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

The effect of oral supplementation of L-arginine, the substrate of nitric oxide, (1.25 g/liter water) and captopril (15 mg/liter water) was studied in 5/6 nephrectomized rats for a period of three months. N-omega-nitro L-arginine, a nitric oxide synthase inhibitor, was given orally (70 mg/liter water) with or without L-arginine or captopril. The urinary excretion of nitrite (NO2) + nitrate (NO3), the known metabolites of nitric oxide, was taken as an index of nitric oxide production. Chronic renal failure rats were characterized by a low creatinine clearance, high FENa%, proteinuria, hypertension and a low urinary excretion of NO2 + NO3; 0.152 +/- 0.06 (P < 0.001) nmol/micrograms creatinine compared with 0.481 +/- 0.004 (P < 0.001) in normal rats and 0.479 +/- 0.11 (P < 0.001) in untreated sham-operated rats. Both L-arginine and captopril were effective in the normalization of all these parameters. The combination of L-arginine and captopril had no additive effects. The nitric oxide synthase inhibitor significantly diminished the captopril beneficial effect. It is concluded that chronic renal failure in rats is a low nitric oxide production state. The supplementation of L-arginine is shown to overcome this condition. It is suggested that the beneficial effect of captopril on chronic renal failure is through a specific L-arginine--nitric oxide synthase--nitric oxide pathway.
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PMID:Oral administration of L-arginine and captopril in rats prevents chronic renal failure by nitric oxide production. 764 19

We tested the hypotheses that maintaining the activity of nitric oxide by L-arginine infusion would counteract the release of an endogenous nitric oxide synthase inhibitor, improve survival, and decrease intraoperative hypertension after infrarenal aortic cross-clamp surgery. Hindlimb ischemia was generated by infrarenal aortic cross-clamping and tying of the left femoral artery for 5 hours in rats with bilateral femoral and sciatic nerves cut. Mean blood pressure significantly increased during the 5-hour ischemic period in ischemic rats (no drug treatment). Baroreceptor function was inhibited in ischemic rats assessed by intravenous dose response to phenylephrine and nitroprusside after 5 hours of ischemia, suggesting baroreceptor resetting. In ischemic rats infused with L-arginine the intraoperative hypertension was prevented during the 5-hour period, suggesting that this hypertension may be mediated by nitric oxide inhibition. The rates of survival and arrhythmias 2 hours after declamping were 50% in ischemic rats and 100% in ischemic rats treated with N omega-nitro-L-arginine (a nitric oxide synthase inhibitor) 10 minutes before declamping. In ischemic rats infused with L-arginine the survival rate was significantly increased to 100% and the arrhythmic rate was inhibited. We conclude that L-arginine prevents hypertension during cross-clamping and decreases the mortality rate and arrhythmias after declamping by maintaining nitric oxide synthesis. These results suggest that humoral factors released from the ischemic hindlimb may inhibit endogenous nitric oxide production, thus contributing to intraoperative hypertension, arrhythmias, and high mortality rate after aortic cross-clamp surgery.
Hypertension 1995 Sep
PMID:Stimulation of endogenous nitric oxide pathway by L-arginine reduces declamp mortality and attenuates hypertension associated with aortic cross-clamp-induced hindlimb ischemia in rats. 764 74

This study aimed to determine the mechanism of hypertension associated with nitric oxide synthase inhibition. Intravenous injections of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, produced a sustained increase in systemic blood pressure and a decrease in heart rate in anesthetized dogs, whereas NG-nitro-D-arginine had no effect. L-Arginine reversed the pressor response. NG-Nitro-L-arginine-induced hypertension was markedly attenuated or abolished by treatment with hexamethonium; this inhibition was still observed when the blood pressure fall caused by the ganglionic blocking agent was compensated by continuous infusion of angiotensin II. In dogs treated with phentolamine in a dose sufficient to lower blood pressure to the level similar to that elicited by hexamethonium and to suppress the pressor response to norepinephrine, the hypertensive effect of NG-nitro-L-arginine was not attenuated. We conclude that hypertension caused by the nitric oxide synthase inhibitor is associated with an elimination of nitroxidergic neural function rather than an impairment of the basal release of nitric oxide from the endothelium.
Hypertension 1993 Jan
PMID:Neural mechanism of hypertension by nitric oxide synthase inhibitor in dogs. 767 95

