Investigação in silico de compostos naturais com potencial inibitório da enzima conversora de angiotensina I em angiotensina II / In silico investigation of natural compounds with inhibitory potential of angiotensin I-converting enzyme I in angiotensin II

The angiotensin I converting enzyme (ACE) inhibitor enalapril (MK-421), at a dose of 1 mg/kg or more by gavage twice daily, effectively inhibited the pressor response to angiotensin I for more than 12 h and less than 24 h. Plasma renin activity (PRA) did not change after 2 or 4 days of treatment at 1 mg/kg twice daily despite effective ACE inhibition, whereas it rose significantly at 10 mg/kg twice daily. Blood pressure fell significantly and heart rate increased in rats treated with 10 mg/kg of enalapril twice daily, a response which was abolished by concomitant angiotensin II infusion. However, infusion of angiotensin II did not prevent the rise in plasma renin. Enalapril treatment did not change urinary immunorcactive prostaglandin E2 (PGE2) excretion and indomethacin did not modify plasma renin activity of enalapril-treated rats. Propranolol significantly reduced the rise in plasma renin in rats receiving enalapril. None of these findings could be explained by changes in the ratio of active and inactive renin. Water diuresis, without natriuresis and with a decrease in potassium urinary excretion, occurred with the higher dose of enalapril. Enalapril did not potentiate the elevation of PRA in two-kidney one-clip Goldblatt hypertensive rats. In conclusion, enalapril produced renin secretion, which was in part β-adrenergically mediated. The negative short feedback loop of angiotensin II and prostaglandins did not appear to be involved. A vasodilator effect, apparently independent of ACE inhibition, was found in intact conscious sodium-replete rats.

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Angiotensin I-converting enzyme-dependent and neutral endopeptidase-dependent generation and degradation of angiotensin II contrarily modulate noradrenaline release: implications for vasopeptidase-inhibitor therapy?

Journal of Hypertension ◽

10.1097/01.hjh.0000173395.42794.cd ◽

2005 ◽

Vol 23 (8) ◽

pp. 1597-1604 ◽

Cited By ~ 2

Author(s):

Walter Raasch ◽

Peter Dominiak ◽

Andreas Dendorfer

Keyword(s):

Angiotensin Ii ◽

Noradrenaline Release ◽

Neutral Endopeptidase ◽

Inhibitor Therapy ◽

Converting Enzyme ◽

Angiotensin I ◽

Angiotensin I Converting Enzyme ◽

Vasopeptidase Inhibitor

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Thirst and brain angiotensin in cattle

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.262.2.r204 ◽

1992 ◽

Vol 262 (2) ◽

pp. R204-R210

Author(s):

J. R. Blair-West ◽

D. A. Denton ◽

M. J. McKinley ◽

R. S. Weisinger

Keyword(s):

Angiotensin Ii ◽

Water Intake ◽

Enzyme Inhibitors ◽

Converting Enzyme ◽

Preoptic Nucleus ◽

Angiotensin I ◽

Converting Enzyme Inhibitors ◽

Median Preoptic Nucleus ◽

Angiotensin I Converting Enzyme ◽

Reduced Water

Cows that were normally hydrated or deprived of water were given intravenous or intracerebroventricular (icv) infusions of angiotensin I converting-enzyme inhibitors (CEI) or angiotensin II antagonists. Normally hydrated Na-deficient cows increased water intake in a dose-related manner in response to icv infusion of angiotensin I (n = 5). The response to 3 micrograms/h angiotensin I was abolished by concurrent icv infusion of the CEI captopril at 3 mg/h but not by intravenous infusion of captopril at 120 mg/h, which reduced Na appetite (n = 5). The icv infusion of captopril at 12 mg/h did not reduce the water intake of cows that were water restricted for 26.5 h (n = 4) or water restricted and Na deficient (n = 4). The icv infusion of the more lipophilic CEI ramipril at 3 mg/h (n = 7) did not reduce the water intake of normally hydrated or dehydrated cows but reduced the "need-free" intake of Na solution by dehydrated cows. The icv infusion of the nonpeptide antagonist Du Pont 753 at 3 mg/h (n = 7) reduced water intake in dehydrated cows. The results indicate that brain angiotensin may be involved in thirst in cattle. The data suggest that this brain angiotensin II may be formed by a pathway that does not include converting enzyme and that is sited inside the blood brain barrier, possibly in the median preoptic nucleus.

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