Date of Award

1984

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Abstract

Beta-adrenergic drugs, such as isoproterenol, potently stimulate renin secretion and drinking. It is controversial, however, whether the renin-angiotensin system directly mediates the dipsogenic response.;Isoproterenol (0.1 mg/kg, S.C.) alone caused rats to drink. Low doses of captopril (0.1-1.0 mg/kg, S.C.) which inhibit angiotensin II synthesis in the circulation but not in the brain dose-dependently enhanced isoproterenol-induced drinking whereas higher doses of captopril (5.0-100 mg/kg, S.C.) which inhibit angiotensin II synthesis in the brain as well, caused a dose-dependent inhibition of the response. The highest doses of captopril, either 100 mg/kg, S.C. or 20 mg/h, I.V., completely blocked the drinking response to isoproterenol suggesting that the renin-angiotensin system has a direct and essential role in isoproterenol-induced drinking.;The abolition of the drinking response to isoproterenol by captopril could not be attributed to either a general debility or exacerbated hypotension since rats treated similarly still drank to 12 h water deprivation. Also, the low and high doses of captopril lowered arterial pressure similarly yet the low dose enhanced the drinking response to isoproterenol and the high dose abolished it.;Enhancement of isoproterenol-induced drinking by the low dose of captopril appears to depend on the renal renin-angiotensin system since this dose enhanced drinking to all thirst stimuli tested which increase renin secretion from the kidney but had no effect on drinking to I.P. injections of hypertonic saline which inhibits renin secretion.;When S.C. injections of a low dose of captopril were combined with I.C.V. injections of captopril (20 ug/rat), the drinking response to isoproterenol was abolished suggesting that enhancement is the result of increased synthesis of angiotensin II in the brain and that high S.C. doses of captopril are inhibiting because they block both cerebral and peripheral converting enzyme.;The results of this study firmly support the hypothesis that the renin-angiotensin system has a direct and essential role in the drinking response to isoproterenol and suggest as well that it is involved in the normal control of water intake.

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