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

We investigated the role of nitric oxide (NO)-dependent and NO-independent mechanisms in mediation of renal vasodilatory responses to bradykinin in spontaneously hypertensive rats (SHR), rats with angiotensin II-induced hypertension (200 ng/min i.p. for 6 days) and the corresponding normotensive control Wistar-Kyoto (WKY) rats and sham-infused rats. To this end, we contrasted the effects of arterial injections of bradykinin and other vasodilators, acetylcholine and sodium nitroprusside, on perfusion pressure and output of cyclic GMP in isolated kidneys perfused with Krebs bicarbonate buffer containing phenylephrine, both with and without N omega-nitro-L-arginine (L-NOARG) (50 microM), an inhibitor of NO synthetase. In kidneys perfused without L-NOARG, all agonists increased the output of cyclic GMP and reduced perfusion pressure, indicative of vasodilation. In kidneys perfused with L-NOARG, vasodilatory responses to bradykinin and acetylcholine were attenuated, and associated effects on output of cyclic GMP were abolished, suggesting dependency on NO synthesis. Irrespective of whether kidneys were perfused with or without L-NOARG, kidneys of SHR were more responsive than kidneys of WKY rats with regard to bradykinin-induced vasodilation. In contrast, vasodilatory responsiveness to bradykinin was nearly equal in perfused kidneys of rats with angiotensin II-induced hypertension and in normotensive controls. Also, vasodilatory responsiveness to acetylcholine and sodium nitroprusside was similar in kidneys of normotensive and hypertensive rats. These data suggest that the renal vasculature of SHR is uniquely and selectively hyperresponsive to bradykinin, with regard to both the NO-dependent and NO-independent vasodilatory actions.
Hypertension 1991 Nov
PMID:Increased vascular responsiveness to bradykinin in kidneys of spontaneously hypertensive rats. Effect of N omega-nitro-L-arginine. 165 72

This study examined the contribution of nitric oxide (NO) to the susceptibility or resistance to the hypertensive effects of high sodium chloride (8.0% NaCl) intake in young Dahl/Rapp salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats. Using NG-monomethyl-L-arginine (L-NMMA) as a probe for NO production in vivo, we found that increasing dietary sodium chloride increased NO activity in salt-resistant rats, but not in salt-sensitive rats. Exogenous L-arginine, the substrate for NO synthesis, decreased blood pressure to normotensive levels in salt-sensitive rats made hypertensive for 2 wk from 8.0% NaCl chow. D-arginine had no effect on blood pressure of these rats and L-arginine did not change blood pressure of salt-resistant rats. Intraperitoneal injections of L-arginine and its precursor, L-citrulline, and oral L-arginine, but not D-arginine, prevented the increase in blood pressure in salt-sensitive rats on the high salt chow over 2 wk of observation. In contrast, L-arginine did not alter the development of hypertension in spontaneously hypertensive rats. Mean urinary cGMP levels were higher in salt-sensitive rats on oral L-arginine than salt-sensitive rats on D-arginine. Infusion of L-NMMA acutely decreased, whereas intravenous L-arginine rapidly increased, urinary cGMP in both groups. L-arginine and L-citrulline increased production of NO and prevented salt-sensitive hypertension in Dahl/Rapp rats.
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PMID:L-arginine abrogates salt-sensitive hypertension in Dahl/Rapp rats. 165 45

The aim of the present study was to examine the involvement of the sympathetic nervous system in the generation or release of vascular nitric oxide. In urethane-anesthetized rats, the administration of the novel nitric oxide synthesis inhibitor L-N-nitro arginine (LNA) (0.02 mmol/kg i.v.) increased mean arterial pressure and renal, mesenteric, and hindquarter vascular resistances. The intravenous administration of L-arginine (60 mg/kg plus 12 mg/kg/min i.v.) produced small reductions in arterial pressure and vascular resistances and abolished the hemodynamic effects of LNA. Pretreatment with the ganglion blocking agent chlorisondamine lowered mean arterial pressure and vascular resistances, abolished the LNA-induced pressor and renal vasoconstrictor response, and attenuated the increases in mesenteric and hindquarter resistances. In contrast, the vasodilator hydralazine lowered mean arterial pressure and vascular resistances to levels equivalent to that of ganglionic blockade; however, the subsequent administration of LNA still produced significant increases in arterial pressure and regional vascular resistances. In ganglion-blocked rats in which pressure and vascular resistances were returned to normal levels by infusion of arginine vasopressin or phenylephrine, the pressor and vasoconstrictor effects of LNA were restored. However, phenylephrine was significantly more efficacious and markedly exaggerated the action of LNA. These results suggest that the sympathetic nervous system plays an important role in modulating the synthesis or release of vascular nitric oxide through the effects of 1) normal sympathetic discharge, 2) humoral activation of alpha-adrenergic receptors, and 3) vascular tone per se.
Hypertension 1991 Jun
PMID:Role of sympathetic nerve activity in the generation of vascular nitric oxide in urethane-anesthetized rats. 167 5

