UMLS:C0020538 - FACTA Search

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

To determine whether an angiotensin II receptor antagonist (AT antagonist) could improve the impaired coronary circulation as well as induce regression of cardiac hypertrophy in the hypertensive heart, and to elucidate whether the nitric oxide system in the coronary artery was involved in this mechanism, the AT1 antagonist, TCV-116 (10 mg/kg), was administered orally to spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY), and coronary flow was measured in the isolated hearts. High systolic blood pressure in SHR was significantly reduced by a 2-week treatment with TCV. Left ventricular (LV) hypertrophy in SHR regressed after TCV treatment, while LV weight in WKY was not reduced. Total minimum coronary vascular resistance (MCVR) obtained with adenosine (10(-5) M) infusions in a Langendorff apparatus was significantly greater in SHR than in WKY. Increased MCVR in SHR was reduced after TCV treatment. Coronary perfusion with NG-monomethyl-L-arginine monoacetate (L-NMMA) increased coronary vascular resistance (CVR) in WKY, while it failed to increase CVR in SHR. TCV treatment restored the responses to L-NMMA in SHR. These findings suggest that the AT1 antagonist, TCV-116, lowered the high blood pressure in SHR, concomitantly improving the impaired coronary circulation, and that it induced regression of the cardiac hypertrophy. The suppressed nitric oxide (NO) system in the coronary vessels in SHR appeared to be activated by TCV treatment.
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PMID:Effect of an angiotensin II receptor antagonist, TCV-116, on cardiac hypertrophy and coronary circulation in spontaneously hypertensive rats. 788 11

To clarify the role of endogenous angiotensin II (AngII) in the hypertension of spontaneously hypertensive rats (SHR), we examined the chronic effects of central and systemic administration of losartan, an angiotensin AT1 receptor antagonist, on blood pressure and arterial baroreceptor reflex. The SHR and Wistar-Kyoto rats (WKY), aged 12 to 16 weeks, received subcutaneous infusions of losartan at a dose of 10 mg/kg/day, or intracerebroventricular infusions of losartan at doses of 1 or 10 mg/kg/day for 14 days. Control groups received either isotonic saline solution subcutaneously or intracerebroventricular artificial cerebrospinal fluid. On day 14, baroreflex control of heart rate was determined by intravenous phenylephrine, and pressor response to intravenous AngII (100 ng/kg) was investigated in conscious rats. Blood pressure was higher and the sensitivity of the baroreflex control of heart rate was lower in vehicle-treated SHR than in WKY. Chronic subcutaneous administration of losartan lowered the blood pressure throughout the infusion period in both SHR and WKY, but the hypotensive effects were significantly greater in SHR. Losartan also sensitized the impaired baroreflex in SHR. Chronic intracerebroventricular losartan at a dose of 1 mg/kg/day did not alter the blood pressure or the baroreflex control of the heart rate in either strain. The effects of 10 mg/kg/day of intracerebroventricular losartan on blood pressure and the baroreflex were similar to those of the same dose administered subcutaneously. The pressor response to intravenous AngII was similarly inhibited by intracerebroventricular and subcutaneous losartan doses of 10 mg/kg/day.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic effects of central and systemic administration of losartan on blood pressure and baroreceptor reflex in spontaneously hypertensive rats. 791 52

