Myoendothelial coupling in the mesenteric arterial bed; segmental differences and interplay between nitric oxide and endothelin-1

We tested the hypothesis that activated arterial smooth muscle (ASM) stimulates endothelial vasomotor influences via gap junctions and that the significance of this myoendothelial coupling increases with decreasing arterial diameter. From WKY rats, first-, second-, third- and fourth-order branches of the superior mesenteric artery (MA1, MA2, MA3 and MA4 respectively) were isolated and mounted in wire-myographs to record vasomotor responses to 0.16-20 mu mol.L-1 phenylephrine. Removal of endothelium increased the sensitivity (pEC(50)) to phenylephrine in all arteries. The nitric oxide (NO) synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) (100 mu mol.L-1) did not modify pEC(50) to phenylephrine in all denuded arteries, and increased it in intact MA1, MA2 and MA3 to the same extent as denudation. However, in intact MA4, the effect of L-NAME was significantly larger (Delta pEC(50) 0.57 +/- 0.02) than the effect of endothelium removal (Delta pEC(50) 0.20 +/- 0.06). This endothelium-dependent effect of L-NAME in MA4 was inhibited by (i) steroidal and peptidergic uncouplers of gap junctions; (ii) a low concentration of the NO donor sodium nitroprusside; and (iii) by the endothelin-receptor antagonist bosentan. It was also observed during contractions induced by (i) calcium channel activation (BayK 8644, 0.001-1 mu mol.L-1); (ii) depolarization (10-40 mmol.L-1 K+); and (iii) sympathetic nerve stimulation (0.25-32 Hz). These pharmacological observations indicated feedback control by endothelium of ASM reactivity involving gap junctions and a balance between endothelium-derived NO and endothelin-1. This myoendothelial coupling was most prominent in distal resistance arteries.