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

Endogenous nitric oxide is an important modulator of vascular smooth muscle tone. The role of nitric oxide in the vascular adaptation to systemic hypertension was examined by using N omega-monomethyl-L-arginine (L-NMMA; 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused i.v. into several rat models of acute and chronic systemic hypertension. The response to L-NMMA was compared either in uninephrectomized Sprague-Dawley rats treated with deoxycorticosterone on either a high- or low-sodium diet or in untreated uninephrectomized rats on normal chow. Hypertensive deoxycorticosterone rats had a significantly greater pressor response to L-NMMA (139 +/- 2 to 169 +/- 3 mm Hg; N = 9) than did normotensive uninephrectomized rats (112 +/- 4 to 129 +/- 3 mm Hg; N = 7) or deoxycortisterone treated rats on a low-sodium diet (108 +/- 2 to 121 +/- 3 mm Hg; N = 9). By contrast, hypertension induced by the vasoconstrictor angiotensin II did not have an enhanced response (134 +/- 3 to 154 +/- 4 mm Hg; N = 7) nor did spontaneously hypertensive rats (164 +/- 4 to 175 +/- 4 mm Hg; N = 6). This dose of L-NMMA had minimal effects on renal hemodynamics in the normotensive and hypertensive animals, except for those receiving angiotensin II where it led to substantial reductions of inulin and para-aminohippurate clearance. In conclusion, these data point to a role for nitric oxide in the vascular adaptation to volume-mediated hypertension, an effect that was not observed in vasoconstrictor-induced hypertension.
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PMID:Endothelium-derived relaxing factor and the vascular reply to systemic hypertension. 177 87

The Andean population of Ecuador is exposed to major risk factors associated with pregnancy-induced hypertension (PIH). The disease is very frequent, and perinatal and maternal death rates are high. Recently a causal relationship has been suggested between dietary calcium deficiency and PIH, with the proposal that calcium supplements be given throughout pregnancy in order to prevent the disease. This article reviews a series of clinical tests carried out over a six-year period which have demonstrated that calcium supplementation is an effective low-cost measure for reducing the frequency of PIH in women whose intake of the mineral is low. It is not yet known how calcium reduces the risk of PIH. It is suggested that adequate intake of the mineral keeps serum levels of calcium within its narrow physiological limits; these are crucial for the synthesis of nitric oxide in the vascular endothelium, a substance that appears to be responsible for maintaining the vasodilatation that characterizes normal pregnancy. However, before the general use of calcium supplements can be recommended, it will be necessary to conduct epidemiological studies on larger numbers of women.
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PMID:[Use of calcium for the prevention of pregnancy-induced hypertension]. 182 58

1. Nitric oxide (NO) is a major component of endothelium-derived relaxing factor (EDRF) the synthesis of which from L-arginine can be inhibited by NG-monomethyl-L-arginine (L-NMMA). To assess whether basal NO tone is different in experimental hypertension, the haemodynamic effects of L-NMMA have been compared in anaesthetized spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats in which autonomic reflexes were blocked by ganglion blockade. 2. Bolus intravenous injections of L-NMMA, 1-30 mg kg-1, but not D-NMMA, 1-30 mg kg-1, induced dose-related increases in mean arterial pressure and decreases in conductances in the renal, carotid, hindquarters and mesenteric vascular beds in both SH and WKY rats. Although the different vascular beds varied in their maximum responses to L-NMMA, there were neither qualitative nor quantitative differences between the two rat strains in this respect. 3. The effects of L-NMMA, 30 mg kg-1, i.v. on all parameters were rapidly and completely reversed by L-arginine, 30 mg kg-1, i.v., in both SH and WKY rats. 4. The results indicate that NO derived from L-arginine exerts a powerful vasodilator tone in both anaesthetized, ganglion-blocked SH and WKY rats. Although NO appears to contribute differentially to tone in the different vascular beds, there were no major differences between the two rat strains in this respect. Hence a reduced NO tone to the vasculature is unlikely to be a major factor contributing to the elevated blood pressure in the adult SH rat.
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PMID:Haemodynamic responses to NG-monomethyl-L-arginine in spontaneously hypertensive and normotensive Wistar-Kyoto rats. 185 13

The endothelium-derived relaxing factor (EDRF) is nitric oxide (NO) or a closely related nitrosothiol derivative, and is formed from the amino acid, L-arginine. NO is rapidly inactivated locally, released into the blood stream and instantly destroyed by haemoglobin. EDRF-NO and NO generated from vasodilator nitrates work by activation of soluble guanylate cyclase, elevating cyclic guanosine monophosphate (GMP) levels to cause vasodilatation and inhibition of platelet aggregation. Endothelium-dependent vasodilatation is attenuated in hypertension, atherosclerosis and diabetes through either loss of endothelium or deficient formation of EDRF-NO. In these conditions exogenous nitrates may substitute for a failing endogenous mechanism.
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PMID:Endogenous nitrates--implications for treatment and prevention. 187 72

