis of Variance; Animals; Atrasentan; Atrial Natriuretic Factor; Blotting, Northern; Collagen; Endothelin Receptor Antagonists; Endothelin-1; Gene Expression Regulation; Heart Atria; Heart Ventricles; Hypertension, Renovascular; Male; Natriuretic Peptide, Brain; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; RNA, Messenger

Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of properties of HO and its products, we hypothesized that HO would be important for the regulation of blood pressure and ischemic injury. We studied chronic renovascular hypertension in mice deficient in the inducible isoform of HO (HO-1) using a one kidney-one clip (1K1C) model of disease. Systolic blood pressure was not different between wild-type (HO-1(+/+)), heterozygous (HO-1(+/-)), and homozygous null (HO-1(-/-)) mice at baseline. After 1K1C surgery, HO-1(+/+) mice developed hypertension (140+/-2 mm Hg) and cardiac hypertrophy (cardiac weight index of 5.0+/-0.2 mg/g) compared with sham-operated HO-1(+/+) mice (108+/-5 mm Hg and 4.1+/-0.1 mg/g, respectively). However, 1K1C produced more severe hypertension (164+/-2 mm Hg) and cardiac hypertrophy (6.9+/-0.6 mg/g) in HO-1(-/-) mice. HO-1(-/-) mice also experienced a high rate of death (56%) within 72 hours after 1K1C surgery compared with HO-1(+/+) (25%) and HO-1(+/-) (28%) mice. Assessment of renal function showed a significantly higher plasma creatinine in HO-1(-/-) mice compared with HO-1(+/-) mice. Histological analysis of kidneys from 1K1C HO-1(-/-) mice revealed extensive ischemic injury at the corticomedullary junction, whereas kidneys from sham HO-1(-/-) and 1K1C HO-1(+/-) mice appeared normal. Taken together, these data suggest that chronic deficiency of HO-1 does not alter basal blood pressure; however, in the 1K1C model an absence of HO-1 leads to more severe renovascular hypertension and cardiac hypertrophy. Moreover, renal artery clipping leads to an acute increase in ischemic damage and death in the absence of HO-1.

Topics: Acute Kidney Injury; Animals; Blood Pressure; Cardiomegaly; Chronic Disease; Creatinine; Disease Models, Animal; Endothelin Receptor Antagonists; Endothelin-1; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Heterozygote; Homozygote; Hypertension, Renovascular; Immunohistochemistry; Kidney; Membrane Proteins; Mice; Mice, Knockout; Nephrectomy; Organ Size; Receptor, Endothelin A; Renal Artery Obstruction; RNA, Messenger; Severity of Illness Index; Survival Rate

Prognosis in Takayasu's arteritis is limited owing to renovascular hypertension. The authors report a patient with Takayasu's arteritis who had been unilaterally nephrectomized and presented with malignant hypertension due to renal artery stenosis. Hypertension was refractory to conventional antihypertensive treatment, and stenosis was not accessible by interventional angioplasty. Initiation of enalapril and losartan therapy was successful in improving blood pressure without deterioration of renal function due to ischemic failure. Antihypertensive treatment resulted in dramatically stimulated endogenous nitric oxide (NO) synthesis, while elevated plasma endothelin-1 levels were unchanged. Renovascular hypertension in Takayasu's arteritis is associated with an imbalance of vasoconstrictor peptide endothelin-1 and vasodilator peptide NO. Successful treatment of hypertension by enalapril or losartan results in improved endogenous NO synthesis, which putatively counterbalances excessive vasoconstrictor actions and may retard the progression of renal failure.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Enalapril; Endothelin-1; Female; Humans; Hypertension, Renovascular; Losartan; Middle Aged; Nephrectomy; Nitric Oxide; Prognosis; Renal Artery Obstruction; Takayasu Arteritis; Vasoconstrictor Agents; Vasodilator Agents

