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Captopril-induced hypotension is inhibited by the bradykinin blocker HOE-140 in Na(+)-depleted marmosets.

Abstract
Inhibition of angiotensin-converting enzyme (ACE) inhibits formation of angiotensin II and, by inhibition of kinin metabolism, may also increase 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. Aortic blood pressure and heart rate (HR) were monitored via telemetry. After 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 no change in HR compared with vehicle treatment. The bradykinin receptor antagonist HOE-140 (1 mg/kg sc) significantly inhibited the hypotensive response to captopril and caused marked tachycardia (+133 +/- 14 beats/min from 214 +/- 8 beats/min). HOE-140 (1 mg/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 (by mouth vs. subcutaneously). 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.
AuthorsM J Panzenbeck, C L Loughnan, J B Madwed, R J Winquist, S E Fogal
JournalThe American journal of physiology (Am J Physiol) Vol. 269 Issue 4 Pt 2 Pg. H1221-8 (Oct 1995) ISSN: 0002-9513 [Print] United States
PMID7485552 (Publication Type: Journal Article)
Chemical References
  • Piperazines
  • Thiazoles
  • icatibant
  • Captopril
  • Sodium
  • Renin
  • zankiren hydrochloride
  • Bradykinin
Topics
  • Administration, Oral
  • Animals
  • Blood Pressure (drug effects)
  • Bradykinin (analogs & derivatives, antagonists & inhibitors, pharmacology)
  • Callithrix
  • Captopril (antagonists & inhibitors, pharmacology)
  • Female
  • Hypotension (chemically induced, physiopathology)
  • Injections, Subcutaneous
  • Male
  • Piperazines (pharmacology)
  • Renin (antagonists & inhibitors)
  • Sodium (deficiency, metabolism)
  • Thiazoles (pharmacology)

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