Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Potassium depletion causes hypotension in normotensive animals and can lower the blood pressure in hypertensive animals and humans. Potential mechanisms for this hypotensive effect include a decrease in aldosterone levels, a decrease in vasopressin, and decreased responsiveness to the pressor effects of angiotensin II. The decreased response to angiotensin II could result from increased prostaglandin production, receptor occupancy, or a decrease in angiotensin II receptor affinity. A high potassium intake has no effect on blood pressure in normotensive animals and humans, but lowers blood pressure in those with hypertension. Mechanisms for this antihypertensive effect include natriuresis with sodium depletion, a decrease in plasma renin activity, an alteration in the neurogenic components of blood pressure regulation, and effects on resistance vessels related either to a high potassium concentration or to a decrease in the number of angiotensin II receptors.
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PMID:Effects of potassium on blood pressure control. 634 96

Mildly dehydrated conscious Merino ewes were infused with vasopressin (AVP) at 5 mu x min-1 alone and simultaneously with the angiotensin II receptor blocker sar1ala8-angiotensin II (saralasin) at 15 micrograms x min-1. AVP was slightly pressor and produced an increase in the calculated total peripheral resistance, and an increase in glomerular filtration rate, urine flow and electrolyte excretion, without a change in total renal plasma flow. These results indicate renal efferent arteriolar vasoconstriction as well as other non-renal vasoconstriction. Saralasin infusion checked the rise in total peripheral resistance (which continued to increase after saralasin withdrawal), but caused a marked increase in renal vascular resistance resulting in a decrease in renal plasma flow and to a lesser extent in glomerular filtration rate. These results suggest that saralasin was acting as an angiotensin II agonist in the kidney, but as an antagonist elsewhere. Deductions from previous experiments in the literature of the renal function of angiotensin II, based on its supposed inhibition by saralasin, may not be justified.
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PMID:The effects of sar1ala8-angiotensin II in vasopressin-treated dehydrated sheep. 685 46

Experiments were carried out in male Sprague-Dawley rats. 3'-end digoxigenin-labeled 26 bp oligonucliotide probe was used to detect the vasopressin (AVP) mRNA in the hypothalamus. Dot blotting technique was used in the investigation of AVP gene transcription level. The results showed that continuous intracerebroventricular administration (i.c.v.) of angiotensin II at a rate of 0.2 nmol/h for 2 days by using a miniosmotic pump resulted in a significant increase in daily water intake. An increase of AVP gene transcription level in the hypothalamus was also observed, but statistically insignificant. When daily water intake was limited (25 ml/d), continuous i.c.v. infusion of ANG II caused a significant increase in hypothalamic AVP gene transcription. It was also observed that hypothalamic AVP gene transcription level increased after salt loading and dehydration. However, intraperitoneal application of angiotensin converting enzyme inhibitor captopril (5 mg/(kg.d)) or i.c.v. nonpeptide angiotensin II receptor antagonist Dup753 (0.9 nmol/h) did not attenuate the increase of AVP gene transcription level induced by salt loading or dehydration. It is therefore suggested that the administration of ANG II enhances AVP gene transcription in the hypothalamus, especially when water intake is limited. However, this increase does not involve the participation of endogenous ANG II.
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PMID:[Effect of angiotensin II on vasopressin gene transcription in the hypothalamus of rats]. 748 79

The effects of the nonpeptide angiotensin II receptor antagonist losartan and the angiotensin-converting enzyme inhibitor captopril on pressor responses to the selective alpha 1-adrenoceptor agonist cirazoline (10 ng/kg-3.0 mg/kg) in the pithed rat were compared. In addition, the effects of losartan and captopril on pressor responses to cirazoline were compared in the presence of the selective irreversible alpha 1-adrenoceptor antagonist SZL-49 (1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-bicyclo[2,2,2]octa-2,5- dienyl-carbonyl)-piperzine) and/or the Ca2+ channel antagonist nifedipine. Losartan (5.0 mg/kg) and captopril (3.0 mg/kg), as compared to saline, significantly lowered the blood pressure of intact, anaesthetized and pithed rats. Continuous infusion with vasopressin was used to restore the blood pressure of pithed rats pretreated with losartan or captopril to a level comparable to animals that had received saline. Losartan, captopril, nifedipine (1.0 mg/kg), and SZL-49 (10.0 mg/kg) antagonized the pressor actions of cirazoline, which displaced the dose-diastolic blood pressure response curve for the agonist to the right. Moreover, pressor responses to cirazoline were significantly reduced in rats that had received losartan and nifedipine in comparison to nifedipine alone. In contrast, in rats treated with nifedipine, further administration of captopril did not significantly reduce pressor responses to cirazoline as compared to nifedipine alone. Cirazoline-mediated pressor responses at all doses were significantly attenuated in rats treated with SZL-49 and either losartan or nifedipine combined as compared to SZL-49 alone. In contrast, only cirazoline-mediated pressor responses at lower doses were significantly reduced by pretreatment with a combination of SZL-49 and captopril as compared to SZL-49 alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of losartan and captopril on vasopressor actions of cirazoline in the absence and presence of SZL-49 and nifedipine. 756 55