There is still considerable uncertainty regarding sensitivity of arterial blood pressure to endogenous peptides in renal hypertension. Many pathological processes including hypertension have been shown to be associated with release of endothelin-1 (ET-1). However the role of ET-1 in regulation of arterial blood pressure in hypertension is still controversial.. The role of endothelin-1 (ET-1) and angiotensin-II (AT-II) in malignant phase of renovascular hypertension has been assessed on the basis of arterial blood pressure increase and ETA receptor density measurements in Glodblatt-hypertensive rats (RVH).. The arterial blood pressure response to sympatomimetic amines, vasopressors, the plasma ET-1 and AT-II levels as well as renal subtype-ETA receptor density were significantly increased in RVH rats with malignant hypertension. The dominance of vasopressor ETA receptors in RVH rats suggest the contribution of endothelin peptides to malignant renovascular hypertension. (Tab. 1, Fig. 7, Ref. 25.)

Topics: Acetylcholine; Angiotensin II; Animals; Blood Pressure; Endothelin-1; Hypertension, Renovascular; Male; Norepinephrine; Rats; Rats, Wistar; Sympathomimetics; Vasoconstrictor Agents; Vasodilator Agents

Nonsteroidal anti-inflammatory drugs have been reported to exacerbate hypertension. In this study, we tested the hypothesis that a nitric oxide-releasing derivative of naproxen would ameliorate hypertension in the rat. Hypertension was induced by partially occluding one renal artery (the "2K,1C" model), and 2 wk later the rats started receiving naproxen, the nitric oxide-releasing derivative HCT-3012, or vehicle each day for 2 wk. Naproxen significantly exacerbated the hypertension. HCT-3012 significantly reduced blood pressure relative to both the naproxen- and vehicle-treated groups. Both naproxen and HCT-3012 markedly suppressed whole blood thromboxane B(2) synthesis. In studies of anesthetized rats, naproxen significantly enhanced the late hypertensive response to endothelin-1 and significantly blunted the early hypotensive response. In contrast, HCT-3102 did not affect either response to endothelin-1. In vitro, HCT-3012 significantly reduced the responsiveness of aortic rings to the contractile effects of phenylephrine. These studies suggest that HCT-3012 reduces blood pressure in hypertensive rats, not simply through the vasodilatory actions of the nitric oxide it releases, but through alterations in the responsiveness of the vasculature to endogenous pressor agents.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Endothelin-1; Hypertension, Renovascular; In Vitro Techniques; Isometric Contraction; Male; Muscle, Smooth, Vascular; Naproxen; Nitrates; Nitric Oxide Donors; Nitrites; Nitroglycerin; Nitroprusside; Phenylephrine; Rats; Rats, Wistar; Renal Artery; Thromboxane B2

Renovascular hypertension in the two-kidney, one clip (2K1C) model is characterized by initially elevated angiotensin-II (A-II) plasma concentrations, caused by ischemia in the clipped kidney and shear stress in the nonclipped kidney. These features are known stimuli of the endothelin (ET) system. The aim of this study was to analyze whether the renal ET system is activated in 2K1C renal hypertension in the rat. Wistar Kyoto rats (9 weeks old) were randomly assigned to four groups. Groups 1 and 3 underwent renal artery clipping, groups 2 and 4 were sham-operated. Groups 1 and 2 were used for analysis at 10 days after clipping, groups 3 and 4 12 weeks after clipping. We measured immunoreactive ET-1 renal tissue concentration as well as the ET(A)- and ET(B)-receptor density and affinity in renal cortex and medulla. We detected an increased immunoreactive ET-1 tissue concentration compared to the sham-operated control in the renal cortex of the nonclipped kidney 10 days (25.6 +/- 12.0 pg/g vs 12.5 +/- 5.0, 1 pg/g; p < 0.05) and in the renal cortex of the clipped kidney 90 days after clipping (92.4 +/- 47 pg/g vs 22.9 +/- 21 pg/g; p < 0.05), An increased ET(A)-receptor density was revealed in the renal medulla of the clipped kidney 10 days (624 +/- 130 fmol/mg vs 276 +/- 68 fmol/mg; p < 0.05) and 90 days (859 +/- 131 fmol/mg vs 493 +/- 93 fmol/mg; p < 0.05) after clipping. There were no differences in ET(B)-receptor density or binding affinity of either ET(A)- or ET(B)-receptors. In the 2K1C rat model of renovascular hypertension the renal ET system is activated. This activation is time-dependent and also dependent on the specific pathophysiological condition (clipped vs nonclipped). Increased ET-1 tissue concentration and upregulation of ET(A)-receptor density might lead to a synergistic activation of the ET system.

