Functional and biochemical evidence for capsaicin-induced neural endothelin release in isolated working rat heart

In isolated working rat heart, capsaicin elicited a concentration-dependent constriction of coronary arteries accompanied by decline of all cardiac pa rameters recorded (heart rate, coronary and aortic flow, left ventricular d eveloped pressure, and first derivative of left ventricular developed press ure). The following evidence suggests that capsaicin-induced changes are me diated by endothelin of neural origin: (1) the capsaicin (10 nM)-evoked dec rease in coronary flow resulting in deterioration of cardiac functions was mimicked by endothelin (0.1 nM); (2) the selective endothelin ETA receptor antagonist, cycle (D-alpha -aspartyl-L-propyl-D-valyl-L-leucyl-D-tryptophyl ) (1 muM), abolished the cardiac effects provoked by capsaicin (10 nM); (3) reduction of extracellular Ca2+ concentration from 2.4 to 1.2 or 0.6 mM in hibited the cardiac effects of capsaicin (10 nM) but not those induced by e ndothelin (0.1 nM); (4) perfusion of the heart with 0.1% (v/v) Triton X-100 damaged the endothelium and reversed the enhancement of coronary flow evok ed by bethanechol (1 muM), decreased the basal flow, but was without effect on capsaicin-induced coronary constriction; (5) in response to capsaicin c hallenge (10-100 nM), the endothelin concentration measured in coronary eff luent by means of radioimmunoassay increased up to sevenfold but remained u nchanged in the presence of 0.6 mM Ca2+; (6) no reduction of coronary flow was induced by capsaicin (100 nM) applied to the heart of rats which were d esensitised by capsaicin (150 mg/kg). It is concluded that, in the rat hear t, capsaicin acting on VRI capsaicin receptors elicits a release of endothe lin from the sensory nerve terminals. (C) 2001 Elsevier Science B.V. All ri ghts reserved.