Central effects of angiotensins on drinking and blood pressure: structure-activity relationships

The dipsogenic and the pressor effect following intracerebroventricular injection of angiotensins and several C-terminal fragments were studied. Angiotensin I (ANG I), ANG II, ANG III and C-terminal hexa-, penta, tetra- and tripeptide stimulated water intake in water-replete rats and induced significant pressor responses. In both paradigms the most active peptides (in the pmol range) were ANG II, ANG I and ANG III, in that order. Shorter C-terminal peptides appeared to be active, but had to be injected in the nmol range. Latencies to the onset of drinking were less than 45 s for all peptides tested. The C-terminal dipeptide and other dipeptide fragments did not possess detectable dipsogenic activity. The dipsogenic effect of ANG I was inhibited by pretreatment of animals with the converting enzyme inhibitor SQ 14,225. Drinking induced by both ANG I and ANG (4-8) was antagonized by the ANG II-receptor blocking agent Sar1-Ala8-ANG II. It is concluded that conversion of ANG I into ANG II is a prerequisite for the expression of the observed biological activity in the brain. Short C-terminal fragments are capable of stimulating the ANG II receptors, but a peptide chain of 7 amino acids appears necessary for maximal agonistic activity.