The growing list of vasoactive substances known to be involved in blood pressure control provides new targets for antihypertensive drugs. Currently under development are alternative strategies for blockade of the renin-angiotensin system (e.g., renin inhibition and angiotensin II receptor antagonism) that may have fewer side effects than angiotensin-converting-enzyme inhibition, and antagonists to other vasocontrictor peptides, such as endothelin and vasopressin. Novel strategies to enhance the effects of endogenous vasodilators, such as natriuretic peptides and nitric oxide, are also being explored.
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PMID:Beyond ACE inhibition: new developments in drug therapy for hypertension. 760 80

The pressure-natriuresis curve of transgenic rats harboring an extra mouse renin gene [TGR(mRen-2)27] is shifted rightward compared with controls; however, whether intrarenal angiotensin II effects are responsible for the rightward shift is unknown. To clarify this issue we infused the converting enzyme inhibitor captopril or the angiotensin II receptor blocker CV 11974 into transgenic and normotensive Sprague-Dawley Hannover control rats. We eliminated any other neural or endocrine regulatory differences between transgenic and control rats by renal denervation and infusion of vasopressin, aldosterone, corticosterone, and norepinephrine in sufficient quantities to occupy all receptors. Sodium excretion increased from 3.4 +/- 1.2 to 10.1 +/- 0.5 mumol/min per gram kidney weight in transgenic rats when renal perfusion pressure was increased from 158 to 201 mm Hg. Captopril (4 mg/kg) and CV 11974 (0.1 mg/kg) shifted the pressure-natriuresis curve of transgenic rats leftward, so that sodium excretion was threefold higher at similar renal perfusion pressures (150 to 160 mm Hg). Similarly, fractional sodium and water excretion curves were shifted leftward, so that values for transgenic and control rats were no longer different. Over the pressure range, renal blood flow in transgenic rats ranged from 3.1 +/- 0.7 to 4.4 +/- 0.5 mL/min per gram kidney weight and increased (P < .05) with both captopril and CV 11974 to ranges from 4.8 +/- 0.9 to 6.8 +/- 0.6 or from 4.5 +/- 0.7 to 6.9 +/- 1.0 mL/min per gram kidney weight, respectively. Glomerular filtration rate in transgenic rats, on the other hand, was not increased. Transgenic kidneys showed severe hypertension-induced nephrosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of captopril and angiotensin II receptor blockade on pressure natriuresis in transgenic TGR(mRen-2)27 rats. 764 84

Although prevention of heart failure recently has become a realistic issue, management of heart failure once the syndrome has developed, is mainly supportive, based on the various cardiac and peripheral changes which occur in the course of heart failure. Of these, abnormal neurohormonal activation is of major pathophysiologic and prognostic significance. Consequently, modulation of neuroendocrine activation is now recognized a prime target in the treatment of heart failure, besides diuretic therapy. In this respect, the value of converting enzyme inhibition is well established. Future developments in this area include dopaminergic agents, vasopressin antagonists, angiotensin II receptor antagonists, renin inhibitors, spironolactone and, possibly, ANF peptidase inhibitors. Besides diuretics, necessary when signs of fluid retention are present, the approach to heart failure management involves other pharmacologic issues. In view of abnormal vascular control with vasoconstriction prevailing during progressive heart failure, it clearly makes sense to vasodilate. However, of available vasodilators, only the combination of relatively high dose nitrates and hydralazine has proven to be of clinical significance, in terms of hemodynamics, exercise capacity and survival. It is possible, though, that novel generation dihydropyridine derivatives may prove beneficial as well. Thus far, there has been much debate concerning the usefulness and particularly the safety of positive inotrope therapy and inodilator treatment. Taken together, this concern relates to presence and predominance of cAMP-dependent mechanisms to induce these effects. Thus, sympathomimetic agents and phosphodiesterase inhibitors, such as milrinone or enoximone, are without beneficial effects, but instead shorten survival during long-term therapy. This may be different where compounds which act through cAMP-independent mechanisms, i.e., calcium sensitization or sodium channel stimulation, are concerned, but needs to be confirmed yet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Congestive heart failure. Drug therapy: central or peripheral approach? 791 52

