Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to examine the influence of the endothelium on the extracellular magnesium induced relaxation of basal tension in isolated aortas from both mineralocorticoid-salt (DOCA-salt) hypertensive and control normotensive Sprague Dawley male rats. After incubation in magnesium-free physiological salt solution (PSS) (O mM magnesium), the increase of extracellular magnesium (1.2; 4.8 mM magnesium) caused a decrease in aortic tone which was significantly greater when endothelium was disrupted. Magnesium-induced relaxation was also more pronounced when endothelial NO production was blocked by 10(-4) M N omega-nitro-L arginine methyl ester (L-NAME). It is suggested that the vasorelaxation induced by extracellular magnesium is linked to the level of aortic basal tension developed in magnesium-free PSS. The endothelium does not seem to be directly implicated in magnesium-induced vasorelaxation in aortas from normotensive rats. However, in DOCA-salt hypertensive rats, the magnesium-induced relaxation of basal tension was less in the intact aorta (though not when the endothelium was disrupted) when the cyclo-oxygenase pathway was blocked by 10(-6) M indomethacin. These data therefore suggest that extracellular magnesium can promote relaxation by endothelium-dependent and cyclo-oxygenase-dependent mechanisms such as the production of relaxing prostacyclin in isolated aorta from DOCA-salt hypertensive rats.
 ...
PMID:Influence of endothelium in the in vitro vasorelaxant effect of magnesium on aortic basal tension in DOCA-salt hypertensive rat. 129 60

Vasorelaxant effects of magnesium (Mg) have been described in man and in animal with arterial hypertension. Some studies have shown relationships between extracellular Mg (magnesium e.c.) and endothelial function. So, our study is designed to determine whether elevated extracellular Mg leads to an endothelium-dependent vasorelaxant effect on contractile tension developed by noradrenaline in isolated aorta from DOCA-salt hypertensive rats. Elevated extracellular Mg (4.8 mM) in the bath significantly depressed the dose-response curve to noradrenaline in aorta with endothelium. Following disruption of endothelium, the vasorelaxant effect of elevated extracellular Mg on contractile response to noradrenaline was greatly inhibited. Furthermore, in presence of L. NG nitroarginine (L-NAME) (10(-4) M), inhibitor of endothelial nitric oxide (NO) biosynthesis, the vasorelaxant effect of extracellular Mg on contractility to noradrenaline was partially inhibited. The addition of sodium nitroprussiate (5 10(-9) M), known to spontaneously release NO, caused the reappearance of Mg vasorelaxation which had disappeared in aorta without endothelium. In conclusion, vascular endothelium seems to play an important role in the Mg-induced depressed contractile response to noradrenaline in isolated aorta from DOCA-salt hypertensive rat. Endothelial NO seems to be implicated in the endothelium-dependent action of extracellular Mg.
 ...
PMID:[In vitro study of the role of endothelium on the vasorelaxant effect of magnesium on the aorta from DOCA-salt hypertensive rats]. 148 62

The contribution of the renin-angiotensin system (RAS) and various endogenous vasoconstrictors on the pressor response to acute N omega-nitro-L-arginine methyl ester (L-NAME) administration (200 micrograms/kg/min) was assessed in anesthetized Wistar rats. Activity of the endogenous RAS was suppressed either by chronic treatment by a nonpeptide angiotensin II (AII) receptor antagonist (losartan) or an angiotensin-converting enzyme inhibitor (ACEI: enalapril), DOCA-salt pretreatment (without previous uninephrectomy), and binephrectomy (36-40 hours before experiments). We also studied the influence of chronic dietary sodium restriction. The role of alpha 1-adrenoceptor activity, endothelin (ET), and eicosanoids was evaluated in rats pretreated by prazosin, phosphoramidon (a nonspecific blocker of the conversion of big ET to ET), indomethacin, and the thromboxane A2 (TXA2) prostaglandin H2 (PGH2)-receptor antagonist SQ 29548, respectively. Finally, we tested the influence of the calcium channel blocker nicardipine on the vasopressor effect of L-NAME. In nonpretreated animals, L-NAME infusion induced an increase in mean arterial pressure (MAP) of 38 +/- 4 mm Hg. Chronic suppression of the RAS by losartan, enalapril, or DOCA did not alter the response to L-NAME, but the effect of L-NAME was moderately blunted in binephrectomized rats. Moderate attenuation (approximately 25%) and to a similar extent of the pressor effect of L-NAME was afforded by the low-sodium diet, phosphoramidon, SQ 29548, and indomethacin, whereas nicardipine markedly blunted by 74% the effect of L-NAME. We conclude that the acute pressor effect of L-NAME is mediated (at least in part) by cyclooxygenase-dependent products (mainly TXA2) and ET, but not by the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Endogenous vasoactive systems and the pressor effect of acute N omega-nitro-L-arginine methyl ester administration. 752 59

