Interaction between Na+,K+ exchanges and the direct inhibitory effect of acetylcholine on canine femoral arteries

Abstract

We studied the mechanism by which acetylcholine causes relaxation of vascular smooth muscle cells. Isolated rings of femoral arteries of the dog were mounted for isometric tension recording in organ chambers filled with Krebs-Ringer's solution. This preparation was used because it is not densely innervated, and it is sensitive to the direct inhibitory effect of acetylcholine. Acetylcholine caused dose-dependent relaxation during contractions evoked by norepinephrine and potassium (24 mEq/liter); at higher potassium concentrations, the inhibitory effect of acetylcholine was progressively depressed. The inhibitory effect of acetylcholine was not altered by phentolamine, propranolol, or hexamethonium; it was inhibited by atropine, indicating its muscarinic nature. Anoxia, moderate cooling, ouabain, reduction of the potassium concentration, or reduction of the sodium concentration abolished the acetylcholine-induced relaxation. Preparations incubated in low potassium solution and made to contract with norepinephrine responded to an increase in potassium concentration with transient relaxations. These were depressed by anoxia and abolished by moderate cooling, ouabain, and reduction of the sodium concentration. Verapamil reduced the potassium-induced relaxation, but not that caused by acetylcholine. These results suggest that Na+,K+-ATPase -ATPase is involved indirectly in the inhibitory effect of acetylcholine on vascular smooth muscle cells.