Heterogeneous distribution of endothelium-dependent relaxations resistant to N(G)-nitro-L-arginine in rats

Abstract

Endothelium-dependent relaxations that are resistant to inhibitors of nitric oxide synthase probably are mediated by endothelium-dependent hyperpolarization of the vascular smooth muscle. Experiments were performed to examine the distribution of this type of relaxation along the arterial tree of the rat by measuring changes in isometric force. Acetylcholine induced concentration- and endothelium-dependent relaxations in aortas and in pulmonary, common iliac, femoral, mesenteric, and renal arteries contracted with phenylephrine. In the presence of N(G)-nitro-L-arginine, the cumulative administration of acetylcholine induced relaxations only in the femoral, mesenteric, and renal arteries. The calcium ionophore A23187 relaxed mesenteric arteries contracted with phenylephrine in a concentration- and endothelium-dependent manner. The concentration-relaxation curve to A23187 was shifted to the right in the presence of N(G)-nitro-L-arginine. The maximal relaxations induced by lemakalimq, a K+ channel opener, were smaller in those arteries that did not exhibit N(G)-nitro-L-arginine-resistant relaxations. These results suggest that N(G)-nitro-L-arginine-resistant relaxations are more frequently observed in smaller arteries. The arteries that exhibit N(G)-nitro-L-arginine-resistant relaxations may be more sensitive to an endothelium-derived substance that causes hyperpolarization of vascular smooth muscle cells.