Norepinephrine-induced responses in isolated perfused mesenteric vascular bed from normotensive and renovascular hypertensive rats were examined in the presence of adenosine diphosphate (ADP, 2 x 10(-6) M). Responses to norepinephrine were significantly greater in vessels from hypertensive rats. Norepinephrine-induced contractions increased after the removal of endothelium. N omega-Nitro-L-arginine (L-NOARG), a potent inhibitor of nitric oxide formation, similarly increased contractions. The greatest responses were obtained, however, after treatment of the vascular segments with methylene blue. The presence of ADP caused significant endothelium-dependent decreases in contractions. Although decreases caused by ADP in vessels with endothelium after treatment with L-NOARG were not statistically significant, a tendency to decreased responses seems to suggest that L-NOARG diminishes but does not completely prevent the effect of ADP in mesenteric vessels. Methylene blue partially reduced the endothelium-dependent ADP-induced relaxant effects in sham-operated nephrectomized rats. A tendency to increased contractions to norepinephrine was observed in the presence of ADP after removal of endothelium. Thus, in the mesenteric resistance arteries of the rat under stimulation by ADP, it appears that nitric oxide released from L-arginine and the activity of soluble guanylate cyclase account only in part for the endothelium-dependent decreased responses to norepinephrine. When nitric oxide formation or soluble guanylate cyclase activity are depressed simultaneously with endothelium damage, ADP released from platelets or red blood cells may be an important factor that acts synergically with vasoconstrictor stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Endothelium-dependent and endothelium-independent effects of adenosine diphosphate in renovascular hypertension. 173 85

We assessed the vasodilator effect of endothelium-derived nitric oxide by inhibiting its formation with NG-monomethyl L-arginine (LNMMA) on systemic and regional hemodynamics in conscious, normotensive rats, using the radioactive microsphere technique. In rats injected with 10 mg/kg LNMMA (n = 8), mean blood pressure increased by 16.2 +/- 2.6 mm Hg, and heart rate decreased by 54.3 +/- 16.7 beats per minute. In comparison with rats injected with 5% dextrose (n = 14), cardiac index was lower by 35.6% (p less than 0.01), and total peripheral vascular resistance was higher by 51.6% (p less than 0.01); regional blood flows were lower and vascular resistance higher in most organs. Changes were significant in the heart, kidney, stomach, large intestine, skin, and adrenals (p less than 0.05). Preinjection of 100 mg/kg L-arginine prevented the pressor response but only partially attenuated the other hemodynamic effects of LNMMA. Combination of LNMMA with the bradykinin antagonist (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg)trifluoroacetic acid (50 micrograms/min for 5 minutes) did not produce systemic or regional effects different from those obtained with LNMMA alone. Combination of LNMMA with indomethacin (10 mg/kg) resulted in additional changes in the cerebral circulation, blood flow decreasing by an additional 44.2% (p less than 0.01) and vascular resistance increasing by 75.3% (p less than 0.01) compared with changes produced by LNMMA alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Inhibition of nitric oxide, bradykinin, and prostaglandins in normal rats. 173 88

Although endothelium-derived prostaglandin I2 stimulates renin release, exogenous endothelium-derived relaxing factor (EDRF) can inhibit it. To characterize the role of EDRF as an endogenous regulator of renin release, we inhibited or stimulated its production in rat renal cortical slices in vitro. Renin concentration in the incubation medium was determined by radioimmunoassay for angiotensin I (Ang I) generation. NG-Monomethyl-L-arginine (LNMMA) (10(-4) M), which blocks EDRF formation, significantly enhanced basal renin release from kidney slices by more than 50% in control medium (40.0 +/- 14.3 ng Ang I/hr/mg/30 min; p less than 0.01) or in medium treated with 1.6 x 10(-5) M meclofenamate (50.8 +/- 8.4 ng Ang I; p less than 0.025). Isoproterenol (10(-5) M)-stimulated renin release (40.0 +/- 14.3 ng Ang I; p less than 0.02) was not modified by LNMMA; addition of L-arginine (10(-5) M), the precursor of EDRF, did not change basal but blocked isoproterenol stimulation of renin. Nitroprusside (10(-5) M) completely reversed melittin-stimulated renin release. Endothelin-1, an endothelium-derived vasoconstrictor, inhibits renin release and stimulates EDRF and prostaglandin synthesis. To determine whether any of the renin-inhibiting effect of endothelin-1 was due to its stimulation of EDRF, we compared the effect of endothelin-1 on cortical slices with and without EDRF inhibition. Endothelin-1 (10(-7) M) decreased renin by 36.7 +/- 10.9 ng Ang I (p less than 0.01) compared with controls, and the response was the same after either LNMMA or hemoglobin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Feb
PMID:Nonprostanoid endothelium-derived factors inhibit renin release. 173 97

