UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of the present study was to examine the viscoelastic properties of the carotid artery in genetically identical rats exposed to similar levels of blood pressure sustained by different mechanisms. Eight-week old male Wistar rats were examined 2 weeks after renal artery clipping (two-kidney, one clip [2K1C] Goldblatt rats, n = 53) or sham operation (n = 49). One half of the 2K1C and sham rats received the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 1.48 mmol/L) in their drinking water for 2 weeks after the surgical procedure. Mean blood pressure increased significantly in the 2K1C-water (182 mm Hg), 2K1C-L-NAME (197 mm Hg), and sham-L-NAME (170 mm Hg) rats compared with the sham-water rats (127 mm Hg). Plasma renin activity was not altered by L-NAME but significantly enhanced after renal artery clipping. A significant and similar increase in the cross-sectional area of the carotid artery was observed in L-NAME and vehicle-treated 2K1C rats. L-NAME per se did not modify cross-sectional area in the sham rats. There was a significant upward shift of the distensibility-pressure curve in the L-NAME- and vehicle-treated 2K1C rats compared with the sham-L-NAME rats. L-NAME treatment did not alter the distensibility-pressure curve in the 2K1C rats. These results demonstrate that the mechanisms responsible for artery wall hypertrophy in renovascular hypertension are accompanied by an increase in arterial distensibility that is not dependent on the synthesis of nitric oxide.
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PMID:Chronic nitric oxide synthase inhibition and carotid artery distensibility in renal hypertensive rats. 754 53

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.
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PMID:Endothelin-1 gene expression in blood vessels and kidney of spontaneously hypertensive rats (SHR), L-NAME-treated SHR, and renovascular hypertensive rats. 959 89

Surgical correction of renal artery stenosis in Goldblatt hypertension rapidly normalizes blood pressure and increases renal function. This study was conducted in 1-kidney, 1 clip (1K1C) Goldblatt hypertensive rats to examine whether the unclipping-induced reversal of blood pressure and renal function is mediated by nitric oxide (NO). The 1K1C rats were prepared and given tap water with or without supplementation of NG-nitro-L-arginine methyl ester (L-NAME). Systolic blood pressure (SBP) before and after renal artery clipping was measured with the tail-cuff method. Four weeks later, surgical unclipping was performed while blood pressure and renal function responses were determined. The results show that clipping the renal artery for 4 weeks increased SBP from 140+/-5 to 183+/-6 mm Hg (P<0.05). Concurrent L-NAME treatment accelerated and aggravated the clipping-induced increases in SBP from 138+/-6 to 219+/-8 mm Hg (P<0.05). Surgical unclipping reduced blood pressure to normotensive levels within 2 hours in all hypertensive rats with and without chronic or acute L-NAME treatment. However, the magnitude of reductions in blood pressure in the initial 1 hour after unclipping was significantly less in L-NAME-treated rats than in nontreated rats (9+/-2% versus 16+/-1%, P<0.05). Despite reducing blood pressure, unclipping significantly increased glomerular filtration rate, urine flow, and sodium and potassium excretions, but the extent of the increases in these renal functions was significantly attenuated in L-NAME-treated rats. These data suggest that NO production partly contributes to the hypotensive and renal responses to unclipping but does not mediate the reversal of renovascular hypertension of this model.
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PMID:Nitric oxide synthesis inhibition retards surgical reversal of one-kidney Goldblatt hypertension in rats. 974 Jun 22

