ROLE OF THE SARCOLEMMAL SODIUM-PUMP IN NITROPRUSSIDE-INDUCED VASODILATION OF THE PULMONARY ARTERY

To elucidate the mechanism of nitrovasodilator-induced pulmonary vasod ilation, we examined the role of sodium pump and K+ channels in the re laxant responses of canine pulmonary arterial rings to sodium nitropru sside (SNP) under isometric conditions in vitro. Pretreatment with the sodium pump inhibitor ouabain attenuated the SNP-induced vasodilation of KCl-contracted tissues, so that the maximal relaxation decreased f rom 90 +/- 7 to 62 +/- 6% (P < 0.01), and the negative logarithm of SN P concentration required to produce a half-maximal effect (pD(2)) decr eased from 5.9 +/- 0.4 to 5.1 +/- 0.4 (P < 0.01). This effect was not altered by mechanical removal of the endothelium. In contrast, pretrea tment with K+ channel blockers including iberiotoxin, apamin and glibe nciamide did not change the relaxant responses to SNP. Incubation of e ndothelium-denuded rings with SNP increased ouabain-sensitive Rb-86 up take in a dose-dependent manner, an effect that was inhibited by KT 58 23, a cGMP-dependent protein kinase inhibitor. These results suggest t hat activation of sarcolemmal sodium pump may be involved in the nitro vasodilator-induced cGMP-mediated pulmonary vasodilation, whereas K+ c hannels may play a less important role in this action.