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

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

Nephrotoxicity caused by cyclosporin A (CSA) is the result of vasoconstriction of the renal microcirculation. The endothelium-derived relaxing factor nitric oxide (NO) regulates microvascular blood flow in various tissues, and mediates the microcirculatory response during hypertension and sepsis. This study investigated the role of NO in CSA-induced renal vasoconstriction. Hydronephrotic kidneys in rats were suspended in an environmentally controlled tissue bath, and interlobular, afferent and efferent arteriolar diameters and blood flow were measured by in vivo videomicroscopy. CSA was administered alone, with the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) or with exogenous NOS substrate L-arginine. CSA significantly constricted the whole of the renal microvasculature whereas L-NAME alone preferentially constricted the preglomerular vessels. L-Arginine reversed the vasoconstriction induced by CSA whereas L-NAME had no further effect. Preglomerular basal vascular tone is dependent on continuous production of NO and alterations in the L-arginine-NO pathway contribute to CSA-induced renal vasoconstriction.
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PMID:An experimental study of altered nitric oxide metabolism as a mechanism of cyclosporin-induced renal vasoconstriction. 774 87

NG-nitro-L-arginine methyl ester (L-NAME) and 11-desoxycorticosterone plus salt intake (DOCA-salt) hypertensive rat models were compared to study the possible involvement of model-specific factors in the development of renal angiopathy and left ventricular hypertrophy (LVH). Blood pressure was measured in L-NAME, DOCA-salt hypertensive, and control Wistar rats, and the lesions of nephroangiosclerosis and left ventricular hypertrophy were evaluated after 7 weeks. Arterial wall cyclic guanosine monophosphate, plasma renin activity (PRA), and renal renin storage were assessed in parallel. For the same level of hypertension in the two models, the renal arterial fibrinoid necrotic lesions were significantly more frequent in L-NAME than in DOCA-salt hypertensive rats. In DOCA-salt hypertensive rats, PRA was decreased and arterial cGMP increased compared to controls. In the L-NAME model, arterial cGMP decreased and PRA showed a bimodal distribution in this intermediate stage of hypertensive disease. LVH was observed in DOCA-salt rats and only in the L-NAME rats with a high level of PRA. There was a close correlation between the lesions of nephroangiosclerosis, left ventricular index, and plasma renin activity in L-NAME rats. We therefore suggest that the activation of the renin-angiotensin system participates specifically in the development of the second stage of hypertension during chronic blockade of NO synthase involving nephroangiosclerosis and LVH.
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PMID:Renal hypertensive angiopathy. Comparison between chronic NO suppression and DOCA-salt intoxication. 775 45

The effect of chronic intravenous infusion of the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 8.6 mg.kg-1.day-1) on blood pressure, intrarenal blood flow distribution, and sodium and water balance was studied in conscious rats. On the 1st day of intravenous L-NAME infusion, renal medullary blood flow was reduced by 22%, renal cortical blood flow was unaltered, approximately 1 meq of sodium and 12 ml of water were retained, and blood pressure increased from 96 +/- 2 to 118 +/- 2 mmHg. Medullary blood flow was maintained at this decreased level, sodium continued to be retained, body weight continued to increase, and blood pressure remained elevated for the 5 days of L-NAME infusion. During the postcontrol period, blood flow in the renal medulla returned to levels not significantly different from control; the animals went into negative sodium balance and stopped gaining weight, and blood pressure returned to control. The present experiments indicate that decreased renal medullary blood flow and retention of sodium and water play an important role in the development of hypertension during chronic systemic L-NAME administration despite no measurable changes in renal cortical blood flow.
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PMID:Role of renal medullary blood flow in the development of L-NAME hypertension in rats. 786 23

This study examined whether nitric oxide synthesis blockade or potentiation (with N omega-nitro-L-arginine methyl ester [L-NAME] or N-acetylcysteine, respectively) can shift the relations between sodium excretion, papillary blood flow, and renal perfusion pressure. Papillary blood flow was measured by laser Doppler flowmetry. A low dose of L-NAME (3.7 nmol/kg per minute) reduced papillary blood flow only at high arterial pressure (140 mm Hg), but it had no effect on pressure natriuresis. Infusion of 37 nmol/kg per minute L-NAME reduced cortical blood flow by 9% at all perfusion pressures studied, lowered papillary blood flow by 8% and 19% at 120 and 140 mm Hg, respectively, and blunted the pressure-natriuresis response. The administration of 185 nmol/kg per minute L-NAME reduced cortical blood flow by 30% and decreased papillary blood flow by 25% in the range of 100 to 140 mm Hg of arterial pressure. Blockade of nitric oxide synthesis with L-NAME at all doses studied reduced papillary blood flow only at high renal perfusion pressures, but papillary blood flow remained essentially unchanged at low perfusion pressures, thus restoring papillary blood flow autoregulation. N-Acetyl-cysteine (1.8 mmol/kg) increased papillary blood flow by 9% and shifted the relations between papillary blood flow, sodium excretion, and renal perfusion pressure toward lower pressures. This effect of N-acetylcysteine on papillary blood flow was blocked by subsequent L-NAME administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Mar
PMID:Role of nitric oxide on papillary blood flow and pressure natriuresis. 787 67