The sphincter of Oddi has basal myogenic phasic activity that is modulated by neural and hormonal pathways. Stimulatory innervation to this organ is cholinergic, whereas the inhibitory pathways are unknown. Nitric oxide (NO), generated from L-arginine, relaxes gastrointestinal smooth muscle in vitro. We, therefore, hypothesized that resting sphincter of Oddi and duodenal motilities are regulated by a NO-mediated inhibitory pathway. In 23 anesthetized prairie dogs, systemic blood pressure and sphincter of Oddi and duodenal motilities were monitored during systemic infusion of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. L-NAME was infused alone and simultaneously with excess D- and L-arginine. L-NAME alone and L-NAME with D-arginine produced hypertension and increased sphincter of Oddi and duodenal motilities. L-arginine blocked these increases, suggesting that baseline sphincter of Oddi and duodenal motility regulation involves the generation of NO from L-arginine. We conclude that baseline sphincter of Oddi phasic activity is regulated by cholinergic stimulatory and NO-mediated inhibitory neural pathways.
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PMID:Nitric oxide inhibits resting sphincter of Oddi activity. 767 90

To determine whether inhibition of generation of endothelium-derived relaxing factor or nitric oxide (NO) resulted in elevated blood pressure and its effect on resistance arteries, rats were offered NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase, in their drinking water. Blood pressure (BP) rose slightly from 100 +/- 2 mmHg in controls to 130 +/- 5 mmHg with 25 mg/Kg L-NAME per day and to 173 +/- 9 mmHg with 100 mg/Kg per day for 2 1/2 to 4 weeks. Rats were studied after 1-2 weeks of hypertension (BP > 150 mmHg). The concentration of cyclic guanosine monophosphate, the intracellular second messenger of NO, was significantly depressed in aorta and in the mesenteric vascular bed in L-NAME-treated rats. Mesenteric resistance arteries studied on a wire-myograph exhibited similar external and lumen diameters, whereas media width and media/lumen ratio were greater (p < 0.01). Cross-sectional area of the media was similar. Active wall tension in response to norepinephrine tended to be greater in blood vessels from L-NAME-treated rats, while responses to vasopressin and endothelin-1 were unaltered. Sensitivity to norepinephrine was significantly enhanced in L-NAME-treated rats (p < 0.001), while that to endothelin-1 and arginine8 vasopressin was similar. In conclusion, administration of an NO synthase inhibitor produces hypertension, with exaggerated media/lumen ratio in resistance arteries and enhancement of response to norepinephrine, which together with decreased NO generation may contribute to elevation of blood pressure.
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PMID:Effect of hypertension induced by nitric oxide synthase inhibition on structure and function of resistance arteries in the rat. 768 50

Blockade of the renin-angiotensin system was studied in male Sprague-Dawley rats during long-term inhibition of nitric oxide synthase. Nitro-L-arginine-methyl ester (L-NAME) was placed in the drinking water for 4 weeks (approximately 100 mg/kg per day). Separate groups of rats were coadministered the angiotensin II antagonist A-81988 in the drinking water ranging from approximately 0.001 to 1 mg/kg per day. Control groups received only tap water or A-81988 alone. Each week, rats were placed in metabolic cages, and tail-cuff blood pressures and blood samples were taken. L-NAME produced a sustained elevation in tail-cuff pressure that was completely prevented by A-81988. No changes in creatinine clearance, sodium excretion, plasma creatinine concentration, or blood urea nitrogen were observed. Food and water intakes were identical in all groups. Water excretion was significantly increased in L-NAME-treated animals regardless of additional inhibitor treatment, suggesting a possible role for nitric oxide synthase in the control of water excretion; this effect was independent of blood pressure. Although less potent than A-81988, the angiotensin II antagonist losartan and the angiotensin converting enzyme inhibitor enalapril also blocked L-NAME-induced hypertension. In a separate series of experiments, rats were not given A-81988 until 2 weeks after hypertension had fully developed in L-NAME-treated rats. Within 1 week of treatment with the angiotensin II antagonist, tail-cuff pressure returned to normal. We conclude from these studies that long-term inhibition of endogenous nitric oxide production produces an angiotensin II-dependent form of hypertension.
Hypertension 1993 May
PMID:Angiotensin blockade reverses hypertension during long-term nitric oxide synthase inhibition. 768 26

