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)

Renal prostaglandins (PGs) help maintain renal blood flow and glomerular filtration rate when the kidney is exposed to a vasoconstrictor stress. In addition, they aid pressure natriuresis and blunt the antidiuretic effect of vasopressin. Angiotensin-converting enzyme (ACE) inhibitors could decrease renal PG synthesis by reducing angiotensin II (Ang II) formation or increase it by preventing kinin inactivation. Additionally, they could affect PG synthesis or catabolism directly. The effects of ACE inhibitors on blood pressure and renal hemodynamics appear to be largely independent of changes in renal PG synthesis. Similarly, there is no evidence that pressure natriuresis is modified by ACE inhibitors. A kinin induced increase in collecting duct PG synthesis may account for the water diuresis seen clinically with ACE inhibitors. A possible beneficial interaction between thromboxane synthesis inhibitors and ACE inhibitors may exist. Thromboxane synthetase inhibitors can reduce renal vascular resistance by redirecting PG endoperoxide synthesis toward prostacyclin. This effect may be offset by a prostaglandin-induced increase in renin release and Ang II formation. ACE inhibitors, by preventing Ang II synthesis, may increase the vasodilation due to thromboxane synthesis inhibition.
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PMID:Renal prostaglandin synthesis and angiotensin-converting enzyme inhibition. 138 64

The antihypertensive effect of inhibitors of the angiotensin I-converting enzyme (ACE = kininase II) results from their vasodilatory and natriuretic effects as well as their effect on baroreceptor function. In addition to the inhibition of systemic and local angiotensin II formation, other local hormonal systems may also be involved in this effect at multiple target sites. Thus, potentiation of the vasodilator and natriuretic kinin system following inhibition of kininase II is thought to contribute to the persistent hypotensive effect of ACE inhibitors despite normalization of circulating ACE activity. Although increased plasma bradykinin levels cannot be detected, we found that the enhanced kinin-dependent local vascular prostacyclin production can be blunted in vitro by aprotinin, a kallikrein inhibitor. ACE inhibition may affect the atrial natriuretic peptide (ANP) system as the renin-angiotensin system and ANP appear to play antagonistic roles at the peripheral and central nervous system levels. Inhibition of kallikrein or of kininase II were both shown to modulate the natriuretic and vasorelaxant effects of ANP. In hypertensive subjects, we found that ACE inhibition with blood pressure normalization reduces basal and stimulated plasma ANP and blunts the renal sodium excretion in response to saline loading. In contrast, we did not observe effects of acute ACE inhibition in healthy sodium-depleted volunteers on plasma vasopressin under basal conditions or in response to passive tilt. Finally, we investigated the interaction of ACE inhibition with substance P, a powerful endogenous diuretic and natriuretic peptide that may have a transmitter function in the baroreceptor reflex arch.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinin- and non-kinin-mediated interactions of converting enzyme inhibitors with vasoactive hormones. 169 69

The mechanisms by which captopril inhibits vasopressin-stimulated osmotic water flow in the toad bladder have been investigated in vitro. Captopril has two possible mechanisms for the inhibitory action on the water flow, one is its stimulative effect on prostaglandin E2 (PGE2) biosynthesis by inhibition of kininase II activity, the other, is a direct effect on water flow independent of PGE2. Captopril inhibited the vasopressin-, cyclic adenosine monophosphate- and 3-isobutyl-1-methyl-xanthine-stimulated water flow. The inhibition of water flow by bradykinin was enhanced by captopril. These data indicate that captopril increased the amount of bradykinin in toad bladder cells resulting in the production of PGE2 which inhibited the increase in water flow induced by vasopressin. The inhibitory effect of captopril, however, also occurred in the presence of indomethacin, when the production of PGE2 was attenuated. Thus, it was concluded that captopril inhibits the vasopressin-stimulated water flow indirectly by inhibiting the degradation of bradykinin and thereby enhancing the production of PGE2, and directly at a site following the production of cyclic adenosine monophosphate by vasopressin.
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PMID:Mechanisms for the inhibition of vasopressin-stimulated water flow by captopril in the toad bladder. 244 80

