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.