In the present study we used radiotelemetry technology to investigate: 1) the time course for development of hypertension in 2-kidney, 1-clip (2K1C) rats and 2) the effect of chronic caffeine consumption on blood pressure in 2K1C rats. Rats received water or caffeine (0.1%) in drinking water and were instrumented with radiotelemetry devices to permit continuous monitoring of blood pressure. A clip was placed on the left renal artery of rats in both the water (WATER/CLIP) and caffeine (CAFFEINE/CLIP) groups. The clip was applied briefly to, then removed from, the renal artery of caffeine- and water-treated rats randomized to the sham-operated (SHAM) group. Mean arterial blood pressure (MABP) increased by approximately 35 mm Hg within 2 hr of clipping. MABP in the WATER/CLIP and CAFFEINE/CLIP groups differed significantly from the SHAM group, but not from each other, for the first 10 days after clipping. Thereafter, MABP was greater in the CAFFEINE/CLIP rats as compared to WATER/CLIP rats. At 4.5 weeks after clipping, MABP values differed significantly in the CAFFEINE/CLIP, WATER/CLIP and SHAM rats (140 +/- 4, 122 +/- 4 and 103 +/- 2 mm Hg, respectively). Involvement of the renin-angiotensin system was assessed by treatment with the AT1 receptor antagonist, losartan, and the converting enzyme inhibitor, captopril. Results from this study indicate: 1) hypertension develops rapidly after clipping in rats monitored with telemetry; 2) the renin-angiotensin system is involved in maintaining hypertension in 2K1C rats even beyond 4 weeks after clipping; and 3) caffeine augments the increase of blood pressure in 2K1C rats, apparently through the involvement of the renin-angiotensin system.
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PMID:Telemetric blood pressure monitoring in benign 2-kidney, 1-clip renovascular hypertension: effect of chronic caffeine ingestion. 793 54

There is increasing evidence that an activated intrarenal renin-angiotensin system (RAS) alters renal hemodynamics and fluid balance and that such events may lead to the development of hypertension. To examine the role of the glomerular RAS in the development of hypertension in the spontaneously hypertensive (SHR) rat, we studied angiotensin (ANG) II receptors in isolated glomeruli from young (4- to 5-wk-old) and adult (10- to 12-wk-old) SHR and from age-matched, normotensive Wistar-Kyoto (WKY) rats. Glomerular ANG II receptor density in young SHR is 3-fold higher than in age-matched WKY rats (2033 +/- 154 versus 742 +/- 151 receptors/microns2; p < 0.05) and 1.5-fold higher than in adult SHR and WKY rats (1128 +/- 85 and 1198 +/- 181 receptors/microns2, respectively; p < 0.05). Additional studies demonstrated that the differences in receptor density are not related to disparity in receptor occupancy and that they are also independent of systemic ANG levels. Suppression of RAS by ANG converting enzyme inhibitors resulted in a 3-fold increase in receptor density in young SHR rats and a 4.5-fold increase in young WKY rats; receptor density remained greater in young SHR rats (5915 +/- 318 versus 3358 +/- 234 receptors/microns2, p < 0.05). Furthermore, competitive binding experiments using the nonpeptide ANG II antagonists losartan (AT1) and PD 123319 (AT2) indicate that the greater ANG II receptor density in the young SHR rats represents an increase in the number of a single population of AT1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glomerular losartan (DuP 753)-sensitive angiotensin II receptor density is increased in young spontaneously hypertensive rats. 793 16

The conscious spontaneously hypertensive rat (SHR), compared to its normotensive control Wistar Kyoto rat (WKY), exhibited a significantly greater pressor response to i.v. angiotensin II and angiotensin III. Losartan (10 mg/kg i.v.) lowered the basal blood pressure of the SHR but had no significant effect on that of the WKY. However, it attenuated the pressor response to both angiotensins in the SHR and WKY, the degree of attenuation being significantly greater with angiotensin III. In addition, the pressor responses induced by both angiotensin II and angiotensin III in the WKY, compared to those of the SHR, were more markedly inhibited by losartan. The results indicate a possible over-expression of angiotensin AT1 receptors in the SHR, and that both angiotensin II and angiotensin III contribute to the hypertension by acting on these receptors.
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PMID:Enhanced pressor response to angiotensin III in spontaneously hypertensive rats: effects of losartan. 795 99

