Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

1. The effects on blood pressure and on pressor responses to noradrenaline (NA), of NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine methyl ester (L-NAME), inhibitors of the L-arginine/nitric oxide pathway, were investigated in anaesthetized rats receiving an infusion of bacterial endotoxin (E. coli lipopolysaccharide, LPS). 2. Infusion of LPS (10 mg kg-1 h-1) for 50 min had no effect on mean arterial blood pressure (MABP) but induced a reduction in responsiveness to noradrenaline (100 ng-1 micrograms kg-1). L-NMMA (30 mg kg-1), but not D-NMMA, caused an increase in MABP of approximately 30 mmHg and restored responses to NA. This effect was reversed by L- but not D-arginine (100 mg kg-1). 3. In LPS-treated rats, blood pressure responses to NA were only marginally increased by the cyclooxygenase inhibitor, indomethacin (5 mg kg-1). L-NAME (1 mg kg-1) caused a similar increase in MABP and restored pressor responses to NA both in the presence and absence of indomethacin. 4. Co-infusion of vasopressin (100 ng kg-1, for 10 min) with LPS (10 mg kg-1 h-1) in order to reproduce the hypertensive effect of L-NMMA and L-NAME increased pressor responsiveness to 100 and 300 ng kg-1 NA but not to 1 microgram kg-1 NA. 5. Infusion of sodium nitroprusside (30 micrograms kg-1 min-1) decreased responsiveness to NA even when the hypotension was corrected by co-infusion of vasopressin (50 ng kg-1 min-1). 6. These results demonstrate that the restoration of vascular responsiveness to NA in LPS-treated anaesthetized rats by inhibitors of the L-arginine/nitric oxide pathway is stereospecific and reversible. Furthermore, the experiments involving indomethacin suggest that although cyclo-oxygenase products of arachidonic acid may contribute to the development of LPS-induced hyporeactivity, the effect of L-NAME is unlikely to involve inhibition of the cyclo-oxygenase pathway. Comparison of NA responsiveness during vasopressin and L-NMMA/L-NAME-induced hypertension shows that increasing the blood pressure may modify LPS-induced hyporeactivity, but cannot account for the complete restoration of responses to NA by L-NMMA and L-NAME. These observations suggest that activation of nitric oxide formation from L-arginine makes a direct contribution to the production of vascular hyporeactivity by LPS in vivo.
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PMID:The effect of inhibitors of the L-arginine/nitric oxide pathway on endotoxin-induced loss of vascular responsiveness in anaesthetized rats. 190 34

Homozygous Brattleboro (i.e. vasopressin-deficient) rats were chronically instrumented with pulsed Doppler probes and intravascular catheters to permit continuous monitoring of regional haemodynamics. Over a 9 h period, rats drinking water showed no systematic changes in heart rate or mean arterial blood pressure although renal, mesenteric and hindquarters vascular conductances fell. These changes showed diurnal rhythms, probably related to the nocturnal habits of rats. In separate groups of animals spontaneous oral ingestion of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) or NG-nitro-L-arginine methyl ester (L-NAME; 0.1 mg ml-1) caused marked hypertension but no significant bradycardia. Compared to control animals, rats drinking L-NMMA for 9 h showed significantly greater mesenteric and hindquarters vasoconstrictions, and rats drinking L-NAME showed greater vasoconstrictions in all 3 vascular beds.
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PMID:Regional haemodynamic changes during oral ingestion of NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester in conscious Brattleboro rats. 228 51

The aim of the present study was to investigate the effects of long-term blockade of nitric oxide synthesis with the L-arginine analogue N omega-nitro-L-arginine methyl ester (L-NAME) for 8 weeks on coronary vascular and myocardial structural changes. Four groups of Wistar-Kyoto rats were studied: those with no treatment, those treated with L-NAME 1 g/L (3.7 mmol/L in drinking water), those treated with L-NAME 0.1 g/L (0.37 mmol/L in drinking water), and those treated with L-NAME 1.0 g/L and hydralazine 120 mg/L (0.6 mmol/L in drinking water). After 8 weeks, the heart was excised, and the degrees of structural changes in coronary arteries (wall-to-lumen ratio and perivascular fibrosis), myocardial fibrosis, and myocyte size were quantified by an image analyzer. Chronic inhibition of nitric oxide synthesis increased arterial pressure compared with control animals. Chronic inhibition of nitric oxide synthesis caused significant microvascular remodeling (increased wall-to-lumen ratio and perivascular fibrosis). Cardiac hypertrophy was also observed after chronic inhibition of nitric oxide synthesis. Coadministration of hydralazine prevented arterial hypertension but did not affect microvascular remodeling and cardiac hypertrophy induced by the chronic inhibition of nitric oxide synthesis. In addition, chronic inhibition of nitric oxide synthesis caused scattered lesions of myocardial fibrosis, which was significantly attenuated by cotreatment with hydralazine. These results suggest that long-term blockade of nitric oxide synthesis caused coronary microvascular remodeling and cardiac hypertrophy in rats in vivo by a mechanism other than arterial hypertension. In contrast, arterial hypertension contributed to the development of myocardial fibrosis induced by long-term blockade of nitric oxide synthesis.
Hypertension 1995 Dec
PMID:Chronic inhibition of nitric oxide synthesis causes coronary microvascular remodeling in rats. 749 Jan 55