NG-nitro-L-arginine methyl ester (L-NAME) and 11-desoxycorticosterone plus salt intake (DOCA-salt) hypertensive rat models were compared to study the possible involvement of model-specific factors in the development of renal angiopathy and left ventricular hypertrophy (LVH). Blood pressure was measured in L-NAME, DOCA-salt hypertensive, and control Wistar rats, and the lesions of nephroangiosclerosis and left ventricular hypertrophy were evaluated after 7 weeks. Arterial wall cyclic guanosine monophosphate, plasma renin activity (PRA), and renal renin storage were assessed in parallel. For the same level of hypertension in the two models, the renal arterial fibrinoid necrotic lesions were significantly more frequent in L-NAME than in DOCA-salt hypertensive rats. In DOCA-salt hypertensive rats, PRA was decreased and arterial cGMP increased compared to controls. In the L-NAME model, arterial cGMP decreased and PRA showed a bimodal distribution in this intermediate stage of hypertensive disease. LVH was observed in DOCA-salt rats and only in the L-NAME rats with a high level of PRA. There was a close correlation between the lesions of nephroangiosclerosis, left ventricular index, and plasma renin activity in L-NAME rats. We therefore suggest that the activation of the renin-angiotensin system participates specifically in the development of the second stage of hypertension during chronic blockade of NO synthase involving nephroangiosclerosis and LVH.
 ...
PMID:Renal hypertensive angiopathy. Comparison between chronic NO suppression and DOCA-salt intoxication. 775 45

The aim of this study was to examine the influence of vascular endothelium on the relaxation induced by increased extracellular Mg2+ concentrations on isolated and noradrenaline-precontracted aorta from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive and normotensive rats. In Mg(2+)-free physiologic salt solution (PSS), addition of Mg2+ (0.1-6.0 nM) caused concentration-dependent relaxation of noradrenaline-precontracted aorta with intact or disrupted endothelium. Mg(2+)-induced relaxation in intact aorta, however, was less in DOCA-salt hypertensive rats than in normotensive rats. When endothelium was disrupted, Mg(2+)-induced relaxation was depressed in aorta from both DOCA-salt hypertensive and normotensive rats. The same observations were made in presence of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor nitric oxide (EDRF/NO) biosynthesis. Mg(2+)-induced relaxation following contraction with noradrenaline was significantly less in intact aorta treated with L-NAME from DOCA-salt hypertensive rats than in intact aorta from normotensive rats. Indomethacin did not affect Mg(2+)-induced relaxation in intact aorta from normotensive rats whereas indomethacin significantly increased it in DOCA-salt hypertensive rats. It is concluded that (1) Mg(2+)-induced relaxation can be mediated by endothelium-dependent mechanisms implicating EDRF/NO; (2) the influence of EDRF/NO is more pronounced on the impaired Mg(2+)-induced relaxation of aorta from DOCA-salt hypertensive rats; (3) Mg(2+)-induced relaxation seems masked by vasoconstrictor prostaglandin release in DOCA-salt hypertensive rats; (4) these differences between normotensive and hypertensive rats could be related to the impaired endothelial function in aorta from DOCA-salt hypertensive rats.
 ...
PMID:Influence of endothelium on Mg(2+)-induced relaxation in noradrenaline-contracted aorta from DOCA-salt hypertensive rat. 808 52

Inhibition of nitric oxide synthase by L-arginine analogues is associated with elevation of blood pressure in rats. Deoxycorticosterone acetate (DOCA)-salt hypertensive rats and DOCA-salt-treated spontaneously hypertensive rats (SHR) overexpress the endothelin-1 gene in blood vessels, and this is associated with severe vascular hypertrophy, whereas SHR do not overexpress endothelin-1 and exhibit limited vascular hypertrophy. In this study malignant hypertension was induced in SHR by chronic administration of the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME), a potent inhibitor of nitric oxide synthase, to determine whether malignant hypertension would result in endothelin-1 gene overexpression in blood vessels and in greater severity of vascular hypertrophy, as found in malignant DOCA-salt-treated SHR. L-NAME treatment induced malignant hypertension in SHR, with a systolic blood pressure of 246 +/- 2 mm Hg, compared with 211 +/- 2 mm Hg (P < .01) in untreated SHR. Plasma renin activity was very high in L-NAME-treated SHR, and their plasma immunoreactive endothelin concentration was slightly but significantly elevated (P < .01). After 3 weeks of treatment, aortic and to a lesser degree mesenteric artery weights were significantly increased in L-NAME-treated SHR compared with untreated SHR. However, cardiac weight and the media cross-sectional area or media width-to-lumen diameter ratio of small arteries from the coronary, renal, mesenteric, or femoral vasculature were not increased in L-NAME-treated SHR in comparison with untreated SHR. The abundance of endothelin-1 mRNA measured by Northern blot analysis was significantly increased in L-NAME-treated SHR in aorta and with less magnitude in the mesenteric arterial tree. The absence of accentuation of cardiac and small artery hypertrophy in malignant hypertension in L-NAME-treated SHR, despite enhanced expression of the endothelin-1 gene in blood vessels, may suggest a direct or indirect inhibitory effect of L-NAME on cardiovascular growth, probably independent of its effects on nitric oxide synthase, counterbalanced in aorta and large mesenteric arteries by the hypertrophic effect of enhanced vascular endothelin-1 gene expression. These results also suggest a role for blood pressure and potentially for nitric oxide in the regulation of endothelin-1 gene expression in blood vessels.
 ...
PMID:Vascular structure and expression of endothelin-1 gene in L-NAME-treated spontaneously hypertensive rats. 859 87

