AJP - Regulatory, Integrative and Comparative Physiology, Vol 273, Issue 2 637-R645, Copyright © 1997 by American Physiological Society

ARTICLES

Enhanced responsiveness of cardiac vagal chemosensitive endings to bradykinin in heart failure

H. D. Schultz, W. Wang, E. E. Ustinova and I. H. Zucker
Department of Physiology and Biophysics, University of Nebraska College of Medicine, Omaha 68198, USA.

There is good evidence that the cardiopulmonary and arterial baroreflexes are blunted in chronic heart failure (HF). Other evidence, however, suggests that the cardiac chemoreflex is enhanced during HF. In the present study, we sought to determine whether HF alters the sensitivity of cardiac vagal chemosensitive endings to bradykinin (BK), an endogenous mediator that activates ventricular C fiber afferents. We measured the activity of cardiac vagal single fibers and compared the afferent responses to left atrial injections of BK and capsaicin in sham-operated and pacing-induced HF dogs. The capsaicin-sensitive endings did not respond to changes in cardiac pressures evoked by vascular snares and were C fiber endings (0.8-2.1 m/s). Most were located in the left heart. There was no difference in rate or pattern of resting discharge of the cardiac vagal fibers between HF and sham groups (1.5 +/- 0.5 vs. 1.3 +/- 0.3 impulses/s, respectively). The afferent response to BK (0.001-1 microgram/kg), but not capsaicin (1-10 micrograms/kg), was greater in HF compared with sham dogs. Captopril (2 mg/kg i.v.) significantly enhanced resting discharge (P < 0.05) from cardiac chemosensitive vagal afferents in HF but not sham dogs. The afferent response to BK in both groups was significantly (P < 0.05) and similarly enhanced. Indomethacin (5 mg/kg i.v.) significantly inhibited resting discharge (P < 0.05) and nearly abolished the afferent responses to lower doses of BK in HF, but did not affect resting discharge and less effectively attenuated responses to BK in sham dogs. Responses to capsaicin did not differ between HF and sham animals. From these results, we conclude that 1) resting discharge from cardiac vagal chemosensitive endings is not altered in HF, 2) these vagal endings exhibit an enhanced sensitivity to exogenous BK but not to capsaicin in the HF state, 3) angiotensin-converting enzyme activity inhibits resting discharge from these afferents in HF, and 4) the cyclooxygenase system contributes to the enhanced BK responsiveness of cardiac chemosensitive endings in HF.

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