Captopril-induced hypotension is inhibited by the bradykinin
blocker, hoe 140, in na- depleted conscious marmosets.
Panzenbeck, Maret J., Christine L. Loughnan, Jeffrey B. Madwed,
Raymond J. Winquist, and Steven E. Fogal.
Boehringer Ingelheim Pharmaceuticals, Inc., Pharmacology
Department, Research & Development Center, 900 Ridgebury Road,
P.O. Box 368, Ridgefield, CT 06877-0368
APStracts 2:0183H, 1995.
Inhibition of angiotensin converting enzyme (ACE) inhibits formation
of angiotensin II and, by inhibition of kinin metabolism, may also
increase vascular bradykinin (BYK). The present experiments were done
in sodium-depleted, conscious, unrestrained marmosets (n=5-11) to
examine the contribution of BYK to ACE inhibitor-induced hypotension.
Aortic blood pressure and heart rate (HR) were monitored via
telemetry. After sodium depletion (low Na- diet and furosemide),
captopril (1 mg/kg, po) caused a significant (p<.05) decrease in
mean arterial blood pressure (MABP) (-34 +/- 3, maximally, from 79+/
-2 mmHg), but no change in HR compared to vehicle treatment. The BYK
receptor antagonist, HOE 140 (1 mg/kg, sc), significantly inhibited
the hypotensive response to captopril and caused marked tachycardia
(-133+/-14 from 214+/-8 bpm). HOE 140 (1mg/kg sc), followed by
vehicle administration had no effect on MABP but increased HR
similarly. The hypotensive response to captopril was inhibited by HOE
140 regardless of the order of administration or the route of
captopril administration (po vs. sc). The hypotensive response to a
renin inhibitor, A-72517, 3 mg/kg sc was not inhibited by prior HOE
140 administration despite a similar HOE 140-induced tachycardia.
These data suggest that the hypotensive effect of captopril in
sodium-depleted, conscious marmosets is dependent on functional
bradykinin B2 receptors. Also, blockade of B2 receptors uncovers
marked tachycardia in this model, suggesting a tonic effect of
bradykinin on control of HR in marmosets.
Received 3 October 1994; accepted in final form 5 April 1995.
APS Manuscript Number H885-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.