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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major characteristic of renal hemodynamics in hypertension is abnormally high resistance of the preglomerular vessel, most likely the afferent arteriole (Af-Art). Although endothelium-derived relaxing factor (EDRF)/nitric oxide (NO) has been studied extensively in large vessels, little is known about its role in Af-Art reactivity. Using isolated microperfused Af-Arts of 12- to 13-week-old spontaneously hypertensive rats (SHRs) and their normotensive control, Wistar-Kyoto (WKY) rats, we examined the effect of acetylcholine (ACh) or N omega-nitro-L-arginine (L-NAME), which stimulates or blocks endothelium-derived NO, respectively. Af-Arts were preconstricted with norepinephrine to 70 +/- 5 and 62 +/- 4% of the control diameter in SHRs and WKY rats, respectively; the intraluminal pressure was kept at either 100 or 70 mm Hg. In SHRs, ACh (1 nM-0.1 mM) added to the Af-Art perfusate caused no vasodilation but tended to decrease the diameter further to 59 +/- 6% of control (N = 8). In contrast, in WKY rats, ACh reversed the luminal diameter to 90 +/- 4% of control (N = 6, p < 0.01 compared with SHRs). Contrary to the responses to ACh, blockade of endothelium-derived NO with L-NAME decreased the basal diameter by 31 +/- 8 and 14 +/- 5% in SHRs and WKY rats, respectively. We conclude that ACh-induced vasodilation is impaired in SHR Af-Art. The impaired response to ACh may be due to factors other than endothelium-derived NO such as endothelium-derived contracting factor (EDCF).
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PMID:Impaired response to acetylcholine despite intact endothelium-derived relaxing factor/nitric oxide in isolated microperfused afferent arterioles of the spontaneously hypertensive rat. 128 64

It is well established that acute systemic blockage of L-arginine conversion to nitric oxide by NW-nitro-L-arginine methyl ester (L-NAME) and other substituted analogs of L-arginine produces vasoconstriction and elevates the blood pressure. The present study in rats reports that chronic L-NAME injections (185 mumol/L/kg body weight, intraperitoneally; every 12 h) for 4 days produces sustained arterial hypertension which is fully and rapidly reversed by acute administration of excess L-arginine. The magnitude of the hypertension is not different between L-NAME treated rats fed normal or high sodium diets. The results from this simple experimental model suggest that chronic blockade of nitric oxide synthesis results in sustained arterial hypertension that is not enhanced by sodium loading.
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PMID:Sustained hypertension in the rat induced by chronic blockade of nitric oxide production. 128 42

Endothelium-derived relaxing factor has been shown to regulate renal blood flow, and inhibition of its synthesis increases blood pressure and renal vascular resistance and decreases renal blood flow. Using the substrate antagonist NW-nitro-L-arginine methyl ester (L-NAME), we tested whether renal vasoconstriction induced by endothelium-derived relaxing factor synthesis inhibition could be mediated in part by angiotensin II. In 14 control rats, 10 mg/kg body wt L-NAME increased blood pressure from 106 +/- 6 to 126 +/- 6 mm Hg (p < 0.001), increased renal vascular resistance by 74% (from 19.3 +/- 2.6 to 33.6 +/- 2.9 resistance units), and decreased renal blood flow by 34% (from 5.9 +/- 0.5 to 3.9 +/- 0.3 ml.min-1.g kidney wt-1, p < 0.005). When six rats were treated with 10 mg/kg body wt of the angiotensin receptor antagonist DuP 753, L-NAME increased blood pressure from 84 +/- 4 to 106 +/- 4 mm Hg (p < 0.001); however, renal vascular resistance increased by only 27% (from 13 +/- 2 to 17 +/- 3 resistance units, p < 0.01; p < 0.05 different from control value) and renal blood flow was unchanged. Likewise, after pretreatment of six rats with 32 micrograms/100 g body wt of the angiotensin converting enzyme inhibitor enalaprilat, L-NAME increased blood pressure from 88 +/- 5 to 124 +/- 6 mm Hg (p < 0.001) and renal vascular resistance by 54% (from 12 +/- 1 to 18 +/- 3 resistance units, p < 0.01; p < 0.05 different from control value) but renal blood flow was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Nov
PMID:Angiotensin dependence of endothelium-mediated renal hemodynamics. 133 Sep 22