Key discoveries in the past decade revealed that the endothelium can modulate the tone of underlying vascular smooth muscle by the synthesis/release of potent vasorelaxant (endothelium-derived relaxing factors; EDRF) and vasoconstrictor substances (endothelium-derived contracting factors; EDCF). It has become evident that the synthesis and release of these substances contribute to the multitude of physiological functions the vascular endothelium performs. Accumulating evidence suggests that at least one of the EDRFs is identical with nitric oxide (NO) or a labile nitroso compound, which is produced from L-arginine by an NADPH- and Ca(2+)-dependent enzyme, arginine oxidase. The existence of more than one chemically distinct EDRF has been proposed, including an endothelium-derived hyperpolarizing factor (EDHF). The target of EDRF (NO) is soluble guanylate cyclase (increase in cyclic GMP) while EDHF appears to activate a K(+)-channel in vascular smooth muscle. Recent data suggest that muscarinic receptor subtypes selectively mediate the release of EDRF(NO) (M2) and EDHF (M1). EDRF(NO) affects not only the underlying vascular smooth muscle, but also platelets, inhibiting their aggregation and adhesion to the endothelium. The antiaggregatory effect of EDRF is synergistic with prostacyclin, so their combined release may represent a physiological mechanism aimed at preventing thrombus formation. An additional proposed biological function of EDRF(NO) is cytoprotection by virtue of scavenging superoxide radicals. The endothelium can also mediate vasoconstriction by the release of a variety of endothelium-derived contracting factors (EDCF). Other than the unique peptide endothelin, the nature of EDCFs has not yet been firmly established. Autoregulation of cerebral and renal blood flow and hypoxic pulmonary vasoconstriction may represent the physiological role of endothelium-dependent vasoconstriction. Growing evidence indicates that the endothelium can serve as a unique mechanoreceptor, sensing and transducing physical stimuli (e.g., shear forces, pressure) into changes in vascular tone by the release of EDRFs or EDCFs. In physiological states, a delicate balance exists between endothelium-derived vasodilators and vasoconstrictors. Alterations in this balance can result in local (vasospasm) and generalized (hypertension) increase in vascular tone and also in facilitated thrombus formation. Endothelial dysfunction may also contribute to the pathophysiology of angiopathies associated with hypercholesterolemia and atherosclerosis.
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PMID:Endothelium-derived relaxing and contracting factors. 187 96

Endothelium-derived relaxing factor (EDRF), recently identified as nitric oxide (NO), has been shown to be released by glomerular endothelial cells and might influence the glomerular microcirculation. To examine this hypothesis, we studied in rats the renal effect of acute administration of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthesis. Adult male Munich-Wistar rats were studied before and after intravenous administration of either pure saline or a bolus injection of L-NMMA (20 mg) followed by a continuous infusion of the inhibitor (0.4 mg/min). Although saline alone had no effect on systemic or glomerular hemodynamics, L-NMMA promoted marked systemic hypertension, glomerular arteriolar vasoconstriction, and glomerular hypoperfusion. Since efferent resistance was disproportionately increased, glomerular hydraulic pressure was also markedly elevated. The glomerular ultrafiltration coefficient (Kf) fell to 42% of control. Single-nephron glomerular filtration rate was unaffected. Striking polyuria was also observed. These findings suggest that EDRF exerts a basal relaxing effect on the glomerular microcirculation.
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PMID:Effects of acute nitric oxide inhibition on rat glomerular microcirculation. 187 54

1 We investigated the peripheral haemodynamic effects of human alpha-calcitonin gene-related peptide (CGRP) following administration of endothelin-1 or NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide production, in conscious, chronically-instrumented, Long Evans rats. 2 Infusion of endothelin-1 (3 nmol kg-1 h-1) caused hypertension, bradycardia and renal, mesenteric and hindquarters vasoconstrictions. Co-infusion of human alpha-CGRP (1.5 nmol kg-1 h-1) reduced the hypertension and abolished the hindquarters vasoconstriction caused by endothelin-1 but the renal and mesenteric vasoconstrictor actions of endothelin-1 were not affected. 3 Infusion of human alpha-CGRP (15 nmol kg-1 h-1) in the presence of endothelin-1 caused hypotension and hyperaemic vasodilatation in the hindquarters; the mesenteric vasoconstrictor effects of endothelin-1 were diminished, but there was only a transient reversal of the renal vasoconstrictor effects of endothelin-1. 4 Pretreatment with the non-peptide angiotensin II receptor antagonist, DuP 753 (10 mg kg-1), caused slight hypotension associated with renal, mesenteric and hindquarters vasodilatations, but DuP 753 did not affect responses to endothelin-1 infusion. However, under these conditions co-infusion of human alpha-CGRP (15 nmol kg-1 h-1) caused a sustained reversal of the renal vasoconstrictor effects of endothelin-1. 5 These results indicate that the failure of human alpha-CGRP to cause sustained reversal of the renal vasoconstrictor effects of endothelin-1 in the absence of DuP 753 was due to activation of the reninangiotensin system (possibly as a consequence of the hypotension). 6. In the second experiment, L-NAME (l0mgkg-1) caused renal, mesenteric and hindquarters vasoconstrictions similar to those seen in the presence of endothelin-1. However, the renal vasoconstrictor effects of L-NAME were reversed completely by human alpha-CGRP (l5nmolkg- h-1), even though the latter caused hypotension comparable to that seen in the presence of endothelin-1. These results are consistent with a lack of functional activation of the renin-angiotensin system by human alpha-CGRP in the presence of L-NAME. 7. The vasoconstrictor effects of L-NAME on the hindquarters were completely reversed by infusion of human alpha-CGRP, but hindquarters flow and vascular conductance did not rise above baseline levels. Hence these results indicate the hindquarters hyperaemic vasodilator effects of human alpha-CGRP seen in the presence of endothelin-1 were contributed to by nitric oxide-mediated mechanisms.
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PMID:Haemodynamic effects of human alpha-calcitonin gene-related peptide following administration of endothelin-1 or NG-nitro-L-arginine methyl ester in conscious rats. 187 60

