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 microns), which was blocked by compounds that inhibited NO, such as hemoglobin (10 microM), methylene blue (10 microM), and NG-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 microns) was not blocked by hemoglobin, methylene blue, or NG-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 Ca(2+)-activated K+ channel blocker charybdotoxin (0.1 microM). In contrast, the ATP-sensitive K+ channel blocker glibenclamide (50 microM) 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 Ca(2+)-activated K+ channel blocker. This suggests that an endothelium-derived hyperpolarization factor may be involved in the relaxation of MRA.
Hwa
J J
JJ
Schering-Plough Research Institute, Kenilworth, New Jersey 07033.
Ghibaudi
L
L
Williams
P
P
Chatterjee
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001158:Arteries; D004730:Endothelium, Vascular / Q000502:physiology; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance; D014664:Vasodilation
D026902:Potassium Channel Blockers; D009599:Nitroprusside; D011189:Potassium Chloride; D000109:Acetylcholine