Modulation of endothelium-derived nitric oxide in canine femoral veins.
Experiments were designed to determine whether nitric oxide was the mediator of increased endothelium-dependent relaxations in veins proximal to an arteriovenous fistula. A fistula was prepared between femoral arteries and veins in dogs. After 6 wk, veins proximal to the fistula were removed, cut into rings, and suspended for the measurement of isometric force in organ chambers. In some rings the endothelium was removed deliberately. NG-monomethyl-L-arginine (L-NMMA) caused contraction in three of six fistula-operated veins with and without endothelium. In rings contracted submaximally with prostaglandin F2 alpha, acetylcholine and the alpha 2-adrenergic agonist UK-14,304 cause e tylcholine and the alpha 2-adrenergic agonist UK-14,304 caused endothelium-dependent, concentration-dependent relaxations that were greater in fistula compared with sham-operated veins. These relaxations were reduced by L-NMMA. Calcium ionophore A23187 caused comparable endothelium-dependent relaxations in fistula- and sham-operated veins that were unaffected by L-NMMA. There were no differences in either calcium-dependent or -independent activity of nitric oxide synthase isolated from fistula- and sham-operated veins. Positive staining for nitric oxide synthase was present in both the endothelium and media of fistula-operated veins. These results indicate that nitric oxide mediates increased endothelium-dependent relaxations to acetylcholine and alpha 2-adrenergic agonists in fistula-operated veins. Therefore, chronic increases in blood flow and oxygen tension modify selectively receptor-coupled production of nitric oxide in endothelium and smooth muscle of veins.
Miller
V M
VM
Department of Surgery, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Barber
D A
DA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D005268:Femoral Vein / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000068438:Brimonidine Tartrate; D019001:Nitric Oxide Synthase