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

Recent studies have indicated that acute inhibition of nitric oxide biosynthesis in the rat promotes arterial hypertension and renal vasoconstriction. We evaluated the renal and systemic effects of 4-6 weeks of nitric oxide blockade in Munich-Wistar rats receiving the nitric oxide inhibitor nitro-L-arginine orally. Age-matched untreated rats were used as controls. In an additional seven rats, nitric oxide blockade was carried out in conjunction with oral administration of the novel angiotensin II antagonist losartan potassium. Tail-cuff pressure rose progressively in nitro-L-arginine-treated rats, reaching 164 +/- 6 mm Hg at 4-6 weeks, compared with 108 +/- 3 mm Hg in controls. In rats concomitantly receiving losartan, tail-cuff pressure reached 125 +/- 6 mm Hg, still elevated compared with rats receiving losartan alone (98 +/- 3 mm Hg). Nitro-L-arginine-treated rats presented marked renal vasoconstriction and hypoperfusion, as well as a 30% fall in glomerular filtration rate and a 39% increase in filtration fraction. Treatment with Losartan normalized glomerular filtration rate, but not filtration fraction or renal vascular resistance. Plasma renin activity was elevated after nitro-L-arginine treatment. Renal histological examination revealed widespread arteriolar narrowing, focal arteriolar obliteration, and segmental fibrinoid necrosis in the glomeruli. In a separate group of rats, nitro-L-arginine administered for 1 week induced hypertension that was partially reversed by acute L-arginine, but not D-arginine or L-glycine, infusions. We conclude that chronic nitric oxide blockade may constitute a new model of severe arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Sep
PMID:Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension. 151 48

Vascular resistance is increased in the kidneys of spontaneously hypertensive rats (SHR). Previous studies have demonstrated impaired vascular relaxations of mesenteric resistance arteries of SHR because of increased production of a cyclooxygenase-dependent endothelium-derived contracting factor. To test the hypothesis that altered endothelial function contributes to the enhanced constriction in kidneys of SHR, endothelium-mediated relaxations of renal resistance arteries from 5-6-week-old prehypertensive SHR and Wistar-Kyoto rats were compared in arteriographs. Acetylcholine induced endothelium-dependent contractions in SHR arteries, while potent endothelium-dependent relaxations were noted in renal arteries from Wistar-Kyoto rats. Inhibition of cyclooxygenase (indomethacin) or blockade of prostaglandin H2-thromboxane A2 receptors (SQ 29,548) blocked acetylcholine-induced contractions in SHR renal arteries; relaxations in SHR renal arteries after either treatment were similar to those observed in renal arteries from Wistar-Kyoto rats. NG-Nitro-L-arginine inhibited acetylcholine-mediated relaxations in both SHR and Wistar-Kyoto arteries. Endothelium-independent relaxations induced by verapamil were comparable in SHR and Wistar-Kyoto arteries. Thus, the impaired response to acetylcholine in SHR renal resistance arteries may result from the release of endothelium-derived cyclooxygenase products (prostaglandin H2 or thromboxane A2), which oppose endothelium-derived nitric oxide-mediated relaxation.
Hypertension 1992 Jun
PMID:Prostaglandin H2 and thromboxane A2 are contractile factors in intrarenal arteries of spontaneously hypertensive rats. 159 83

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

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

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

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

The present investigation was undertaken to see whether a long-term inhibition of adenosine receptors--leading to hypertension--interferes with alpha 2-adrenoceptor-mediated modulation of noradrenaline release. Rat tail arteries were removed from normal and from hypertensive animals obtained by chronic treatment with intraperitoneally infused DPSPX (1,3-dipropyl-8-sulphophenylxanthine) or orally administered L-NAME (NG-Nitro-L-arginine methyl ester). To study prejunctional effects, the influence of UK-14,304 (5-bromo-6(imidazoline-2-ylamino)-quinoxaline) and yohimbine on the overflow of tritium evoked by electrical stimulation (100 V; 1 Hz; 2 ms; 5 min) from tissues preloaded with 3H-noradrenaline was analysed. To study postjunctional effects, concentration-response curves to UK-14,304 were determined. In DPSPX-treated rats there was an enhancement of the prejunctional effects of UK-14,304: its Ec30% was reduced from 381 (250; 579) to 85 (73; 99) nmol.l-1 (n = 5; P < 0.05) and its maximal effect--expressed as percent reduction of tritium overflow-increased from 45 +/- 5% to 61 +/- 5% (n = 6; P < 0.05). In L-NAME-treated rats there was no change in either of these two parameters. At the postjunctional level, there was no change in the sensitivity to UK-14,304 in tissues from either DPSPX- or L-NAME-treated rats. Yohimbine (10-1000 nmol.l-1) caused a concentration-dependent increase of tritium overflow evoked by electrical stimulation in both control and hypertensive animals (either DPSPX- or L-NAME-treated).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term administration of 1,3-dipropyl-8-sulphophenylxanthine (DPSPX) alters alpha 2-adrenoceptor-mediated effects at the pre- but not at the postjunctional level. 770 27