Topics: Animals; Endothelin-1; Hypertension, Renovascular; Kidney; Rats; Rats, Inbred WKY; Receptor, Endothelin A; Receptor, Endothelin B; Receptors, Endothelin

To investigate the antihypertensive effects of D-polymannuronic sulfate (DPS), a kind of sulfated polysaccharide, and the underlying mechanisms in renovascular hypertensive rats (RHR).. Used two-kidney one clip (Goldblatt, 2-K 1C) method to produce RHR model. DPS was given i.v. or ig for 5 wk with the initiation of establishment of RHR. Serum nitric oxide (NO) was determined with NO kit; plasma angiotensin II (Ang II) and endothelin-1 (ET-1) were measured by radioimmumoassays.. In acute therapeutic experiments, DPS markedly reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) dose-dependently and decreased heart rate (HR) with reduction in arterial blood pressure. In the prophylactic experiments, DPS prevented the rise in SBP and DBP in a dose-dependent manner. The hypotensive potency of DPS 50 mg/kg is comparable to that of captopril (14 mg/kg). Moreover, DPS elevated serum NO contents and lowered plasma concentrations of Ang II and ET-1.. The antihypertensive activities of DPS might be involved both in increasing the generation of nitric oxide and in decreasing the production of angiotensin II and endothelin-1 in vivo.

Topics: Angiotensin II; Animals; Antihypertensive Agents; Blood Pressure; Endothelin-1; Heart Rate; Hexuronic Acids; Hypertension, Renovascular; Male; Nitric Oxide; Phaeophyceae; Rats; Rats, Inbred WKY

The cardiac abnormalities associated with hypertension include left ventricular hypertrophy and vascular changes. The latter may affect the cardiac microvasculature and predispose to myocardial ischemia. To test the hypothesis that endothelin-1 contributes to changes in the microcirculation of the heart, we studied cardiac microvessels of the deoxycorticosterone acetate-salt (DOCA-salt) model of hypertension in the rat, in which the endothelin system is activated, and the effect of the endothelin-A (ET(A)) subtype-selective endothelin receptor antagonist A-127722. A-127722 (30 mg x kg(-1) x d(-1)) was administered for 4 weeks. Arterioles (

Topics: Animals; Atrasentan; Coronary Circulation; Coronary Vessels; Desoxycorticosterone; Endothelin Receptor Antagonists; Endothelin-1; Heart; Hypertension, Renovascular; Male; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptors, Endothelin; Sodium Chloride, Dietary

Spontaneously hypertensive rats (SHR), renovascular hypertensive rats [two-kidney one clip Goldblatt (2-K 1C) and 1-K 1C], and SHR treated with the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), do not respond to endothelin (ET) receptor antagonists with a decrease in blood pressure. However, treatment with ET receptor antagonists has shown some beneficial renal and coronary effects in SHR. In this study we examined tissues from SHR, L-NAME-treated SHR, 2-K 1C, and 1-K 1C, using in situ hybridization with a specific rat preproET-1 cRNA probe to evaluate preproET-1 mRNA abundance in blood vessels, heart, and kidneys. Grain density was similar in SHR and Wistar-Kyoto (WKY) rats in all tissues examined. L-NAME-treated SHR showed increased grain density vs. SHR in endothelium of aorta and of small coronary arteries and in kidney glomeruli, but not in renal or mesenteric arteries. 2-K 1C presented increased grain density in coronary arteries and in glomeruli of the unclipped but not the clipped kidney vs. glomeruli of control rats. 1-K 1C rats exhibited increases in preproET-1 mRNA relative to unilaterally nephrectomized control rats in endothelium of aorta and in mesenteric and coronary arteries, but not in renal arteries or glomeruli. None of the hypertensive models studied showed detectable evidence of myocardial overexpression of preproET-1 mRNA. Therefore, tissue-specific enhancement of ET-1 expression may underlie ET-dependent functional alterations and may explain the beneficial effects of ET receptor antagonists in the coronary circulation or in the kidney in some hypertensive models, but not in SHR.