The chronic inhibition of NO-synthase by NG-nitro-L-arginine methyl ester (L-NAME, a L-arginine analogue) induces a dose-dependent decrease in aortic cGMP and an increase in blood pressure. We used this pharmacological approach to evaluate the release of NO in vivo in spontaneously hypertensive rats (SHR); 15 SHR and 10 Wistar-Kyoto rats (WKY) were given 25 mg L-NAME/kg/d by gavage for 15 days; 10 SHR and 10 WKY rats given water for the same period were used as control. During the trial, 10/15 SHR given L-NAME died. Systolic blood pressure (mmHg) increased from 132 +/- 6 to 170 +/- 4 in WKY given L-NAME and from 169 +/- 4 to 242 +/- 6 in SHR given L-NAME. Aortic cGMP content (fmol/mg protein) was 2,204 +/- 382 and 2,076 +/- 461 fmol/mg control WKY and SHR (NS), and was decreased to 324 +/- 44 and 641 +/- 70 in WKY and SHR given L-NAME respectively (p < 0.0001 each). L-NAME increased plasma atrial natriuretic factor only in SHR. In summary, basal aortic cGMP content, reflecting the basal release of NO, was similar in WKY and SHR. The decrease in aortic cGMP content of SHR given L-NAME, due to the blockade of NO-synthase, was accompanied by a large increase in systolic blood pressure and a tremendous mortality rate. Thus, basal release of NO is probably not impaired in SHR, but represents a major counterregulatory mechanism in this genetic model of arterial hypertension.
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PMID:[Vasodilator effect of nitric oxide is a necessary counter-regulation in the spontaneously hypertensive rat]. 751 Apr 67

The influence of dietary sodium restriction and angiotensin II blockade on hypertension induced by a 25-day period of administration of the inhibitor of nitric oxide synthesis NG-nitro-L-arginine methyl ester (L-NAME: 10 mg/kg twice daily by gavage) was assessed in Wistar rats fed a normal or low sodium diet. In addition, the angiotension II receptor blocker, losartan (30 mg/kg once daily by gavage) was administered prior to and during L-NAME in rats fed the normal sodium diet. Results expressed as mean +/- ESM are presented in the following table: [table: see text] At the end of studies, conscious systolic arterial pressure increased similarly in L-NAME-treated groups maintained on NS or LS intake. Moreover, a 25% reduction in cardiac output due to a decrease in stroke volume was observed in both groups. A slight but significant cardiac hypertrophic response was observed in hypertensive rats irrespective of sodium intake. Losartan totally prevented the development of hypertension as well as the decrease in cardiac output and the cardiac hypertrophy associated with L-NAME treatment in rats on normal sodium intake. In conclusion, hypertension resulting from chronic blockade of nitric oxide synthesis was not affected by dietary sodium restriction. A crucial role for the renin-angiotensin system was demonstrated in this new model of hypertension.
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PMID:[Sodium intake and angiotensin in hypertension induced by chronic NO synthase inhibition in the rat]. 751 Apr 68

The effects of N omega-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase (1,5, and 10 mg/kg) on vasopressor and depressor responses to segmental sympathetic nerve stimulation were studied in the pithed rat preparation. Vasopressor responses were evoked by stimulation of the spinal sympathetic outflow at T6-T8 (30 V, 0.05 ms at 5 Hz with 10 pulses). This pressor response was biphasic: An initial transient response (to nerve stimulation) was followed by a later prolonged response (to adrenal catecholamine release). L-NAME 1, 5, and 10 mg/kg increased mean arterial blood pressure (MAP); this effect was maximal at 1 mg/kg L-NAME, but had no effect on heart rate (HR). L-NAME 1, 5, and 10 mg/kg potentiated both phases of the pressor response; the effect was maximal at 10 mg/kg. Vasodepressor responses were evoked by stimulation of the spinal sympathetic outflow at S2-L6 (30 V, 0.05 ms at 5 Hz with 10 pulses). L-NAME 1, 5, and 10 mg/kg did not inhibit these depressor responses. We conclude that inhibition of the synthesis of endogenous NO causes a hypertension in pithed rats that is associated with increased vasoconstriction in response to sympathetic nerve stimulation and adrenal catecholamine release. Systemic vascular depressor responses to segmental sympathetic nerve stimulation are not affected, however; therefore, NO cannot be the major mediator of these responses.
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PMID:Endogenous nitric oxide modulates vasopressor responses, but not depressor responses, to spinal sympathetic nerve stimulation in pithed rats. 751 64