The major complication of extracorporeal membrane oxygenation (ECMO) for the treatment of neonatal respiratory failure is bleeding related to heparinization. Systolic hypertension has emerged as another serious side effect in our experience. Thirty-eight of the first 41 newborns we treated with ECMO developed a systolic blood pressure greater than 90 mm Hg. The mean hypertension index (HI blood = hours greater than 90/hr on ECMO) was 0.17 +/- 0.16. Possible biochemical mediators were assayed in 17 patients. Plasma renin activity (PRA), aldosterone, epinephrine, norepinephrine, prostaglandin E2, thromboxane, and antidiuretic hormone were elevated. Angiotensin-converting enzyme (ACE) and prostacyclin were not elevated. Eighteen patients (44%) had intracranial hemorrhage (ICH), and 11 patients (27%) had clinically significant ICH. The HI was significantly (p less than 0.005) lower in those patients without ICH (0.11 +/- 0.01) than in those patients with ICH (0.25 +/- 0.04). PRA at hour 12, day 2, and day 3 was significantly higher (p less than 0.05) in patients experiencing ICH (62 +/- 42; 93 +/- 15; 73 +/- 30 ng/ml/hr) than in those without ICH (27 +/- 25; 14 +/- 8; 12 +/- 4 ng/ml/hr). An aggressive approach to medical management evolved that included hydralazine, nitroglycerine, and captopril, which protected against ICH. Two of 23 patients (9%) treated with the protocol sufferred clinically significant ICH, whereas nine of 18 patients (50%) treated before implementation of the protocol experienced ICH. The ACE inhibitor captopril was most effective in the control of hypertension. We conclude that systolic hypertension is common during neonatal ECMO, is associated with ICH, and is related to a high PRA. Aggressive management of hypertension during ECMO can reduce the incidence of ICH, and captopril is an important component of this aggressive medical management.
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PMID:Hypertension during extracorporeal membrane oxygenation: cause, effect, and management. 282 41

Captopril (CA), a specific inhibitor of kininase II, did not alter osmotic water permeability (Posm) when present in the mucosal bath of the urinary bladder isolated from the toad Bufo arenarum at a concentration of 2.3 X 10(-3) M. This treatment, however, caused a 65% enhancement in the increase in Posm following serosal exposure to vasopressin, oxytocin or theophylline, agents that increase intracellular cyclic AMP levels. The effect of captopril was prevented by procedures that reduce the kallikrein (KK)-like alkaline esterase activity present in the bladder (such as simultaneous exposure to 2.3 X 10(-5) M aprotinin, or pretreatment of the toads with 0.1 N NaCl for several days before the experiment) or by replacing the mucosal bath with fresh solution of identical composition after exposure to captopril. In contrast, changing the serosal bath did not alter the effect of the drug. These results are consistent with an effect of CA at a step beyond cAMP generation, and suggest it is mediated by release of a soluble factor, probably a kinin, into the mucosal bath. These observations, together with data previously published, suggest that the KK-kinin system may participate in the control of epithelial water and electrolyte permeability in the toad bladder. In particular, under environmental stress, it may become important in the regulation of the animal's extracellular fluid volume, thus exhibiting an adaptive value.
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PMID:A role for the kallikrein-kinin system in the regulation of osmotic water permeability in the toad bladder. 287 44

The evidence presented here suggests strongly that the kallikreins-kininogens-kinins-kininase II system has most significant role in regulation of systemic BP. This system is involved in mediation and modulation of renin-angiotensin-aldosterone, PGS and vasopressin in the regulation of sodium water balance, renal hemodynamic and BP. Therefore, reduction in the kinin-formation due to high production of kininase II, and lower formation of tissue kallikrein might result in an increased release of vasoconstrictor angiotensin II on one side, and on the other side much reduced production of PGE, vasodilator. These changes might lead to deranged vascular smooth muscle structures and cell membrane functions, retention of sodium and water, increased plasma volume, and renovascular constriction. These physiological defects might result in the development of essential hypertension (Fig. 4). Although, it is possible now to treat hypertensive conditions with tissue kallikrein and kininase II inhibitors. These discoveries have opened up new vistas to research on the pharmacological applications of kallikreins-kininogens-kinins-kininases in human diseases.
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PMID:Interrelationship between the kallikrein-kinin system and hypertension: a review. 328 Mar 99