Endothelium-derived nitric oxide (EDNO) and angiotensin II play a role in the regulation of vascular tone and sodium handling. The objective of this study was to determine the role played by angiotensin II in mediating the arterial pressure and renal response to increments in sodium intake during chronic EDNO inhibition. Six groups of Wistar rats were studied; they were fed either a normal sodium diet (groups I, II, and III) or a high sodium diet (groups IV, V and VI). Rats in groups II, III, V and VI were placed on oral L-N-nitroarginine-methyl ester (L-NAME) for 4 weeks. In groups III and VI, the angiotensin II receptor antagonist, TCV-116, was administered. A significant increase in blood pressure was observed in group V compared with group II at the end of the experimental period. TCV-116 attenuated the L-NAME-induced hypertension in both group III and group VI. Urinary protein excretion and the glomerular sclerotic injury score in group V were greater than in group II. TCV-116 attenuated the proteinuria and glomerular injury induced by chronic EDNO inhibition in the groups with normal (group III) and high sodium intake (group IV). Systemic hypertension and glomerular injury were enhanced by salt loading during EDNO inhibition, and the angiotensin II receptor antagonist, TCV-116, attenuated this salt-induced increase in blood pressure and renal injury, suggesting that EDNO may counteract the renal effects of angiotensin II.
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PMID:Enhancement of hypertension and renal injury by salt-loading during chronic nitric oxide inhibition. Effects of TCV-116, a novel angiotensin II receptor antagonist. 788 7

Injection of N omega-nitro-L-arginine methyl ester (L-NAME), an L-arginine analogue and a potent inhibitor of nitric oxide (NO) synthase, in dorsolateral periaqueductal gray (PAG) area of freely moving rats at doses from 0.1 to 1 mumol per rat, dose-dependently increased arterial blood pressure (BP). Endothelin-1 (ET-1) injected in the same area at doses from 0.1 to 1 pmol per rat also induced pressor effects. Administration of L-NAME (1 mumol per rat) in the PAG area 10 min before ET-1 significantly (p < 0.01) potentiated ET-1-induced hypertension. Pretreatment with L-arginine (1 mumol per rat), precursor of NO, significantly (p < 0.01) decreased L-NAME-induced potentiation of ET-1 pressor effects. L-Arginine also prevented the ET-induced increase in arterial BP and reversed L-NAME-induced hypertensive effect. Prazosin and propranolol, adrenergic blocking agents, and reserpine, a depletor of catecholamine stores, reduced either ET-1 or L-NAME pressor effects. Our data suggest the presence of NO synthase in the PAG area, considered an important cerebral area in coordinating physiologic responses such as cardiovascular and respiratory adjustment. Moreover, our results suggest that even at the PAG area level, functional antagonism exists between NO and ET-1, possibly contributing, through sympathetic outflow, to central regulation of arterial BP.
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PMID:Relation between L-arginine-nitric oxide pathway and endothelin-1 effects in periaqueductal gray area of rats. 789 82

The present study was designed to investigate the role of the autonomic nervous system in experimental hypertension induced by chronic administration of N-nitro-L-arginine methyl ester (L-NAME) in the drinking water (1 mg/mL) over 6 days. L-NAME ingestion caused a large rise in resting mean arterial pressure (MAP) (175 +/- 5 mm Hg) and heart rate (HR) (440 +/- 17 beats per minute) compared to nontreated control rats (resting MAP: 112 +/- 2 mm Hg and HR: 345 +/- 8 beats per minute). Ganglionic blockade induced by trimethaphan (5 mg/kg, intravenously) caused a significantly (P < .01) greater decrease in MAP (delta -86 +/- 7 mm Hg) compared to control rats MAP (delta -44 +/- 4 mm Hg). This strongly suggests that the level of central sympathetic tone in L-NAME-treated rats is much greater than in nontreated rats. Using atenolol and atropine alone and combined, the level of resting sympathetic drive to the heart was found to be significantly increased in L-NAME-treated rats compared to control rats. However, vagal tone to the heart was found to be virtually abolished in L-NAME-treated rats compared to control rats. These results indicate that an increase in central sympathetic drive plays an important role in the hypertension induced by chronic inhibition of nitric oxide synthesis with L-NAME.
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PMID:Evidence that the autonomic nervous system plays a major role in the L-NAME-induced hypertension in conscious rats. 790 20

The objective of this study was to determine whether vasodilator effects of nitric oxide (NO) can be explained by the inhibition of vasoconstriction caused by peripheral sympathetic nerve activity (SNA) in vivo. For this purpose, we studied the effects of systemic inhibition of NO synthesis during experimental variation of SNA in anesthetized cats. Intravenous infusion of NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) in baroreceptor-intact animals (n = 6) caused increases in mean arterial blood pressure (MAP) from 105.8 +/- 3.4 to 192.0 +/- 4.3 mm Hg that were associated with slight decreases in preganglionic SNA recorded from the white ramus of the third thoracic segment. Higher SNA appeared in completely baroreceptor-denervated cats (n = 10) than in the intact cats, but no changes in nerve activity occurred after the subsequent administration of L-NAME. In contrast, MAP increased from 123.3 +/- 4.0 to 245.8 +/- 5.1 mm Hg. In baroreceptor-denervated cats, reversible suppression of peripheral SNA produced by cooling of the ventral surface of the rostral ventrolateral medulla oblongata (RVLM) caused significant hypotension (61.1 +/- 2.6 mm Hg) and almost completely reversed the hypertension caused by L-NAME (76.0 +/- 3.7 mm Hg). Intravenous administration of the alpha 1-adrenergic receptor antagonist prazosin after L-NAME reduced MAP to a similar extent. In contrast, hypertension induced by angiotensin II could not be reversed by RVLM cooling. The pressor effects of intravenously administered noradrenaline during RVLM cooling were markedly potentiated by L-NAME and attenuated by the NO-donor compound S-nitroso-N-acetylpenicillamine (SNAP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of sympathetic vasoconstriction is a major principle of vasodilation by nitric oxide in vivo. 795 45


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