EFFECT OF ANGIOTENSIN CONVERTING ENZYME-INHIBITORS UPON BRAIN ANGIOTENSIN-II BINDING

Objective: The major objective of the current study was to determine whether administration of converting enzyme (CEI) inhibitors produces an alteration in angiotensin II receptor binding in the spontaneously hypertensive rat (SHR). Design: These studies were designed to test the hypothesis that administration of CEI to SHR is associated with a downregulation of the brain angiotensin II receptor. Methods: Ten to fifteen rats per group were used as mating pairs to produce the pups used for cell culture. The specific binding of I-125-angiotensin II to cell membranes was determined in primary neuronal enriched cultures (PNC) developed from whole brains of 1-day-old SHR pups treated in utero with captopril compared with control SHR pups. We then determined the effect of short-term incubation of PNC with captopril or lisinopril upon angiotensin II binding kinetics. Results: I-125-angiotensin II binding in PNC from captopril-treated SHR was decreased compared with cells from control rats. Scatchard analysis revealed no differences in receptor affinity but maximum density of binding sites was less in captopril-treated rats than in controls. Short-term incubation of cells with captopril or lisinopril did not affect angiotensin II binding in neuronal cultures from normotensive rats; however angiotensin II binding was decreased in SHR cells treated with captopril. Angiotensin II binding was also decreased in SHR treated in utero with captopril. Conclusions: These data suggest that CEI decrease I-125-angiotensin II binding in brains from SHR and, furthermore, that the angiotensin II receptor in SHR may be regulated differently from that of normotensive rats.