To determine whether the release of endothelium-derived relaxing factor (EDRF) is sympathetically mediated, we studied the effects of beta-blockade by propranolol, ganglionic blockade with hexamethonium, or mechanical pithing on the blood pressure response to EDRF inhibition in anesthetized rats. We inhibited EDRF with 10 mg/kg of either NG-monomethyl-L-arginine (L-NMMA) or N omega-nitro-L-arginine-methyl ester (L-NAME). In controls, L-NMMA and L-NAME increased blood pressure by 14 +/- 1 (p less than 0.01) and 22 +/- 2 mm Hg (p less than 0.01), respectively. Propranolol lowered blood pressure from 98 +/- 3 to 72 +/- 4 mm Hg without altering the response to L-NAME (delta 26 +/- 3). This response correlated with the resting blood pressure (r = 0.87; p less than 0.001). Hexamethonium (25 mg/kg) lowered blood pressure from 118 +/- 6 to 85 +/- 4 mm Hg but did not change the response to L-NMMA (delta 15 +/- 1). In pithed rats, blood pressure was lowered, but the pressor response to L-NAME was unchanged. When blood pressure was returned to normotensive levels by angiotensin II, norepinephrine, or phenylephrine, L-NAME increased blood pressure by 50 +/- 2, 68 +/- 8, and 109 +/- 7 mm Hg, respectively (p less than 0.001). We conclude that an intact autonomic nervous system is not needed for the pressor response to EDRF inhibition. The enhanced response in pithed rats treated with vasoconstrictors may be due to removal of the buffering effect of the baroreceptors and the absence of EDRF, which would oppose vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Jun
PMID:Sympathetic modulation of endothelium-derived relaxing factor. 135 May 73

Homozygous male Brattleboro rats were given a solution of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) to drink for a period of 7 days. There was a persistent elevation of mean arterial blood pressure, accompanied by a significant hindquarters vasoconstriction. Within 9 h of withdrawal of L-NMMA all variables were not different from pre-L-NMMA values. Brattleboro rats (n = 3) which had been drinking NG-nitro-L-arginine methyl ester (L-NAME) solution (0.05 mg ml-1) for 5-6 months showed an increased blood pressure which reversed to normal within 48 h after withdrawing the L-NAME. Thus, inhibition of nitric oxide synthesis leads to long-lasting, but reversible, hypertension.
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PMID:Nitric oxide synthase inhibitors cause sustained, but reversible, hypertension and hindquarters vasoconstriction in Brattleboro rats. 137 33

Nitric oxide (NO) and atrial natriuretic factor (ANF) cause vascular relaxation by generating cyclic guanosine monophosphate (cGMP) via activation of the soluble and particulate guanylate cyclases, respectively. The chronic effects of NG-nitro-L-arginine methyl ester (L-NAME), an L-arginine antagonist and NO synthase inhibitor, on the blood pressure and plasma and aortic cGMP levels of rats were tested. Wistar rats (n = 10 per group) were given doses of L-NAME (0, 1, 5, 10, 20, 50, and 100 mg/kg.d) by gavage twice a day for 4 wk. Chronic L-NAME induced a time- and dose-dependent increase in blood pressure. The total heart weight/body weight ratio did not change in any group, despite the hypertension. The plasma levels of cGMP did not change significantly in any group, and were correlated with the plasma ANF levels (r = 0.51, P less than 0.0001). Aortic cGMP decreased in negative correlation with increasing L-NAME from 0 to 10 mg/kg.d, culminating in a 10-fold drop arterial wall cGMP. The aortic cGMP content of rats in the four highest dose groups (from 10 to 100 mg/d) tended to increase slightly and was positively correlated with endogenous ANF (r = 0.48, P less than 0.002, n = 40). Intravenous L-arginine decreased arterial blood pressure and reversed the decline in aortic cGMP. Exogenous ANF and sodium nitroprusside both significantly increased aortic cGMP. Neither the arterial wall concentrations of cGMP-dependent kinase nor cAMP was changed by L-NAME. Thus, chronic blockade of NO synthase with L-NAME induces a dose-dependent increase in blood pressure and decrease in aortic cGMP. The in vivo basal aortic cGMP seems to be mainly dependent on NO synthase: soluble guanylate cyclase activity and to a minor extent on particulate guanylate cyclase activity.
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PMID:Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase. 137 15