Topics: Animals; Blood Vessels; Endothelin-1; Endothelins; Enzyme Inhibitors; Gene Expression Regulation; Hypertension; Hypertension, Renovascular; In Situ Hybridization; Kidney; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Protein Precursors; Rats; Rats, Inbred SHR; Rats, Inbred WKY

To evaluate whether the cumulative hypotensive effect of the endothelin-1 receptor antagonist bosentan, previously demonstrated in the presence of an angiotensin converting enzyme inhibitor, persists under angiotensin II receptor blockade with losartan.. The model of hypertension was canine renovascular hypertension (Page hypertension).. Ten conscious dogs, studied on two occasions, were administered losartan (a 0.1 mg/kg bolus plus 90 min infusion at 0.1 mg/kg per min) and then bosentan vehicle (experiment I) or losartan and then two cumulative doses of bosentan (a 0.3 mg/kg bolus plus 30 min infusion at 0.7 mg/kg per min; and a 3 mg/kg bolus plus 30 min infusion at 7 mg/kg per min; experiment II).. At the end of the study, mean aortic pressure in dogs had decreased by 14% in experiment I (from 139 +/- 4.7 to 119 +/- 4.7 mmHg, P<0.05), whereas a 28% reduction occurred in experiment II (from 145 +/- 8.9 to 104 +/- 5.0 mmHg, P<0.005), corresponding to an additional 14% decrease after administration of bosentan (P<0.005 between groups). This cumulative effect of bosentan was related to a decrease in systemic vascular resistance (from 1220 +/- 119 to 847 +/- 189 mmHg/ml per min per kg x 10(3), P<0.05). Plasma angiotensin II level increased similarly in both experiments (in experiment I from 133 +/- 43 to 622 +/- 145 pg/ml, P=0.01; in experiment II from 198 +/- 63 to 771 +/- 134 pg/ml, P<0.005) whereas plasma endothelin-1 level increased only in experiment II (from 3.8 +/- 0.4 to 32.7 +/- 3.2 pg/ml, P<0.001).. The cumulative hypotensive effect of bosentan suggests that, besides angiotensin II, endothelin-1 is independently involved in the pathophysiology of hypertension, which presents new therapeutic perspectives.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Animals; Blood Pressure; Bosentan; Disease Models, Animal; Dogs; Endothelin Receptor Antagonists; Endothelin-1; Hypertension, Renovascular; Infusions, Intravenous; Losartan; Radioimmunoassay; Receptor, Endothelin A; Sulfonamides; Vascular Resistance

The present study was performed to compare circulating levels of tumour necrosis factor-alpha (TNFalpha) and plasma endothelin 1 (ET-1), of hypertensive patients with or without renal failure and with those of normotensive healthy subjects. The study population consisted of 21 healthy normotensive subjects and 22 hypertensive patients, 11 with essential hypertension, and 11 with hypertension and chronic renal failure (CRF). Plasma ET-1 levels, serum TNFalpha and creatinine, creatinine clearance, 24-h urinary albumin excretion (UAE) were assayed, and 24-h blood pressure monitoring was obtained in all subjects. Office blood pressure was similar between hypertensive patients with and without CRF. However, 24-h blood pressure was greater in patients with CRF than in those with essential hypertension and normal renal function. Patients with hypertension manifested greater ET-1 levels than normotensive subjects (P < 0.01). Serum TNFalpha and ET-1 levels were higher in hypertensive patients with CRF than in patients with essential hypertension and normotensive subjects. In the 22 hypertensive patients, TNFalpha levels were negatively correlated with serum creatinine (r=0.60; P < 0.01), and ET-1 levels were positively correlated with UAE (r=0.47, P < 0.05). The present study has shown that hypertensive patients, and particularly those with renal insufficiency, manifest abnormal blood levels of ET-1 and TNFalpha. These factors could contribute to both cardiovascular and renal damage.