We investigated the role of kinins in the acute depressor effect of captopril and ramiprilat in spontaneously hypertensive rats. Since the vasodepressor action of kinins may be linked to the generation of prostaglandins and endothelium-derived relaxing factors, we also investigated the role of prostaglandins and nitric oxide in the blood pressure reduction caused by angiotensin converting enzyme inhibitors. To this end, we contrasted the hypotensive effects of captopril (10 mg/kg i.v.), ramiprilat (2 mg/kg i.v.), and the angiotensin II antagonist DuP 753 (30 mg/kg i.v.) in spontaneously hypertensive rats with and without pretreatment with a kinin antagonist (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Phe-Thi-Arg-trifluoroacetic acid) (200 micrograms/kg/min i.v.), an inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine) (15 mg/kg + 10 mg/kg/hr i.v.), or an inhibitor of prostaglandin synthesis (indomethacin) (10 mg/kg i.v.). The kinin antagonist did not affect blood pressure in spontaneously hypertensive rats but did attenuate the hypotensive effect of captopril and ramiprilat; the kinin antagonist did not minimize the depressor action of DuP 753. The nitric oxide synthesis inhibitor increased blood pressure in spontaneously hypertensive rats and attenuated the hypotensive effect of captopril, ramiprilat, and DuP 753, but it did not impede the hypotensive effect of sodium nitroprusside. Pretreatment of hypertensive rats with indomethacin did not modify the acute hypotensive effect of ramiprilat or captopril. These data suggest a contribution of endogenous kinins and nitric oxide to the acute antihypertensive effect of captopril and ramiprilat in spontaneously hypertensive rats and of nitric oxide to the hypotensive effect of DuP 753.
Hypertension 1992 Feb
PMID:Kinins, nitric oxide, and the hypotensive effect of captopril and ramiprilat in hypertension. 173 47

Physiological importance in vasodilator innervation alleviating noradrenergic neurogenic vasoconstriction has not been clarified. Isolated monkey mesenteric artery strips denuded of the endothelium responded to nerve stimulation by electrical pulses or nicotine with a contraction, which was potentiated by Ng-nitro-L-arginine, a nitric oxide synthesis inhibitor, but not by the D-enantiomer. The potentiation was abolished by L-arginine. NG-Nitro-L-arginine did not potentiate the response to exogenous norepinephrine nor did it increase the release of [3H]norepinephrine from adrenergic nerves electrically stimulated. The contraction was reversed by treatment with phentolamine and guanethidine to a relaxation, which was abolished by NG-nitro-L-arginine. The inhibition was reversed by L- but not D-arginine. The relaxant response was not influenced by atropine, timolol, or indomethacin. These findings strongly suggest the importance of reciprocal nitric oxide-related (nitroxidergic) vasodilator and noradrenergic vasoconstrictor innervation in the regulation of monkey arterial tone.
Hypertension 1992 Feb
PMID:Mechanism of neurally induced monkey mesenteric artery relaxation and contraction. 173 50

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

Endothelial cells contain an enzyme(s) which produces nitric oxide from L-arginine in response to a variety of mechanical stimuli as well as to autacoids and local and circulating hormones. Nitric oxide is a potent vasodilator and inhibitor of platelet function; it exerts its effects via activation of soluble guanylate cyclase and subsequent formation of cyclic 3'-5'-guanosine monophosphate. In the kidney, activation of the endothelial L-arginine pathway is associated with increases in renal blood flow, diuresis and natriuresis, while the glomerular filtration rate remains constant. The activity of the endothelial L-arginine pathway is impaired in hypertension and during chronic therapy with cyclosporine A. In addition, diabetes and atherosclerosis impair this pathway. Thus, the endothelial L-arginine pathway plays an important role in the local regulation of blood flow. Alterations in the activity of this pathway may play an important role in the pathophysiology of hypertension and renal disease.
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PMID:The endothelial L-arginine/nitric oxide pathway and the renal circulation. 175 83


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