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.
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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

Inhibition of the production of the endothelium-derived relaxing factor (EDRF) nitric oxide using N omega-nitro-L-arginine methyl ester (L-NAME) increases blood pressure (BP) and decreases renal blood flow (RBF), suggesting that basal EDRF can modulate both systemic resistance and renal perfusion. We tested whether L-NAME inhibition of EDRF could also change the autoregulation of RBF. Blood pressure and RBF were measured in Inactin-anesthetized Sprague-Dawley rats. A bolus of 10 mg/kg body wt of L-NAME produced the maximum pressor response (23 +/- 3 mmHg) and blocked acetylcholine-induced renal vasodilation. In control rats, sequential changes in renal perfusion pressure showed that RBF was well autoregulated down to 95 +/- 2 mmHg. L-NAME increased BP, decreased RBF by 33% (P less than 0.005), and increased renal vascular resistance twofold. Although RBF was decreased, the kidney was still able to autoregulate RBF, although reset around the lower flow. Acute hypertension by carotid occlusion and vagotomy increased BP by 26 +/- 6 mmHg (P less than 0.005) and slightly increased RBF, while autoregulation was maintained. The pressor response to L-NAME was amplified to 38 +/- 6 mmHg (P less than 0.001), but RBF decreased by 35% (P less than 0.01). Autoregulation of RBF was maintained, although reset around the lower flow. We conclude that, although endothelial EDRF production may help maintain RBF, it does not seem to mediate the intrinsic autoregulatory responses of the renal vasculature to altered renal perfusion pressure.
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PMID:Endothelium modulates renal blood flow but not autoregulation. 162 18

The vascular endothelium plays an essential role in regulating the contractility of the adjacent smooth muscle cell through its secretory and metabolic properties. One of these well known properties is the conversion of angiotensin I into angiotensin II. But the endothelium also secretes at least three compounds able to diffuse to the smooth muscle cell and exerting a paracrine action: these are the prostacyclin (PGI2), the endothelium derived relaxing factor (EDRF) and the endothelin 1. The secretion of these different vasoactive compounds by endothelial cells is triggered by mechanical events, such as the shear stress, or by the effect of several humoral factors locally released, for example from platelets. The compound NO (nitric oxide) is produced by the endothelial enzyme NO synthase from its precursor L-arginine, and is responsible for the vasodilatory and antiplatelets properties of EDRF. NO, by activating the soluble guanylate cyclase in the smooth muscle cell, is responsible for the endothelium dependent vasodilatation. We observed in an isolated perfused rat kidney that the compound L-NAME (NG-monomethyl-L-arginine methyl ester), a competitive inhibitor of NO synthase blocking the production of NO, induces renal vasoconstriction and inhibits renin release. This suggests that not only the renal vasoconstriction but also the renal vasodilatation are active processes, permanently regulated by vasoactive compounds such as EDRF. It seems also that EDRF plays an important role in maintaining the secretion of renin. It can be hypothetized that an abnormality in the release or fate of EDRF might perhaps contribute to high blood pressure, by both a direct effect on the vascular tone and an indirect effect on the release of renin, which in turn regulates also the renal and systemic hemodynamics.
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PMID:[Control of vascular tone by the endothelium: the coupling active vasodilation in the kidney to renin secretion]. 163 4

The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg-1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect.
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PMID:Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure. 175 May 17


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