Chronic ethanol consumption is associated with an increased prevalence of hypertension. The mechanisms of this form of hypertension are unknown. Rats fed ethanol for 2 days develop a tolerance to the acute vasoconstrictive effects of ethanol that is believed to be endothelium dependent. We investigated the effects of acute and chronic ethanol exposure on agonist-stimulated nitric oxide synthase activity in bovine pulmonary artery endothelial cells. Exposure of bovine pulmonary artery endothelial cells to ethanol (100 mmol/L) for 20-120 minutes did not change either basal or agonist-stimulated nitric oxide synthase activity measured as the rate of conversion of [3H]L-arginine to [3H]L-citrulline. Chronic exposure of endothelial cells to ethanol (100 mmol/L) for 96 hours significantly increased bradykinin-, adenosine 5'-triphosphate-, and ionomycin-stimulated nitric oxide synthase activity without affecting basal enzyme activity. The ethanol-induced increase in nitric oxide synthase response to agonists was dependent on the duration of ethanol exposure as well as the concentration of ethanol. Moreover, the effect of ethanol was characterized by an increase in the maximal nitric oxide synthase response to adenosine 5'-triphosphate without changes in the EC50. Removal of calcium or addition of N omega-nitro-L-arginine completely abolished agonist-stimulated nitric oxide synthase activity in both control and ethanol-treated cells. Our observations support the hypothesis that ethanol enhances nitric oxide synthase response to agonists during early ethanol exposure and may serve in a protective role against its hypertensive effect.
Hypertension 1993 Jun
PMID:Ethanol enhances the endothelial nitric oxide synthase response to agonists. 768 6

To elucidate whether cytokines induce nitric oxide synthase in vascular smooth muscle cells, we studied the effects of human recombinant interleukin-1 beta on the synthesis and release of nitric oxide in cultured rat vascular smooth muscle cells by measurement of NO2-/NO3- levels. Furthermore, we performed Northern blot analysis using subcloned polymerase chain reaction products as probes for constitutive and inducible nitric oxide synthase. Interleukin-1 beta dose dependently (1 to 20 ng/mL) stimulated NO2-/NO3- production as a function of time. Northern blotting demonstrated the interleukin-1 beta-induced expression of messenger RNA for an inducible but not for the constitutive nitric oxide synthase after 3 hours. NG-Monomethyl L-arginine completely blocked the interleukin-1 beta-induced NO2-/NO3- production, the effect of which was reversed by L-arginine but not by D-arginine. Dexamethasone inhibited the interleukin-1 beta-induced NO2-/NO3- production in a dose-dependent manner (10(-9) to 10(-7) M) and the interleukin-1 beta-inducible nitric oxide synthase messenger RNA levels. Neither a calmodulin inhibitor (W-7) nor a protein kinase C inhibitor (staurosporine) showed any effects on the induction of nitric oxide synthase transcripts or production of NO2-/NO3- stimulated by interleukin-1 beta, whereas cycloheximide and actinomycin D completely inhibited the basal and stimulated NO2-/NO3- production. These data demonstrate for the first time that interleukin-1 beta induces gene expression of inducible nitric oxide synthase and its de novo protein synthesis in rat vascular smooth muscle cells, thereby leading to generation of nitric oxide via Ca2+/calmodulin-independent and protein kinase C-independent mechanisms.
Hypertension 1993 Jul
PMID:Induction of nitric oxide synthase gene by interleukin in vascular smooth muscle cells. 768 32

A porphyrinic sensor was used to monitor nitric oxide released from cultured endothelial and vascular smooth muscle cells obtained from genetically hypertensive rats and from a normotensive reference strain of rats. Endothelial cell nitric oxide synthase (the constitutive enzyme) was stimulated with bradykinin, and vascular smooth muscle cell nitric oxide synthase (the inducible enzyme) was induced with interleukin-1 beta. Both types of cells from hypertensive rats released less nitric oxide than did cells from normotensive rats. The observed deficient nitric oxide release from endothelial and smooth muscle cells may contribute to the elevated vascular tone and increased cell growth described in hypertension.
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PMID:Nitric oxide synthase activity in genetic hypertension. 768 19

Nitric oxide is synthesised from an amino acid, L-arginine, by a family of enzymes called nitric oxide (NO) synthase, by most cells in the vessel wall. In healthy vessels, the production of NO is due to the constitutive and calcium dependent NO synthase present in the endothelial cells. On the other hand, when the vascular system is diseased and defense mechanisms are activated, the mediators of inflammatory and immunitary reactions induce an NO synthase non-responsive to calcium which produces large quantities of NO in most of the cells of the vessel wall. Nitric oxide is a liposoluble radical with a short half-life. It plays a central role in the regulation of the motricity and proliferation of blood vessels and in the interaction of the blood cells with the vessel wall. An inadequate production of nitric oxide could play a role in many vascular diseases such as hypertension, atherosclerosis, restenosis or vascular hyporeactivity associated with septicaemic shock.
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PMID:[Nitric oxide and homeostasis of the smooth vascular muscle]. 769 33


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