Role of Na+-K+ATPase in cyclic GMP-mediated relaxation of canine pulmonary artery smooth muscle cells

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Abstract
1. Sodium-potassium adenosine triphosphate (Na(+)-K+ ATPase) plays a role in the regulation of vascular tone, but contribution of this enzyme to intravasodilator-induced pulmonary vasodilation remains uncertain. We thus studied the interaction between guanosine 3':5'-cyclic monophosphate (cyclic GMP) and Na(+)-K+ ATPase in smooth muscle cells isolated from canine pulmonary artery. 2. To assess the contractile properties, changes in smooth muscle cell length were determined microscopically. Application of potassium chloride (KCl) shortened the cell length, an effect which was reduced by sodium nitroprusside and 8-bromo-cyclic GMP in a concentration-dependent manner. Pretreatment of cells with the cyclic GMP-dependent kinase inhibitor KT 5823 (2 microM) abolished the effects of sodium nitroprusside and 8-bromo-cyclic GMP. 3. Ouabain (0.3 microM) did not alter the KCl-induced muscle shortening, but inhibited the relevant responses to sodium nitroprusside and 8-bromo-cyclic GMP. 4. Incubation of smooth muscle cells with sodium nitroprusside concentration-dependently increased intracellular cyclic GMP levels and ouabain-sensitive 86Rb uptake, and these values were significantly correlated. In the presence of KT 5823, sodium nitroprusside increased cyclic GMP levels but did not alter ouabain-sensitive 86Rb uptake. 5. These results suggest that there is a link between accumulation of intracellular cyclic AMP and activation of sarcolemmal Na(+)-K+ ATPase in pulmonary artery smooth muscle cells and that this link may be involved in the sodium nitroprusside-induced pulmonary vasodilatation.
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