C-type natriuretic (CNP) caused concentration-dependent relaxations in porcine coronary arteries with a maximal relaxation (10(-6)M) of 46%. Relaxations to CNP in isolated coronary arteries were significantly attenuated with potassium channel antagonists charybdotoxin (10(-7)M) and glibenclamide (10(-7)M). Membrane potential and K+ currents were measured in enzymatically dissociated smooth muscle cells from porcine coronary arteries with patch-clamp techniques in a whole-cell mode (n = 5). CNP caused K+ channel activation and membrane hyperpolarization in a dose-dependent manner. This hyperpolarization was markedly suppressed by the potassium channel inhibitor tetraethylammonium (TEA, 5 mM). These results demonstrate that CNP relaxes porcine coronary arterial smooth muscle by hyperpolarization of vascular smooth muscle through potassium channel stimulation.