Congestive heart failure is a complex clinical syndrome characterized by a number of neuroendocrine responses. These responses are probably an evolutionary vestige of mechanisms designed to defend volume and maintain circulatory homeostasis. Activation of the sympathetic nervous system and renin-angiotensin-aldosterone system and the release of vasopressin have been clearly documented in patients with heart failure. Unlike the normal ventricle, the failing ventricle responds to peripheral vasoconstriction and sodium retention with further hemodynamic embarrassment and circulatory congestion. Certain vasorelaxant natriuretic substances are also released during heart failure, perhaps in an attempt to offset excessive peripheral constriction and sodium retention. Prostaglandin E2, atrial natriuretic peptide (or atrial natriuretic factor) and plasma dopamine are found to be increased in some patients with heart failure. However, peripheral constriction and sodium retention appear to be dominant, particularly in the advanced stages of heart failure. An understanding of these neuroendocrine responses has led to new developments in therapy. Angiotensin-converting enzyme inhibitors have emerged as distinctly useful drugs in the treatment of heart failure. Agents designed to block excessive sympathetic drive and inhibit vasopressin are under investigation. Infusion of atrial natriuretic factors and the use of selective dopamine agonists are also undergoing clinical trials in patients with heart failure. Increased knowledge of the neuroendocrine responses will likely result in even newer and more imaginative therapy.
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PMID:Neuroendocrine manifestations of congestive heart failure. 329 96

This study investigates the endogenous kallikrein-kinin system's role as a modulator of vasopressin action in the toad urinary bladder. Kalli-krein inhibition by aprotinin, which results in decreased kinin production, significantly increased both vasopressin and 8-Br-cyclic (c) AMP-stimulated water flow. Kinin potentiation by the kininase II inhibitor captopril (SQ 14225) significantly decreased vasopressin and 8-Br-cAMP-stimulated water flow. In contrast to water flow, vasopressin-stimulated urea permeability was decreased by aprotinin and increased by captopril. We conclude that the endogenous kallikrein-kinin system represents a significant modulator of vasopressin action and it permits separate control of vasopressin-stimulated water flow and solute transport.
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PMID:Role of the endogenous kallikrein-kinin system in modulating vasopressin-stimulated water flow and urea permeability in the toad urinary bladder. 616 39

It has become increasingly clear that the potent vasoactive peptides bradykinin and angiotensin share a common point of metabolism, i.e., angiotensin-converting enzyme or kininase II, and may interact with prostaglandins to regulate regional blood flow. To establish whether the sensitivity to exogenous bradykinin was affected by the presence of angiotensin, vasodepressor dose-response curves to injected bradykinin were performed in conscious rats before and during a 1-h infusion of angiotensin I (30 ng/min), angiotensin II (30 and 300 mg/min), and [Sar2,Ala8]angiotensin II (5 micrograms/min). All of these induced a parallel leftward shift of the bradykinin dose-response curve of approximately threefold. No similar changes were observed during control infusions of dextrose, similar pressor doses of lysine vasopressin, or norepinephrine. Sensitivity to bradykinin was enhanced by saralasin in normal and nephrectomized rats, suggesting that the antagonist itself was responsible. Similar potentiation was present during both acute (1 h) and chronic infusions (9 days) of angiotensin II and attenuated the effect of a converting-enzyme inhibitor on bradykinin sensitivity. Accordingly, these results suggest a competitive interaction in vivo between angiotensin congeners and bradykinin at a point of bradykinin degradation, probably angiotensin-converting enzyme or kininase II. This is a potential additional mechanism by which these systems may interact to affect regional blood flow and must be considered in the interpretation of results obtained during saralasin infusion.
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PMID:Evidence for bradykinin potentiation by angiotensin congeners in conscious rats. 625 51

The activity of the angiotensin-converting enzyme (ACE) (kininase II, EC 3.4.15.1) was examined in 5 discrete hypothalamic nuclei of rats lacking vasopressin (homozygous Brattleboro rats, DI, di/di) and their corresponding controls (heterozygous Brattleboro rats, HZ, di/+, and Long Evans, LE, +/+ rats), with and without hormonal replacement with arginine-vasopressin (AVP). DI rats showed a vasopressin-reversible increased ACE activity when compared with LE controls, HZ rats showing intermediate activity. These changes occurred only in the supraoptic and periventricular hypothalamic nuclei, and were absent in other hypothalamic areas studied, including the paraventricular nucleus. These results provide biochemical evidence in support of previous anatomical and physiological data, for an interaction between the brain vasopressin and angiotensin systems in discrete hypothalamic nuclei, and suggest that vasopressin could regulate the formation of brain angiotensin II by modulating the activity of the converting enzyme.
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PMID:Vasopressin-reversible increase in angiotensin-converting enzyme in specific hypothalamic nuclei of Brattleboro rats. 628 72


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