Increased or decreased thirst caused by inhibition of angiotensin-converting enzyme in the rat.

AUTOR(ES)

Evered, M D

RESUMO

We have investigated the effects on water intake of subcutaneous (S.C.) injections of low (0.5 mg/kg) and high (100 mg/kg) doses of captopril, an inhibitor of angiotensin-converting enzyme (CE). Low doses block the synthesis of angiotensin II only in the circulation whereas high doses block CE in both the blood and the brain. The low dose of captopril enhanced drinking in response to three hypotensive drugs, isoprenaline (0.1 mg/kg, S.C.), phentolamine (5 mg/kg, S.C.) and serotonin (2 mg/kg, S.C.), whereas the high dose of captopril abolished drinking in response to these stimuli. The low dose of captopril also enhanced drinking in response to histamine (0.25-5.0 mg/kg, intraperitoneal, I.P.), but in this case the high dose of captopril only partially reduced the drinking response. The low dose of captopril enhanced drinking after 24 h water deprivation but high doses had no significant effect on deprivation-induced thirst. Hypovolaemia was produced either by injecting polyethylene glycol (30% w/v, 10 ml/kg) S.C. or by replenishing the cellular deficit in water-deprived rats with 10 ml water (by gavage). The low dose of captopril enhanced the drinking response to hypovolaemia but the high dose had no significant effect. Neither the high nor the low dose of captopril significantly affected drinking in response to cellular dehydration caused by injecting 2 M-NaCl (2 ml) I.P. or by replenishing the extracellular deficit in water-deprived rats (10 ml balanced salt solution by gavage). Nephrectomy (but not ligation of the ureters) or injections of propranolol (5 mg/kg, S.C.) to prevent renin secretion prevented the enhancement of deprivation-or serotonin-induced thirst by the low dose of captopril. The low dose of captopril did not enhance drinking in response to I.V. injections of renin (1 Goldblatt unit), or intracerebroventricular (I.C.V.) injections of angiotensin I or II. The high dose of captopril blocked drinking in response to I.V. injections of renin or I.C.V. injections of angiotensin I but did not reduce drinking in response to angiotensin II, I.C.V. These results are consistent with the hypothesis that blocking CE only in the circulation enhances drinking in response to hypotension or hypovolaemia because angiotensin I, accumulating in high concentration in the blood, enters the brain and is converted intracerebrally to angiotensin II. These findings suggest that the enhancement of drinking caused by low doses of captopril s.c. is a sensitive indicator of whether the renin- angiotensin system participates at all in the regulatory response to a particular stimulus to drink.(ABSTRACT TRUNCATED AT 400 WORDS)

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