Abstract

Experiments were designed to determine the mechanism of action underlying relaxation of vascular smooth muscle induced by ammonium ions. In particular, the possibility that these ions might be an endothelium-derived relaxing factor was examined. Rings of large canine femoral, mesenteric and coronary arteries and of small arteries from the gracilis muscle were suspended in organ chambers for the recording of isometric force. Membrane potential was recorded with intracellular microelectrodes in smooth muscle cells from the mesenteric artery. Ammonium ions induced relaxation which were independent of the presence of the endothelium. The relaxations were not prevented by adrenergic, serotonergic, muscarinic and histaminic blockers, by scavengers of oxygen-derived radicals or by inhibitors of soluble guanylate cyclase. The relaxations were prevented by a decrease in extracellular calcium concentration and by inhibition of the Na+/K+ pump. The results are compatible with the hypothesis that the relaxation induced by ammonium ions is related to changes in intracellular pH and, at high concentration of these ions, possibly to activation of the Na+/K+ pump. Ammonium ions are neither the endothelium-derived relaxing factor which activates guanylate cyclase nor the factor that induces endothelium-derived hyperpolarization. Inasmuch as relatively low concentrations of the ion induce relaxation of small arteries of skeletal muscle, they could contribute to exercise hyperemia.