Endothelium-derived relaxing factor and nitric oxide possess identical pharmacologic properties as relaxants of bovine arterial and venous smooth muscle.
The principal objective of this study was to compare and contrast the vascular smooth muscle-relaxing properties of endothelium-derived relaxing factor (EDRF) and nitric oxide (NO) in two different assay systems. In one system, precontracted rings of bovine intrapulmonary artery and vein and coronary artery were used to compare the relaxant effects of endothelium-dependent vasodilators, NO, S-nitroso-N-acetylpenicillamine, glyceryl trinitrate, prostacyclin and isoproterenol. In a second system, a bioassay superfusion cascade procedure was employed to compare the relaxant effects and biologic stability of EDRF and NO. Acetylcholine and bradykinin elicited concentration-dependent but transient relaxant responses in arterial and venous rings, respectively. NO and S-nitroso-N-acetylpenicillamine, which generates NO in solution, elicited similar transient relaxant responses in endothelium-denuded arterial and venous rings. Glyceryl trinitrate, however, produced sustained relaxations, as did isoproterenol and prostacyclin. Utilizing a bioassay superfusion cascade system in which intact perfused artery or vein was the source of EDRF and three endothelium-denuded arterial or venous strips mounted in series served as the detector of EDRF or NO, the relaxation profile and biologic stability of superfused EDRF were compared with those of superfused NO. Arterial or venous perfusion with acetylcholine or bradykinin, respectively, and superfusion of NO over the strips produced characteristic decremental relaxant responses in the three vascular strips and revealed the highly unstable nature of EDRF and NO (T1/2 = 3-5 sec for both). The relaxation profile of EDRF was indistinguishable from that of NO.(ABSTRACT TRUNCATED AT 250 WORDS)
Ignarro
L J
LJ
Department of Pharmacology, UCLA School of Medicine.
Buga
G M
GM
Byrns
R E
RE
Wood
K S
KS
Chaudhuri
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay; D001688:Biological Products / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D001688:Biological Products; D010108:Oxyhemoglobins; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D005996:Nitroglycerin; D006152:Cyclic GMP; D000109:Acetylcholine; D011188:Potassium; D001920:Bradykinin