Stroke-prone spontaneously hypertensive rats (SHRSP) develop severe hypertension and cerebrovascular lesions. We investigated the influence of dietary supplementation with L-arginine, an amino acid precursor of endothelium-derived nitric oxide, on blood pressure and stroke in these rats. L-Arginine, administered in the saline drinking solution at 2 or 6 g/l starting at 8.7 weeks of age, was without effect on blood pressure, cerebrovascular lesions, or longevity despite continuous treatment through 14 weeks of age. These findings do not support a beneficial influence of dietary arginine in the cerebrovascular pathology of SHRSP.
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PMID:Dietary arginine fails to protect against cerebrovascular damage in stroke-prone hypertensive rats. 188 30

Acetylcholine produces less dilatation of pial arterioles in stroke-prone spontaneously hypertensive rats (SHRSP) than in normotensive (WKY) rats. Responses of cerebral vessels to acetylcholine and bradykinin appear to involve different mechanisms. Our first goal was to determine whether responses of pial arterioles to bradykinin are impaired in SHRSP. Diameter of pial arterioles (20-60 microns) was measured using intravital microscopy in WKY rats and SHRSP (9-12 months old). Superfusion of bradykinin (3 x 10(-7) M) dilated pial arterioles by 35 +/- 6% (mean +/- SEM) in WKY rats, but only 21 +/- 3% in SHRSP (p less than 0.05 versus WKY rats). Both nitric oxide (5 x 10(-7) M) and nitroglycerin (10(-5) M) produced similar vasodilatation in WKY rats and SHRSP. Our second goal was to determine whether alteration of postreceptor mechanisms contributes to impairment of endothelium-dependent cerebral vasodilatation in SHRSP. Calcium ionophore A23187 (10(-5) M) produced more vasodilatation in WKY rats than in SHRSP (32 +/- 8% versus 9 +/- 4%, p less than 0.05). Responses to A23187 (10(-5) M) were inhibited by indomethacin (46 +/- 13% versus 15 +/- 5%, p less than 0.05) in WKY rats, whereas responses to A23187 (10(-6) M) were potentiated modestly by indomethacin (-3 +/- 2% versus 4 +/- 2%, p less than 0.05) in SHRSP.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1991 May
PMID:Endothelium-dependent responses of cerebral blood vessels during chronic hypertension. 190 37

The nitrovasodilators, nitroglycerin and sodium nitroprusside, cause both arterial and venous smooth muscle dilation by the intracellular release of nitric oxide. Nitric oxide activates guanylate cyclase, resulting in an accumulation of cyclic GMP. The endogenous formation of nitric oxide results in vasodilatory activity similar to the nitrovasodilators. Nitroglycerin is commonly used in the treatment of angina pectoris because of its ability to decrease myocardial oxygen consumption. Most likely, this response occurs as a result of a reduction in preload, which can decrease arterial wall tension and improve coronary blood flow. This pharmacologic effect warrants the use of nitroglycerin in the treatment of myocardial ischemia or infarction, congestive heart failure, and hypertension. Sodium nitroprusside is effective in reducing arterial blood pressure in hypertensive crisis as a result of systemic vasodilation leading to a reduction in preload and afterload. Sodium nitroprusside is not as effective in the treatment of angina pectoris or in diminishing of myocardial ischemia because it does not preferentially improve blood flow to ischemic myocardium over nonischemic myocardium. Inhibition of platelet aggregation has been demonstrated with these drugs, but the clinical applications need further investigation. Nursing interventions for the patient on nitrovasodilator therapy include careful hemodynamic monitoring and drug infusion, along with elimination of physical and emotional stimuli that can aggravate the patient's underlying pathology.
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PMID:Pharmacology of the nitrovasodilators. Antianginal, antihypertensive, and antiplatelet actions. 190 76


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