We examined the effect of non-antihypertensive doses of the angiotensin-converting enzyme inhibitor ramipril, kinins, and/or nitric oxide on left ventricular hypertrophy in rats with aortic coarctation. We investigated the effect of either HOE 140, a specific B2 receptor antagonist, or NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on the antihypertrophic effect of ramipril at non-antihypertensive doses (10 micrograms/kg per day) failed to alter left ventricular hypertrophy significantly, although a small decrease was obtained. Given at a dose of 1 mg/kg per day for 6 weeks, ramipril prevented increased blood pressure and left ventricular hypertrophy after aortic coarctation. Neither of these effects was blocked by simultaneous administration of HOE 140 (500 micrograms/kg per day). In rats with aortic coarctation treated with L-NAME, blood pressure increased further but left ventricular weight did not. Ramipril (1 mg/kg per day) significantly reduced left ventricular hypertrophy, although blood pressure was still higher than in rats given water alone. The slope of the correlation between left ventricular weight and blood pressure in rats that received L-NAME was significantly lower than in rats that did not (0.52 versus 1.29; P = .008). This suggests that for each 1 mm Hg that the blood pressure increased, the increase in left ventricular weight was less in the L-NAME groups. Thus, only antihypertensive doses of ramipril possessed antihypertrophic activity. Kinins did not participate in the chronic antihypertensive and antihypertrophic effects of ramipril. In hypertension induced or aggravated by chronic nitric oxide synthase, L-NAME partially impaired development of left ventricular hypertrophy for reasons that are unclear.
Hypertension 1994 Jun
PMID:Role of kinins and nitric oxide in the antihypertrophic effect of ramipril. 751 54

The goal of the present study was to evaluate the effect of long-term nitric oxide synthase inhibition by NG-nitro-L-arginine-methyl ester (L-NAME) on the morphology and viscoelastic properties of the carotid arteries in rats. Twelve-week-old Wistar-Kyoto rats were treated for 6 weeks with either the nitric oxide synthase inhibitor L-NAME (0.4 g/L in drinking water; L-NAME rats, n = 13) or tap water (control rats, n = 13). Age-matched spontaneously hypertensive rats (SHR, n = 14) received tap water for the same period. The internal diameter of the common carotid artery was measured continuously with an echo-tracking device with the rats under anesthesia with halothane. Intra-arterial pressure was monitored on the contralateral side. L-NAME rats exhibited arterial pressures similar to those of SHR. The distensibility pressure-curve determined in L-NAME rats was a direct continuation of that obtained in control rats. In contrast the distensibility in SHR was increased (P < .01, SHR versus L-NAME rats). Carotid artery cross-sectional area and left ventricular weight index were increased similarly in SHR and L-NAME rats compared with control rats. Thus the hypertension caused by long-term nitric oxide synthesis inhibition was not associated with the increased arterial distensibility observed in SHR despite similar blood pressure elevations, similar arterial hypertrophy, and consequently similar wall stress. This suggests a role for nitric oxide in regulating the mechanical behavior of arteries exposed to high blood pressure.
Hypertension 1994 Jun
PMID:Long-term nitric oxide synthase inhibition and distensibility of carotid artery in intact rats. 751 55

Nitric oxide (NO) has effects on renal blood flow, glomerular filtration rate, renin secretion, and renal sodium excretion. Four isoforms of nitric oxide synthase (NOS) have been cloned to date. However, the molecular identity of NOS present in the renal vasculature is unknown. Endothelial NOS (NOS-III) is regulated both acutely by cell calcium and chronically by shear stress. To determine if renal blood vessels and the glomerulus express NOS-III mRNA, we used degenerate polymerase chain reaction (PCR) to clone a portion of rat NOS-III. We then assayed NOS-III mRNA in microdissected renal structures by reverse transcriptase-PCR. NOS-III mRNA was expressed at high levels in glomeruli, arcuate vessels, and interlobular artery/afferent arterioles. NOS-III mRNA was detected inconsistently in proximal tubules, thick ascending limbs, and cortical and inner medullary collecting ducts. Previous studies have shown that chronic oral treatment with the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) decreases NO synthesis and causes hypertension. To determine if the systemic blockade occurs only by competitive inhibition, we determined the effect of L-NAME on glomerular NOS-III mRNA. L-NAME administration (5 days) decreased NOS-III mRNA in the glomerulus to 25 +/- 12% of control levels. We conclude that endothelial NOS-III mRNA is preferentially expressed in the glomerulus and renal vasculature, where it can modulate renal blood flow and glomerular filtration rate. Furthermore, glomerular NOS-III may be modulated at the level of mRNA abundance in vivo by systemic L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Localization and regulation of endothelial NO synthase mRNA expression in rat kidney. 752 Jun 68


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