This study investigated the ability of the selective angiotensin II (AII)-type (AT)1 receptor antagonist losartan to reverse the fast (< 30 sec) pressor effect of AII, and the hypertension produced by chronic (2 weeks) i.v. infusion of AII (AII hypertension). We hypothesized the following: if AII hypertension is caused solely by stimulation of AT1 receptors mediating the fast pressor effect, then the time course of the antihypertensive effect of losartan in AII hypertension should parallel the time course of losartan inhibition of pressor responses to acute, bolus injection of AII. Thus, in one group of rats, pressor responses to bolus injections of AII (10 ng, n = 10) were measured before and subsequently at numerous time points after losartan administration (3 mg.kg-1 i.v.). Other groups of rats received continuous infusions of AII i.v. for 15 days at 2 ng.min-1 (n = 8), 4 ng.min-1 (n = 8) or 10 ng.min-1 (n = 6). On days 2, 7 and 12 of the AII infusion, rats received a bolus injection of losartan (3 mg.kg-1, i.a.). Mean arterial pressure (MAP) was then measured at numerous time points after losartan administration. Within 5 min of administration, losartan caused almost complete inhibition of fast pressor responses to acute injections of AII, and the magnitude of this inhibition did not change for over 24 hr. On the other hand, in AII hypertension, losartan lowered MAP significantly within 5 min only in rats receiving 10 ng.min-1 AII, but in all three groups caused a slower decline in MAP that peaked around 2 hr after losartan injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Time course of losartan blockade of angiotensin II hypertension versus blockade of angiotensin II fast pressor effects. 796 99

The central effect of angiotensin II on cardiovascular activity has been investigated in conscious trout bearing an intracerebroventricular (i.c.v.) cannula and an intra-arterial catheter. I.c.v. injection of the angiotensin II agonist [Asn1,Val5]AII (6.2-50 pmol) induced a dose-dependent increase in heart rate and arterial blood pressure. Central administration of the angiotensin II antagonist DuP 753 (5 nmol) 30 min before i.c.v. injection of [Asn1,Val5]AII totally prevented the tachycardia and reduced the hypertension induced by the angiotensin II agonist. Intra-arterial injection of arginine-vasotocin (12.5 pmol) caused a bradycardia associated with a marked increase in arterial blood pressure. I.c.v. injection of [Asn1,Val5]AII totally blocked the bradycardia induced by arginine-vasotocin and this effect was prevented by central administration of DuP 753. In contrast, [Asn1,Val5]AII did not affect the increase in blood pressure induced by arginine vasotocin. Suppression of the vagal tone by atropine treatment totally blocked the central effect of [Asn1,Val5]AII. These results show that angiotensin II acts directly on the trout brain to increase blood pressure and heart rate. The effect of angiotensin II is mediated through a receptor related to the mammalian AT1 receptor type.
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PMID:Intracerebroventricular administration of angiotensin II increases heart rate in the conscious trout. 798 71

