COMPARISON OF ACETYLCHOLINE-DEPENDENT RELAXATION IN LARGE AND SMALL ARTERIES OF RAT MESENTERIC VASCULAR BED

The relative contributions of nitric oxide (NO) to in vitro relaxation responses elicited by acetylcholine (ACh) were compared in vessels of different sizes from the rat mesenteric vascular bed. ACh elicited an endothelium-dependent relaxation in phenylephrine-contracted superior mesenteric arteries (SMA, unstretched luminal diam 650 mu m), which was blocked by compounds that inhibited NO, such as hemoglobin (10 mu M), methylene blue (10 mu M), and N-G-monomethyl-L-arginine (1 mM). In contrast, the endothelium-dependent relaxation induced by ACh in phenylephrine-contracted mesenteric resistance arteries (MRA, unstretched luminal diam 200 mu m) was not blocked by hemoglobin, methylene blue, or N-G-monomethyl-L-arginine. KCl (25 mM) partially inhibited the ACh-dependent relaxation in MRA. Furthermore, the ACh-dependent relaxation in MRA was selectively inhibited by the Ca2+-activated K+ channel blocker charybdotoxin (0.1 mu M). In contrast, the ATP-sensitive Kf channel blocker glibenclamide (50 mu M) did not block the ACh-dependent relaxation in MRA. We conclude that 1) NO is a major component of the ACh-dependent relaxation in SMA and 2) the ACh-dependent relaxation of MRA is resistant to NO inhibitors but sensitive to a Ca2+-activated K+ channel blocker. This suggests that an endothelium-derived hyperpolarization factor may be involved in the relaxation of MRA.