Topics: Adult; Albuminuria; Blood Pressure Monitoring, Ambulatory; Creatinine; Endothelin-1; Female; Humans; Hypertension; Hypertension, Renovascular; Kidney Failure, Chronic; Male; Middle Aged; Tumor Necrosis Factor-alpha

The ultrastructural localization of immunoreactivity to nitric oxide synthase (type-III and type-II) and endothelin-1 was examined by using pre-embedding peroxidase-antiperoxidase techniques in the coronary and cerebral basilar arteries in renal hypertensive rats. Renal hypertension was produced by excision of the right kidney and clipping of the left renal artery. Controls were normotensive sham-operated rats (right surgical nephrectomy; a clip inserted near the left renal artery). Both in controls and hypertensive rats, immunoreactivities for nitric oxide synthase-III and endothelin-1 were localized within subpopulations of endothelial cells. In addition, signs of translocation of nitric oxide synthase-III were noted from the cytoplasm to the Golgi complex in endothelial cells of the basilar artery of hypertensive animals. Neither controls nor hypertensive rats showed immunoreactivity for nitric oxide synthase-II. Preparations of the right coronary artery from hypertensive rats displayed fewer endothelial cells positive to nitric oxide synthase-III than in controls, although there were no significant changes in the distribution of endothelin-1-positive endothelial cells in the coronary artery of hypertensive rats. In contrast, the basilar artery from hypertensive rats displayed no changes in the percentage of endothelial cells immuno-positive either for nitric oxide synthase-III or for endothelin-1. In consequence, the ratio of nitric oxide synthase-III:endothelin-1 was reduced in the coronary but not in the basilar artery. Therefore, the nitric oxide/endothelin-1 system appears to play different roles in the coronary and cerebral circulations during renal hypertension.

Topics: Animals; Basilar Artery; Coronary Vessels; Endothelin-1; Endothelium, Vascular; Hypertension, Renovascular; Male; Microscopy, Immunoelectron; Nitric Oxide Synthase; Rats; Rats, Sprague-Dawley; Reference Values; Renal Artery

To examine the value of plasma endothelin-1 (ET-1), we measured the level of plasma ET-1 activity of peripheral venous blood and selective renal venous blood in renovascular hypertension patients, and compared that activity with corresponding renin activity and split renal function.. ET-1 level, renin activity in selective renal venous blood and peripheral venous blood, and 99mTc-dimercaptosuccinic acid renal uptake as a split renal function test were measured in 11 patients (mean 42.1 years old) with renovascular hypertension (RVH) and 6 patients with both renal cell cancer (RCC) and essential hypertension.. 1. In patients with RVH, resting peripheral venous plasma ET-1 ranged from 0.6 to 8.1 (mean 4.07) pg/ml and was higher than the normal level (p <0.01). However, the renal vein ET-1 ratio was nor correlated with the renal vein renin ratio. 2. In patients with RCC, resting peripheral venous plasma ET-1 was not different from the normal level. There was no step-up of plasma ET-1, or renin among renal veins, or the proximal and distal parts of the interior vena cava. 3. Both renal vein renin ratio and renal vein ET-1 ratios were inversely correlated with t99mTC-dimercaptosuccinic acid renal uptake as a split renal function examination in patients with RVH. 4. The peripheral plasma ET-1 level was correlated with the degree of stenosis of the renal artery in patients with RVH of a unilateral lesion, but not bilateral lesions.. These results suggest that ET-1 may take part in the hypertensive mechanisms of RVH in addition to the renin-angiotensin system, but its significance in RVH still remains to be examined.

Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Captopril; Child, Preschool; Endothelin-1; Female; Humans; Hypertension, Renovascular; Kidney; Male; Middle Aged; Organotechnetium Compounds; Radioimmunoassay; Radionuclide Imaging; Renal Artery; Renin; Succimer; Technetium Tc 99m Dimercaptosuccinic Acid

Renal effects of FR139317, an endothelin ETA receptor antagonist, were examined using anesthetized normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The intravenous bolus injection of FR139317 (10 mg/kg) produced a slight decrease in mean blood pressure (MAP; -13%) in the control rats and this hypotension was accompanied by a moderate renal vasodilation (renal vascular resistance: RVR; -12%). In the DOCA-salt hypertensive rat, FR139317 had a more pronounced hypotensive effect (MAP; -26%) accompanied by a potent renal vasodilation (RVR; -33%). FR139317 significantly increased renal blood flow only in the DOCA-salt rats. In contrast, FR139317 produced a significant decrease in urine flow and urinary sodium excretion only in control rats. Northern blot analysis revealed that the renal prepro endothelin-1 (ET-1) mRNA level was significantly increased in DOCA-salt hypertensive rats. Thus, it seems likely that endogenous ET-1 is responsible for the maintenance of DOCA-salt-induced hypertension. We also suggest that at least in part, ET-1 and ETA receptors are involved in renal hemodynamic abnormalities in DOCA-salt-induced hypertension. The augmentation of renal ET-1 production may possibly have a function in the development and maintenance of DOCA-salt-induced hypertension.

Topics: Animals; Azepines; Blood Pressure; Blotting, Northern; Body Weight; Desoxycorticosterone; Endothelin Receptor Antagonists; Endothelin-1; Endothelins; Hypertension, Renovascular; Indoles; Kidney; Male; Organ Size; Protein Precursors; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptors, Endothelin; Renal Circulation; RNA, Messenger

To investigate a model of experimental hypertension that exhibits severe hypertrophy of small blood vessels but in which deoxycorticosterone acetate (DOCA) and salt are absent: the one-kidney, one clip model of Goldblatt renovascular hypertension, which is non-renin-dependent, and compare it with the renin-dependent two-kidney, one clip Goldblatt hypertensive rat, in which additionally vascular hypertrophy is less severe.. Endothelin-1 gene expression in blood vessels and in the heart was examined by Northern blot analysis.. After 2 or 4 weeks of application of the silver clip to unilaterally nephrectomized rats, the aorta and mesenteric arteries exhibited a significant increase in the intensity of the 2.3 kb band corresponding to hybridization with endothelin-1 messenger RNA (mRNA) in comparison with results obtained in control unilaterally nephrectomized rats. No increase was noted in the blood vessels of the two-kidney, one clip hypertensive rat at 2 or 4 weeks, but significant increases were found at 8 weeks in aorta, but not in mesenteric arteries. Cardiac abundance of endothelin-1 mRNA was also increased in ventricles and in the left atria of one-kidney, one clip hypertensive rats, but only in the late phase (at 8 weeks) in two-kidney, one clip hypertensive rats.. Because one-kidney, one clip hypertensive rats presented severe vascular hypertrophy whereas two-kidney, one clip hypertensive rats only did so in the late phase of hypertension, these results lend further support to there being a relationship between vascular hypertrophy and endothelin-1 vascular overexpression in experimental models of hypertension. They also demonstrate that enhancement of the expression of endothelin-1 gene in blood vessels and in the heart of hypertensive rats may occur in the absence of exposure to DOCA and salt, and that endothelin-1 gene overexpression in experimental hypertension occurs early in non-renin-dependent, volume-expanded models such as the one-kidney, one clip or the DOCA-salt hypertensive rat, but only in the progressively non-renin-dependent late phase of the initially renin-dependent volume-contracted two-kidney, one clip hypertensive rat.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Disease Models, Animal; Endothelin-1; Endothelium, Vascular; Heart Rate; Hypertension, Renovascular; Kidney; Mesenteric Arteries; Models, Cardiovascular; Rats; Rats, Sprague-Dawley; Renin; RNA, Messenger; Severity of Illness Index; Time Factors