Losartan, a nonpeptide angiotensin II receptor antagonist, was used to establish the role of brain AT1 angiotensin II receptor subtype on the natriuretic, antidiuretic, and dipsogenic actions of centrally administered renin. Intracerebroventricular administration of renin reduces urine volume and increases sodium excretion and water intake in conscious, male, hydrated rats. Losartan (3 or 10 mg/kg, sc) reduced the increased sodium excretion and totally inhibited the antidiuretic action induced by intracerebroventricular renin. When both renin and Losartan were given intracerebroventricularly, at the highest dose, there was a potent inhibition of the antidiuretic and natriuretic actions. Peripheral and central administration of the AT1 receptor blocker significantly lengthened the onset of drinking behavior and reduced the cumulative water intake observed after intracerebroventricular injection of renin. Our results strongly suggest that the brain AT1 receptor subtype mediates the physiologic actions of angiotensin II, such as drinking behavior, the increase in sodium excretion, and vasopressin release.
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PMID:Effect of Losartan, a nonpeptide angiotensin II receptor antagonist, on drinking behavior and renal actions of centrally administered renin. 845 3

UP 269-6, 5-methyl-7-propyl-8(-)[2'-(1H-tetrazol-5-yl)biphenyl-4- yl)methyl]-1,2,4-triazolo]1,5-c]pyrimidin-2(3H)-one is a novel nonpeptide angiotensin II receptor antagonist. In vivo studies were performed to evaluate UP 269-6 for its angiotensin II antagonistic action. In pithed rats, i.v. administration of UP 269-6 (0.03-1 mg/kg) shifted dose dependently to the right the dose-pressor response curve for angiotensin II and decreased the maximum response. The angiotensin II antagonistic effect of UP 269-6 was as potent as that of L-158,809 (5,7-dimethyl-2-ethyl-3(-)[[2'- (1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-imidazo[4,5-b]pyridine) and 10 times more potent than that of losartan. UP 269-6 antagonized the angiotensin II sympathetic-mediated tachycardiac response. UP 269-6 inhibited dose dependently the pressor response to angiotensin II with an ID50 of 4.5 micrograms/kg, i.v. in conscious normotensive dogs. Oral administration of UP 269-6 (0.1 to 30 mg/kg) resulted in a dose-dependent and long-lasting inhibition of the angiotensin II-induced pressor response in conscious normotensive rats and dogs. Compared to losartan, UP 269-6 presented a more rapid onset of action. UP 269-6 caused similar angiotensin II antagonistic effects in rats and dogs but the duration of the effect was greater in dogs than in rats. UP 269-6 did not alter the tachycardiac response to isoproterenol and the pressor response to vasopressin. UP 269-6 was demonstrated to be devoid of agonistic properties in rats and dogs. Furthermore, UP 269-6 did not induce hypotension and did not cause alteration in heart rate and ECG waveforms in dogs even at a dose 1000 times higher than the angiotensin II antagonistic effective dose. These results demonstrate that UP 269-6 is a potent and specific angiotensin II receptor antagonist and dose not possess agonistic properties.
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PMID:In vivo pharmacological characterization of UP 269-6, a novel nonpeptide angiotensin II receptor antagonist. 854 20

The present study investigates the effect of angiotensin II and LR-B/081 (-methyl 2-[[4-butyl-2-methyl-6-oxo-5-[[2'-(1H-tetra-zol-5-yl) [1,1'-biphenyl]-4-yl] methyl]-1(6H)-pyrimidinyl] methyl]-3-thiophenecarboxylate), a novel non-peptide angiotensin II receptor antagonist, on both early and late responses in rat vascular smooth muscle cells. Angiotensin II induced a rapid and transient elevation of inositol trisphosphate intracellular levels, triggered the release of both prostaglandin E2 and prostaglandin I2 (EC50 = 21 +/- 3 and 16 +/- 2 nM, respectively), and, in long-term studies, increased leucine and thymidine incorporation. All angiotensin II effects were antagonized by LR-B/081 and losartan, the reference non-peptide angiotensin AT1-selective receptor antagonist, whereas they were unaffected by PD123177 (1-(4-amino-3-methylphenyl)methyl-5-diphenylacetyl-4,5,6,7-tetr ahy dro-1H- imidazo[4,5-c]pyridine carboxylic acid), a non-peptide angiotensin AT2-selective receptor antagonist. LR-B/081 displayed a much higher potency than losartan in inhibiting angiotensin II-induced prostaglandin E2 (IC50 = 0.15 +/- 0.02 and 39 +/- 9 nM, respectively) and prostaglandin I2 release (IC50 = 0.18 +/- 0.04 and 134 +/- 40 nM, respectively) and was also more potent in blocking the increase in protein synthesis (IC50 = 242 +/- 119 nM and 1221 +/- 687 nM, respectively). Moreover, LR-B/081 and losartan blocked the response to angiotensin III but failed to inhibit the prostaglandin release stimulated by vasopressin or the mitogenic effect of serum. LR-B/081 and losartan were devoid of intrinsic properties in the experimental conditions employed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin II-induced responses in vascular smooth muscle cells: inhibition by non-peptide receptor antagonists. 856 96


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