Endothelins (ET) are 21-aminoacid peptides produced ubiquitously, which were discovered originally as endothelial products. These peptides may play important roles in cardiovascular physiology and pathophysiology. As the pathophysiologic roles of endothelins in cardiovascular disease become increasingly apparent, the potential therapeutic use of endothelin antagonists or endothelin converting enzyme inhibitors is recognized. The main endothelin produced by the endothelium is ET-1. Endothelin-1 is overexpressed in the vascular wall of salt-dependent models of hypertension, such as DOCA-salt hypertensive rats, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, and in stroke-prone SHR, angiotensin II-infused rats and 1-kidney 1 clip Goldblatt hypertensive rats, but not in SHR, 2-K 1C hypertensive rats or L-NAME-treated rats. The vasoconstrictor effect of ET-1 may contribute to blood pressure elevation and its growth-promoting action to vascular hypertrophy in the hypertensive models which overexpress ET-1 in blood vessels. In rats without generalized activation of the endothelin system, expression of ET-1 is often enhanced in coronary arteries, which suggests a role for ET-1 in myocardial ischemia in hypertension. In rats overexpressing ET-1, ETA/B and ETA-selective antagonists lowered blood pressure slightly, and significantly reduced vascular growth, particularly of small arteries, suggesting that ET-1 has a direct effect on growth. Protection from renal injury and from stroke has also been demonstrated in hypertensive rats treated with endothelin antagonists. In normotensive human subjects endothelin-dependent tone can be shown in the forearm. In a study of mild hypertensive patients, the ETA/B antagonist bosentan reduced blood pressure similarly to an ACE inhibitor. Moderate to severe hypertensive patients presented enhanced expression of ET-1 mRNA in the endothelium of subcutaneous resistance arteries. In blacks with familial hypertension increased plasma levels of endothelin have been found. Thus, ET-1 may play a role in some experimental hypertensive models and in human hypertension. In summary, endothelial ET-1 may be overexpressed in the more severe forms of hypertension, and in certain special populations which may respond particularly well to endothelin antagonism. Endothelin antagonists may prove to be effective disease-modifying agents if in future clinical trials they are shown clinically to blunt vascular growth and endothelial dysfunction, reduce stroke and exert the cardioprotective and renal protective effects already reported in experimental hypertension. These agents could contribute to reduce the long-term complications of hypertension, which remains to be demonstrated in humans.
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PMID:Endothelin: role in hypertension. 983 May 7

The endothelins (ET) are potent 21-amino-acid vasoconstrictor peptides produced in many different tissues, particularly in the endothelium of blood vessels. ET-1 is the main endothelin secreted by the endothelium, and acts in a paracrine or autocrine fashion on blood vessels by interacting with ETA or ETB receptors on smooth muscle to stimulate contraction or on ETB receptors on endothelial cells to induce the release of vasorelaxants (nitric oxide and prostacyclin). Production of ET-1 is enhanced in several experimental models of hypertension in the rat, such as sodium-sensitive forms, e.g. deoxycorticosterone acetate (DOCA)-salt hypertensive, DOCA-salt-treated spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats, as well as other models such as stroke-prone SHR, angiotensin II-infused rats and fructose-fed rats, and possibly 1-K 1C Goldblatt hypertensive rats. In contrast, SHR, 2-K 1C Goldblatt hypertensive rats and nitric oxide-deficient (L-NAME-treated) hypertensive rats do not exhibit an ET-1 component. Endothelin dependency is manifested by excessive vascular growth, particularly in small arteries, and blood pressure lowering and regression of vascular growth after treatment with endothelin antagonists. The latter may be combined ETA/ETB or selective ETA antagonists, of which several are orally active and already in clinical development. In humans, endothelin-dependent vascular tone has been shown in studies of forearm blood flow. Enhanced expression of ET-1 mRNA has been demonstrated in the endothelium of small arteries of patients with moderate to severe hypertension. In a 4-week trial the combined ETA/ETB antagonist bosentan reduced the blood pressure of essential hypertensive patients equally to enalapril. Bosentan improved hemodynamics in patients with heart failure in acute and 2-week-long studies. Endothelin antagonists also offer promise in a rapidly fatal condition, primary pulmonary hypertension. Thus, the endothelin system appears to be involved in different forms of cardiovascular disease in experimental animals and humans, and its interruption offers great promise as a new therapeutic intervention in hypertension, heart failure and other diseases.
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PMID:Endothelin and endothelin antagonists in hypertension. 988 74

