Mechanism of the dipsogenic action of tetradecapeptide renin substrate in dogs.

Dogs with chronically implanted third ventricular cannulae showed significant drinking responses to central injections of angiotensin II and tetradecapeptide renin substrate (TDP). The threshold dose for angiotensin II was 1 pmol and for TDP was 70 pmol. Although central injections of TDP led to drinking and appearance of angiotensin II in cerebrospinal fluid, renin substrate prepared from dog cerebrospinal fluid had no effect. The dipsogenic action of TDP was blocked by prior administration of converting enzyme inhibitor SQ20881 (P less than 0.01) but was not affected by either pepstatin or N-acetyl-pepstatin. Thus, converting enzyme acts directly on TDP to produce angiotensin I and then angiotensin II. The results of the present study do not provide evidence for the presence of an enzyme in the brain with renin-like activity.