Abstract
In experiments lasting 8 h, low (0.5 mg kg-1) or medium (5 mg kg-1) subcutaneous doses of the angiotensin-converting enzyme inhibitor captopril were mildly dipsogenic in sham-operated rats, much more so in rats subjected to bilateral ureteric ligation and not at all in bilaterally nephrectomized rats. Rats with ligated ureters drank enough water to gain weight during the experiments. All other groups lost weight. The enhanced responsiveness of rats with ligated ureters, despite fluid retention, shows that captopril-induced drinking was not secondary to increased renal fluid loss. Ureteric ligation alone which caused some increase in renin secretion was mildly dipsogenic compared with sham operation. Captopril caused further increases in plasma renin concentration and more drinking suggesting that the captopril response is renin-dependent. The failure of the nephrectomized rat to drink after captopril also shows that the response is renin-dependent. The highest dose (50 mg kg-1) of captopril did not at first stimulate drinking, though water intake increased later. Slowness to drink was not the result of general depression of behaviour since drinking in response to subcutaneous hypertonic NaCl or intracranial angiotensin II was not inhibited by the highest dose. Slowness to drink after the highest dose was attributable to blockade of converting enzyme centrally as well as peripherally. This meant that the increased circulating angiotensin I resulting from peripheral blockade of converting enzyme was only slowly converted to angiotensin II in the brain. When cerebral conversion of angiotensin I was prevented by a single intracranial injection of 25 micrograms captopril, drinking in response to the lower doses of captopril was also inhibited in normal rats and in rats with ligated ureters. The same intracranial dose of captopril also inhibited drinking in response to intracranial injections of renin or angiotensin I, but not angiotensin II. The time course of inhibition of renin-induced drinking was similar to that of inhibition of subcutaneous captopril-induced drinking. In conclusion, subcutaneous captopril causes increased water intake through activation of the renal renin-angiotensin system, an effect that is enhanced when the system has already been partly activated by ureteric ligation. Increased circulating angiotensin I resulting from blockade of peripheral converting enzyme must be converted to angiotensin II in the brain in order to stimulate drinking. Drinking is not the consequence of increased fluid loss.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barney C. C., Katovich M. J., Fregly M. J. The effect of acute administration of an angiotensin converting enzyme inhibitor, captopril (SQ 14,225), on experimentally induced thirsts in rats. J Pharmacol Exp Ther. 1980 Jan;212(1):53–57. [PubMed] [Google Scholar]
- Evered M. D., Robinson M. M., Richardson M. A. Captopril given intracerebroventricularly, subcutaneously or by gavage inhibits angiotensin-converting enzyme activity in the rat brain. Eur J Pharmacol. 1980 Dec 19;68(4):443–449. doi: 10.1016/0014-2999(80)90419-7. [DOI] [PubMed] [Google Scholar]
- Fitzsimons J. T., Epstein A. N., Johnson A. K. Petide antagonists of the renin-angiotensin system in the characterisation of receptors for angiotensin-induced drinking. Brain Res. 1978 Sep 22;153(2):319–331. doi: 10.1016/0006-8993(78)90410-9. [DOI] [PubMed] [Google Scholar]
- Fitzsimons J. T. The effect on drinking of peptide precursors and of shorter chain peptide fragments of angiotensin II injected into the rat's diencephalon. J Physiol. 1971 Apr;214(2):295–303. doi: 10.1113/jphysiol.1971.sp009433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fitzsimons J. T. The role of a renal thirst factor in drinking induced by extracellular stimuli. J Physiol. 1969 Apr;201(2):349–368. doi: 10.1113/jphysiol.1969.sp008760. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katovich M. J., Barney C. C., Fregly M. J., McCaa R. E. Effect of an angiotensin converting enzyme inhibitor (SQ 14,225) on beta-adrenergic and angiotensin-induced thirsts. Eur J Pharmacol. 1979 Jun;56(1-2):123–130. doi: 10.1016/0014-2999(79)90441-2. [DOI] [PubMed] [Google Scholar]
- Keeton T. K., Campbell W. B. The pharmacologic alteration of renin release. Pharmacol Rev. 1980 Jun;32(2):81–227. [PubMed] [Google Scholar]
- Lehr D., Goldman H. W., Casner P. Renin-angiotensin role in thirst: paradoxical enhancement of drinking by angiotensin converting enzyme inhibitor. Science. 1973 Dec 7;182(4116):1031–1034. doi: 10.1126/science.182.4116.1031. [DOI] [PubMed] [Google Scholar]
- Ondetti M. A., Rubin B., Cushman D. W. Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents. Science. 1977 Apr 22;196(4288):441–444. doi: 10.1126/science.191908. [DOI] [PubMed] [Google Scholar]
- Schiffrin E. L., Genest J. Mechanism of captopril-induced drinking. Am J Physiol. 1982 Jan;242(1):R136–R140. doi: 10.1152/ajpregu.1982.242.1.R136. [DOI] [PubMed] [Google Scholar]