Endothelin-1 (ET-1) is overexpressed in the vascular wall in certain models of experimental hypertension: deoxycorticosterone acetate salt-treated rats, deoxycorticosterone acetate salt-treated spontaneously hypertensive rats (SHR), stroke-prone SHR, Dahl salt-sensitive rats, angiotensin II-infused rats, and 1-kidney 1 clip Goldblatt rats; it is not overexpressed in SHR, 2-kidney 1-clip hypertensive rats, or L-NAME-treated rats. In hypertensive rats without generalized vascular overexpression, however, expression of ET-1 was often enhanced in intramyocardial coronary arteries, suggesting a role of endothelin in myocardial ischemia in hypertension. In rats overexpressing ET-1, ET(A/B) and ET(A)-selective receptor antagonists lowered blood pressure and reduced vascular growth, particularly in small arteries, beyond what could be attributed to blood pressure lowering, suggesting a direct effect of ET-1 on growth. Hypertensive rats treated with endothelin antagonists are protected from stroke and renal injury. The ET(A/B) antagonist bosentan induced blood-pressure reductions in mildly hypertensive patients similar to those achieved with an angiotensin-converting enzyme inhibitor. Moderately to severely hypertensive patients presented with enhanced expression of prepro-ET-1 mRNA in the endothelium of subcutaneous resistance arteries, suggesting that these stages of hypertension may respond particularly well to endothelin antagonism. Hypertensive patients with coronary artery disease have increased arterial expression of ET-1, and increased plasma levels of immunoreactive endothelin have been described in black patients. ET-1 plays an important role in atherosclerosis, for which hypertension is an important risk factor. Thus, ET-1 may be involved in experimental and human hypertension. Endothelin antagonists may prove effective as disease-modifying agents if they are shown clinically, as they are experimentally, to offer target organ protection and reduce long-term complications of hypertension. This remains to be demonstrated in humans.
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PMID:State-of-the-Art lecture. Role of endothelin-1 in hypertension. 1052 77

The role of endothelins (ET) in blood pressure elevation remains controversial. Data supporting involvement of the ET system in different forms of genetic and experimental hypertension in the rat has appeared in the literature in recent years. Production of endothelin (ET)-1 may be enhanced in several experimental rat models of hypertension. Examples of these exhibiting increased preproendothelin-1 mRNA or peptide in the vasculature include salt-sensitive forms like deoxycorticosterone (DOCA)-salt hypertension, DOCA-salt treated spontaneously hypertensive rat (SHR) and Dahl salt-sensitive rats, and other models like stroke-prone SHR, angiotensin II-infused rats and fructose-fed rats, and possibly 1-kidney 1 clip (1-K 1C) Goldblatt hypertensive rats. SHR, 2-kidney 1 clip (2-K 1C) Goldblatt hypertensive rats and chronic N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated hypertensive rats do not appear to exhibit an ET-1 component. Significant vascular growth, and a hypotensive response and regression of vascular growth after treatment with an ET antagonist demonstrate the endothelin-dependency present in some hypertensive models. Severity of high blood pressure elevation, salt-sensitivity and insulin resistance may be common denominators of involvement of the ET system in hypertension. ET antagonism in hypertension may result in regression of vascular damage, prevention of stroke and renal failure and improvement of heart failure. Whether the same is true in human hypertension remains to be established.
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PMID:Endothelin: role in experimental hypertension. 1097 78

The aim of this study was to examine the effects of L-arginine, a nitric oxide (NO) precursor, on protein expression of endothelial nitric oxide (eNOS), nitrite/nitrate content, protein expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) and the activity of mitogen-activated protein kinase (MAPK) in cardiac tissues in renovascular hypertensive rats (RHR). The Goldblatt renovascular hypertensive model was established by two-kidney one clip method. The rats were divided into four groups, respectively treated with 50, 150 and 450 mg/kg L-arginine and 150 mg/kg L-arginine plus 10 mg/kg L-NAME (an eNOS inhibitor) (i.p.). Another group did not receive specific treatment from the 5th week after renal artery constriction. Control group was sham-operated. Mean arterial blood pressure (MABP) and the ratio of left ventricular weight to body weight (LVW/BW) were measured 8 weeks after treatment. eNOS protein expression, nitrite/nitrate content, MKP-1 protein expression and MAPK activity in cardiac tissues were detected using Western blot analysis, enzyme-reduction method and substrate in-gel kinase assay, respectively. It was found that L-arginine significantly inhibited the increase of MABP and LVW/BW, attenuated the activity of MAPK, increased protein expression of eNOS and MKP-1 and potentiated production of NO in cardiac tissue with the most effective dosage of 150 mg/kg, and these effects of L-arginine could be inhibited by L-NAME. These results suggest that MKP-1 may play an important role in the NO-induced inhibition of myocardial hypertrophy. The anti-hypertrophic effects of L-arginine may involve increase of eNOS protein expression and NO production, potentiation of MKP-1 protein expression, and inhibition of MAPK activity in the cardiac tissue of RHR.
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PMID:[Role of mitogen-activated protein kinase in the inhibition of myocardial hypertrophy by nitric oxide in renovascular hypertensive rats]. 1135 94

