Mechanism of action of nitric oxide donors on voltage-activated calcium channels in vascular smooth muscle cells

The effects of nitric oxide (NO) donors on inward barium current (I-Ba) in freshly isolated smooth muscle cells (SMC) of the guinea pig mesenteric artery and on inward calcium current (I-Ca) in SMC of the canine coronary artery were studied using a patch-clamp recording technique in whole-cell configuration. The inward current in SMC of the guinea pig artery was shown to flow through a single type of calcium channels, which have characteristics of high-threshold slowly inactivated channels of L-type. Nitroglycerin (NG) and sodium nitroprusside (NP) reversibly inhibited I-Ba in a dose-dependent manner. Effects of NO donors on I-Ba were related to the changes in voltage-dependent properties of calcium channels. In particular, NG and NP accelerated the current inactivation, and their blocking effects increased with the membrane depolarization. Methylene blue, the guanylate cyclase inhibitor, decreased the inhibitory action of NG on I-Ba by a factor of 5. 8-Bromo-cGMP, the membrane-permeant cGMP analog, evoked I-Ba inhibition similar to that caused by NO donors. In the canine coronary artery, NO donors also inhibited I-Ca flowing through the L-type calcium channels. It has been concluded that NO originating from NG and NP inhibits activity of L-type calcium channels in vascular SMC; it is possible that cGMP-dependent processes are involved.