We used Ro 46-8443, non-peptidic antagonist selective of endothelin ETB receptors, to study the role of ETB receptors in rat hypertension models. In normotensive rats, Ro 46-8443 decreased blood pressure, but in SHR and DOCA rats, it induced a pressor effect, due to blockade of ETB-mediated release of nitric oxide since L-NAME prevented it. In rats rendered hypertensive by chronic L-NAME, Ro 46-8443 did not induce a pressor but depressor effect. Thus, in DOCA rats and SHR, Ro 46-8443 reveals a predominant influence of endothelial 'vasorelaxant' ETB receptors, while in normotensive rats the prevailing role of ETB receptors seems to be in mediating a vasoconstrictor tone.
 ...
PMID:The role of ETB receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ETB receptor antagonist Ro 46-8443. 861 87

We have recently shown an enhanced expression of inhibitory guanine nucleotide regulatory proteins Gi alpha-2 and Gi alpha-3 and their respective mRNA in hearts from DOCA-salt hypertensive rats. However, it is not known whether these changes are due to the expressed hypertrophy or hypertension. The present studies were therefore undertaken to investigate this possibility. Hypertension in Sprague-Dawley rats was induced by the oral administration of the arginine analog N(omega)-nitro-L-arginine methyl ester (L-NAME) in their drinking tap water for a period of 4 weeks. The control rats were given plain tap water only. L-NAME-treated rats showed an enhanced blood pressure (190 +/- 9.23 mm Hg; n = 20) compared to control rats (121 +/- 6.3 mm Hg; n = 20). However, heart to body weight ratio was not different in the two groups. Guanosine 5'-o-(3-thiotriphosphate) (GTPgammaS) stimulated adenylyl cyclase activity in heart membranes from both groups, but the extent of stimulation was significantly decreased in L-NAME-treated rats. Similarly, stimulations exerted by isoproterenol, glucagon, NaF, and forskolin on adenylyl cyclase were also diminished in L-NAME-treated rats. On the other hand, the inhibitory effect of low concentrations of GTPgammaS on forskolin-stimulated enzyme activity was significantly enhanced. The extent of oxotremorine-mediated inhibition of adenylyl cyclase was unaltered in both control and L-NAME-induced hypertensive rats. The levels of Gi alpha-2 and Gi alpha-3, but not of stimulatory guanine nucleotide regulatory protein Gs alpha, as determined by immunoblotting, were significantly augmented in L-NAME-treated rats. Northern blot studies revealed a significant increase in Gi alpha-2 and Gi alpha-3 mRNA with no changes in Gs alpha mRNA. These results suggest that the altered expression of Gi alpha proteins and adenylyl cyclase activity in L-NAME-treated rats may be attributed to hypertension and not to hypertrophy.
 ...
PMID:Nitric oxide synthase inhibition by N(omega)-nitro-L-arginine methyl ester modulates G-protein expression and adenylyl cyclase activity in rat heart. 912 16

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.
 ...
PMID:Endothelin: role in hypertension. 983 May 7

We analyzed the effects of a possible interaction between nitric oxide deficiency and mineralocorticoids on the long-term control of blood pressure and renal and endocrine variables. Six groups of uninephrectomized male Wistar rats were used: control animals and rats that received (1) N(G)-nitro-L-arginine methyl ester (L-NAME) subpressor (0.5 mg/100 mL drinking fluid), (2) L-NAME pressor (35 mg/100 mL drinking fluid), (3) deoxycorticosterone acetate (DOCA; 12. 5 mg/wk per rat), (4) DOCA plus L-NAME subpressor, or (5) L-NAME pressor plus DOCA. For all groups, the drinking fluid was tap water or 1% NaCl solution. We measured the time course of tail systolic blood pressure (SBP) and body weight for 3 weeks in all rats. At the end of the experimental period, we measured mean arterial pressure (direct recording) and endocrine and renal variables. Tail SBP rose significantly in the DOCA plus L-NAME subpressor-treated group but remained at normotensive levels in the DOCA-treated group. The addition of L-NAME to the subpressor dose accelerated the blood pressure increase in DOCA-salt hypertensive rats. The simultaneous administration of DOCA and L-NAME increased blood pressure and mortality rates in rats that drank water or saline compared with the rats treated with L-NAME alone. The subpressor dose of L-NAME did not increase blood pressure in saline-drinking rats. We conclude that impaired NO synthesis results in increased sensitivity to the pressor effect of mineralocorticoids in the presence or absence of an increased saline intake. Hence, nitric oxide contributes to the adaptative response to mineralocorticoid excess, perhaps through the facilitation of natriuresis and, thus, control of blood pressure.
 ...
PMID:Interaction between nitric oxide and mineralocorticoids in the long-term control of blood pressure. 1072 May 90


1 2 3 Next >>