STIMULATION OF VASCULAR NA-K+-ATPASE ACTIVITY BY NITRIC-OXIDE - A CGMP-INDEPENDENT EFFECT()

An endothelium-derived factor with the properties of nitric oxide (NO) has been implicated in the regulation of Na+-K+-adenosinetriphosphata se (ATPase) activity in vascular smooth muscle. To examine this phenom enon further and to explore its modulation by guanosine 3',5'-cyclic m onophosphate (cGMP), studies were carried out in the isolated rabbit a orta. Incubation of endothelium-denuded rings with NO (1 mu M) or sodi um nitroprusside (SNP, 10 mu M) caused a time-dependent increase in ou abain-sensitive (OS) Rb-86 uptake with the maximal stimulation (simila r to 170%) seen after 20 min. In contrast, increases in cGMP concentra tion caused by NO and SNP (40- and 20-fold increases, respectively) we re transient, with peak values observed after 2 min and significantly lower values by 10 min. The ability of NO or SNP to increase OS Rb upt ake in endothelium-denuded rings was not mimicked by incubation with 8 -bromo- or dibutyryl-cGMP or increases in cGMP caused by treatment wit h the phosphodiesterase inhibitor isobutylmethylxanthine. Depletion of intracellular cGMP levels by the guanylate cyclase inhibitor LY83583 also did not alter OS Rb uptake. SNP-stimulated OS Rb uptake was not i nhibited by LY83583 in endothelium-denuded rings; however, it was comp letely prevented by the Na+-H+ exchange inhibitors amiloride and ethyl isopropylamiloride. The results suggest that NO stimulates Na+-K+-ATPa se activity in rabbit aorta by a mechanism independent of its ability to increase the intracellular cGMP concentration. They also suggest th at NO may stimulate Na+-K+-ATPase activity secondary to increases in N a+-H+ exchange.