The change of blood pressure and heart rate after intravenous injection of Korea red ginseng (KRG) were studied in the conscious normotensive and one-kidney, one-clip Goldblatt hypertensive (1K, 1C-GBH) rats. Crude saponin (CS) of KRG (50, 100 mg/kg i.v.) induced a hypotensive effect and bradycardia in a dose-dependent manner in the anesthetized rats. On the other hand, CS of KRG (100 mg/kg) induced a hypotensive effect and reflex tachycardia in the conscious rats. Saponin-free fraction (SFF) of KRG did not affect them in the anesthetized normotensive rats (P>.05). The maximal hypotensive effect by CS of KRG in the conscious 1K, 1C-GBH hypertensive rats and L-nitroarginine methyl ester (L-NAME, 40 mg/kg)-treated conscious hypertensive rats was not different from that of conscious normotensive rats (Delta 31.6+/-6.3, Delta 27.5+/-5.8 vs. Delta 26.7+/-4.3 mmHg, P>.05). However, pretreatment of L-NAME significantly inhibited the reflex tachycardia by CS of KRG (70.8+/-7.0 vs. 30.6+/-15.0 bpm, P<.05). Hemolysate-sensitive nitric oxide (NO) current by the CS of KRG was greater than that of the SFF of KRG (651.9+/-128.2 pA for CS and 164.9+/-92.5 pA for SFF, P<.001). These findings suggest that KRG has a hypotensive effect and its effect may be due to saponin fraction of KRG in the conscious rats. The releasing effect of NO of KRG, like NO donor, may be partly contributed to the hypotensive effect of KRG.
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PMID:Effect of Korea red ginseng on the blood pressure in conscious hypertensive rats. 1174 35

The blood pressure lowering effect of a fruit and vegetable-rich diet is a necessary dietary lifestyle measure now included the guidelines for the management of arterial hypertension. Furthermore, flavonoids represent a major class of plant polyphenolics. The present review addresses the antihypertensive effect of quercetin, one of the most abundant flavonoids present in fruits and vegetables, and probably the best studied flavonoid because of its high biological activity. Quercetin has been shown to induce a progressive, dose-dependent and sustained reduction in blood pressure when given chronically in several rat models of hypertension, including spontaneously hypertensive rats, L-NAME-treated rats, DOCA-salt hypertensive rats, two-kidney one-clip Goldblatt rats, rats with aortic constriction and Dahl salt-sensitive hypertensive rats. Quercetin was also effective in reducing blood pressure in rat models of metabolic syndrome, including the obese Zucker rats as well as rats treated with a high-sucrose, high-fat diet. Quercetin also prevented morphological and functional changes in the heart, vessels and kidney, while increasing production of reactive oxygen species associated with hypertension. A high dose of quercetin also reduced blood pressure in stage 1 hypertensive patients in a randomized, double-blind, placebo-controlled, crossover study. Since raised blood pressure is the major cause of stroke as well as an important risk factor for ischemic heart disease, we propose that the blood pressure-lowering effect of quercetin could be an important mechanism contributing to the reduced risk of myocardial infarction and stroke observed with fruit and vegetables-rich diets, and possibly with flavonoid-rich diets.
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PMID:Antihypertensive effects of the flavonoid quercetin. 1930 94

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