CAPTOPRIL-INDUCED HYPOTENSION IS INHIBITED BY THE BRADYKININ BLOCKER HOE-140 IN NA-DEPLETED MARMOSETS()

Inhibition of angiotensin-converting enzyme (ACE) inhibits formation o f angiotensin II and, by inhibition of kinin metabolism, may also incr ease vascular bradykinin. The present experiments were done in sodium- depleted, conscious, unrestrained marmosets (n = 5-11) to examine the contribution of bradykinin to ACE inhibitor-induced hypotension. Aorti c blood pressure and heart rate (HR) were monitored via telemetry. Aft er sodium depletion (low-sodium diet and furosemide), captopril (1 mg/ kg po) caused a significant (P < 0.05) decrease in mean arterial blood pressure (MABP) (-34 +/- 3 mmHg, maximally, from 79 +/- 2 mmHg) but n o change in HR compared with vehicle treatment. The bradykinin recepto r antagonist HOE-140 (1 mg/kg sc) significantly inhibited the hypotens ive response to captopril and caused marked tachycardia (+133 +/- 14 b eats/min from 214 +/- 8 beats/min). HOE-140 (1 mg/kg sc) followed by v ehicle administration had no effect on MABP but increased HR similarly . The hypotensive response to captopril was inhibited by HOE-140 regar dless of the order of administration oi the route of captopril adminis tration (by mouth vs. subcutaneously). The hypotensive response to a r enin inhibitor, A-72517 (3 mg/kg sc), was not inhibited by prior HOE-1 40 administration despite a similar HOE-140-induced tachycardia. These data suggest that the hypotensive effect of captopril in sodium-deple ted, conscious marmosets is dependent on functional bradykinin Bz rece ptors. Also, blockade of Bz receptors uncovers marked tachycardia in t his model, suggesting a tonic effect of bradykinin on control of HR in marmosets.