ENDOTHELIUM-INDEPENDENT RELAXATION AND HYPERPOLARIZATION TO C-TYPE NATRIURETIC PEPTIDE IN PORCINE CORONARY-ARTERIES

Endothelial cells produce C-type natriuretic peptide (CNP), which has been proposed as an endothelium-derived hyperpolarizing factor. In por cine coronary arteries, we investigated the vasodilatory effects of CN P and compared them with endothelium-dependent relaxations and hyperpo larizations to bradykinin. Isolated epicardial porcine coronary arteri es were studied in organ chambers, and concentration-response curves t o CNP and bradykinin were obtained. Membrane potential was measured in endothelial cells and smooth muscle of intact porcine coronary arteri es during stimulation with CNP or bradykinin. In precontracted porcine coronary arteries with or without endothelium, CNP (10(-10)-10(-6) M) evoked relaxations (maximum, 42 +/- 4%) smaller than those evoked by bradykinin (100 +/- 1%), blunted in preparations contracted by KCl ins tead of U46619 (9,11-dideoxy-11a,9a-epoxymethano-prostaglandin F-2 alp ha; p < 0.05) and unaffected by inhibition of NO synthase (NS). CNP ev oked hyperpolarization of vascular smooth muscle of similar magnitude in endothelium-intact (-4.4 +/- 1 mV) and endothelium-denuded (-4.6 +/ - 1 mV) porcine coronary arteries. Bradykinin (10(-10)-10(-6) M) evoke d concentration-dependent relaxations in preparations with endothelium only. Although atrial natriuretic peptide-receptor antagonist HS-142- 1 (25 mu M) slightly reduced the sensitivity to bradykinin (log shift at IC50, twofold; p < 0.05), it had no effect on the maximal response to bradykinin. Inhibition of NO synthase partially attenuated, whereas high potassium chloride (30 mM) markedly inhibited relaxations to bra dykinin (p < 0.05). Hyperpolarization to bradykinin was much more pron ounced than that to CNP (-17 -/+ 3 mV; p < 0.05 vs. CNP) and was obser ved in endothelium-intact preparations only and unaffected by HS-142-1 . In conclusion, in contrast to bradykinin, CNP induces endothelium-in dependent and weaker relaxation and hyperpolarization of coronary arte ry vascular smooth muscle, suggesting that CNP is an unlikely mediator of endothelium-dependent hyperpolarization of porcine coronary arteri es.