We tested the hypothesis that responses of the basilar artery to selective activation of endothelin-B receptors are altered during chronic hypertension. Using a cranial window in anesthetized rats, we examined responses of the basilar artery to a selective endothelin-B receptor agonist, IRL 1620, in stroke-prone spontaneously hypertensive rats (SHRSP). Under control conditions, baseline basilar artery diameter was smaller in SHRSP (196 +/- 8 microns [mean +/- SEM]) than in normotensive Wistar-Kyoto rats (WKY) (245 +/- 9 microns, P < .05). Topical application of IRL 1620 (10(-8) mol/L) dilated the basilar artery by 27 +/- 5% in WKY and 56 +/- 4% in SHRSP (P < .05). Dilatation of the basilar artery in response to sodium nitroprusside was similar in WKY and SHRSP. In contrast, acetylcholine-induced vasodilatation in SHRSP was markedly impaired. NG-Nitro-L-arginine methyl ester and NG-nitro-L-arginine, inhibitors of nitric oxide synthase, inhibited IRL 1620-induced vasodilatation in WKY. Neither NG-nitro-L-arginine methyl ester nor indomethacin attenuated vasodilatation produced by IRL 1620 in SHRSP. The major finding is that dilator responses of the basilar artery to selective activation of endothelin-B receptors are paradoxically enhanced in SHRSP compared with WKY. Dilator responses of the basilar artery to endothelin-B receptor activation are mediated by endothelium-derived relaxing factor in WKY. In contrast, responses to activation of endothelin receptors in SHRSP do not depend on the production of nitric oxide or prostanoids.
Hypertension 1995 Apr
PMID:Enhanced responses of the basilar artery to activation of endothelin-B receptors in stroke-prone spontaneously hypertensive rats. 772 88

We have reported that in two-kidney, one clip hypertensive rats, renal perfusion is maintained by a balance between the vasodilator endothelium-derived nitric oxide and the vasoconstrictor angiotensin II. Others have suggested that endothelium-derived constricting factor, reported to be thromboxane A2 and/or endoperoxide, contributes to increased blood pressure in angiotensin II-dependent hypertension. We hypothesized that in angiotensin II-dependent two-kidney, one clip hypertension, endothelium-derived constricting factor contributes to vasoconstriction of the clipped kidney following nitric oxide synthesis inhibition. Using radioactive microspheres, we studied renal blood flow to the stenotic kidney of two-kidney, one clip hypertensive rats 4 weeks after clipping. The influence of nitric oxide on systemic and renal hemodynamics was evaluated by determining the response to nitric oxide synthesis inhibition using 10 mg/kg N omega-nitro-L-arginine methyl ester in these rats, which were either not treated (n = 8) or treated (n = 8) with 4 mg/kg of the constricting factor receptor antagonist BMS 180,291. Mean basal blood pressure in rats was 167 +/- 9 mm Hg (mean +/- SEM). N omega-Nitro-L-arginine methyl ester increased blood pressure by 35 +/- 7 mm Hg (P < .001). In the clipped kidney, N omega-nitro-L-arginine methyl ester decreased renal blood flow by 40% (from 4.5 +/- 0.9 to 2.7 +/- 0.6 mL.min-1.g kidney-1; P < .01) and increased renal vascular resistance by 100% (from 51.9 +/- 9.6 to 105.0 +/- 19.2 mm Hg.mL-1.min-1.g kidney-1; P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Endothelium-derived constricting factor in renovascular hypertension. 772 35

We analyzed mechanisms underlying neurogenic vasodilatation in dog and Japanese monkey renal arteries. Isometric mechanical responses of the arterial strip to nerve stimulation by nicotine were recorded. Nicotine-induced contractions were abolished by hexamethonium and potentiated by NG-nitro-L-arginine, a nitric oxide synthase inhibitor. The potentiating effect was reversed by L-arginine. NG-Nitro-L-arginine did not potentiate the contraction caused by norepinephrine. The nicotine-induced contraction was reversed to a relaxation by prazosin. The relaxation was not influenced by indomethacin, timolol, or atropine but was abolished by NG-nitro-L-arginine, methylene blue (a guanylate cyclase inhibitor), oxyhemoglobin (a nitric oxide scavenger), and hexamethonium. In the strips treated with NG-nitro-L-arginine, the nicotine-induced relaxation was restored by L-arginine. Histochemical study demonstrated perivascular nerves containing NADPH diaphorase and nitric oxide synthase immunoreactivity in dog and monkey arteries. We conclude that renal arteries are innervated by nitric oxide-mediated vasodilator and adrenergic vasoconstrictor nerves, and depression of the vasodilator nerve function by nitric oxide synthase inhibition potentiates the contraction caused by adrenergic nerve excitation.
Hypertension 1995 May
PMID:Nitroxidergic innervation in dog and monkey renal arteries. 773 21


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