Renin dependence of captopril-induced drinking after ureteric ligation in the rat.

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RESUMO

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.

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