1. The effect of GR117289, an angiotensin AT1 receptor antagonist, on diastolic blood pressure (DBP) was determined in angiotensin-dependent and angiotensin-independent models of hypertension in rats. In addition, the antagonist profile of GR117289 at angiotensin AT1 receptors was determined in conscious renal hypertensive rats and conscious normotensive rats, dogs and marmosets. 2. Intra-arterial and oral administration of GR117289 (0.3-3 mg kg-1, i.a.; 1-10 mg kg-1, p.o.) to 6-day left renal artery ligated hypertensive (RALH) rats (DBP > 140 mmHg) produced significant, dose-related reductions in DBP with little apparent effect on heart rate (< 15%). The antihypertensive effect of GR117289 developed progressively over several hours and with some doses persisted for 24-48 h after administration. 3. Administration of GR117289 (1 mg kg-1, i.a.) on 5 consecutive days to RALH rats reduced DBP on each day. The antihypertensive effect of GR117289 was not cumulative as DBP had almost returned to base-line values, 24 h after administration of each dose. 4. A dose of GR117289 (3 mg kg-1, i.a.), which produced a substantial reduction in DBP (about 70 mmHg) in RALH rats, was administered to rats in which blood pressure was elevated either by unilateral renal artery clipping, sustained infusion of angiotensin II (AII), DOCA-salt administration or genetic inbreeding. GR117289 reduced DBP in rats in which the renin-angiotensin system was activated by renal artery clipping or AII infusion but had little effect in normotensive rats, DOCA-salt rats and SHR. 5. Systemic administration of All to RALH rats and to normotensive rats, dogs and marmosets elicited reproducible pressor responses in all species. Systemic or oral administration of GR1 17289 (3 mg kg-1)inhibited the pressor responses produced by All, resulting in parallel, rightward displacements of All dose-response curves.6. Maximal displacements of All dose-response curves occurred 1 h and 1-7 h after systemic and oral administration, respectively. GR1 17289 produced a 32-246 fold displacement after systemic administration and a 4-12 fold displacement after oral administration. The effect in dogs was short lasting after systemic administration but the effect of GRI17289 lasted for up to 24 h in rats and marmosets and for up to 24 h after oral administration in all species. The antagonist activity appeared specific for angiotensin receptors as GRi17289 did not inhibit pressor responses to phenylephrine or vasopressin.7. These experiments demonstrate that GRI 17289 reduces blood pressure in conscious hypertensive rats after both systemic and oral administration, and is an effective antagonist at angiotensin AT1 receptors in conscious rats, dogs and marmosets.
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PMID:Cardiovascular effects of GR117289, a novel angiotensin AT1 receptor antagonist. 801 89

We conducted the present study to determine whether the angiotensin II type I receptor (AT1) gene might be implicated in human essential hypertension by using case-control and linkage studies. The entire coding and 3' untranslated regions of the AT1 receptor gene (2.2 kb) were amplified by polymerase chain reaction and submitted to single-strand conformation polymorphism in 60 hypertensive subjects with a familial susceptibility. We identified five polymorphisms (T573-->C, A1062-->G, A1166-->C, G1517-->T, and A1878-->G). However, no mutations that alter the encoded amino acid sequence were detected. A case-control study performed on white hypertensive (n = 206; blood pressure, 168 +/- 16/103 +/- 9 mm Hg) and normotensive (n = 298; blood pressure, 122 +/- 10/75 +/- 9 mm Hg) subjects using three of five polymorphisms showed a significant increase in allelic frequency of C1166 in hypertensive subjects (0.36 versus 0.28 for normotensive subjects, chi 2 = 6.8, P < .01). Frequencies for the alleles of the other two polymorphisms (T573-->C, A1878-->G) were similar in both groups. We performed a linkage study using the affected sib pair method and a highly polymorphic marker of the AT1 receptor gene. There was no evidence for linkage in 267 sib pairs analyzed from 138 pedigrees. These findings would be compatible with a common variant of the AT1 receptor imparting a small effect on blood pressure; further studies will be needed to address this possibility.
Hypertension 1994 Jul
PMID:Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. 802 Oct 9

Carbohydrate enriched diets have been shown to elevate blood pressure in the rat. The precise mechanism by which carbohydrate feeding elevates blood pressure is not known. We evaluated the role of the renin-angiotensin system in the etiology of fructose-induced hypertension. Losartan potassium, an angiotensin II (AII) Type 1 (AT1) receptor antagonist, was utilized to assess the blood pressure response to fructose treatment. Male Sprague-Dawley rats were divided into 3 groups. Rats in the control group were fed regular chow. The other two groups were fed 60% fructose diet for 4 weeks. One of these groups was chronically treated with losartan potassium in drinking water. Throughout the study there was no significant difference in body weight between the three groups. There was a significant increase in blood pressure of fructose-treated rats within one week of treatment which remained elevated for the remainder of the study. Chronic losartan treatment significantly attenuated the rise in blood pressure. Within two weeks both the dipsogenic response and the pressor response to AII demonstrated complete blockage of AII receptors. These results suggest that the renin-angiotensin system plays a role in the development of fructose-induced hypertension.
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PMID:Effect of chronic losartan potassium treatment on fructose-induced hypertension. 804 Dec 26

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