Inhibition of renin-like activity in marmoset tissues by the renin inhibitor CGP 29 287.
This study investigated the contribution of tissue renin-like activity to the acute hypotensive response induced by the potent and specific inhibitor of primate renin, CGP 29 287. Furosemide-pretreated marmosets (5mg/kg, i.m.) were killed 30 min after bolus injection of CGP 29 287 (1 mg/kg, i.v., n = 4). At this time, plasma renin activity is completely inhibited and the hypotensive response is maximal. Control marmosets received vehicle (0.9% saline, 1 ml/kg, i.v.). Renin-like activity was measured by the rate of angiotensin I (ANG I) formation after incubation of tissue homogenates with sheep angiotensinogen at pH 6.0 and 7.4. Activity was detected in the brain, heart, aorta and kidney of CGP 29 287-treated and control marmosets, and there were no significant differences in the values between the two groups. Addition of CGP 29 287 (5 X 10(-6) mol/l) to tissue homogenates in vitro inhibited ANG I formation (greater than 80%). These results indicate that CGP 29 287 is an inhibitor of tissue renin-like activity in vitro, but does not inhibit activity in these tissues after acute administration in vivo. Thus, the acute hypotensive response to CGP 29 287 appears to be due to inhibition of circulating renin only.
Wood, JM; Baum, HP; Carleton, J; Dzau, VJ
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