Endothelium-dependent relaxation resistant to NG-nitro-L-arginine in rat aorta.
Experiments were designed to determine whether cyclic GMP-independent relaxation is involved in the endothelium-dependent vascular relaxation response of rat aortic strip to acetylcholine. The relaxation response to acetylcholine in the presence of 3 x 10(-4) M NG-nitro-L-arginine was apparent when the precontraction was induced by norepinephrine at 5 x 10(-9) M or 10(-8) M. The relaxation response to acetylcholine resistant to NG-nitro-L-arginine was abolished by 10(-6) M atropine, 10 mM tetraethylammonium, or endothelium removal, but was not inhibited by 10(-5) M indomethacin, 3 x 10(-6) M oxyhemoglobin or 10(-5) M glibenclamide. The response was virtually abolished when the vascular strips had been preconstricted with 20 mM KCl. The increase in vascular cyclic GMP levels induced by 10(-5) M acetylcholine was completely abolished by 3 x 10(-4) M NG-nitro-L-arginine. These results suggest that acetylcholine-induced endothelium-dependent relaxation resistant to NG-nitro-L-arginine in rat aorta is unmasked when the precontractile force is caused by lower concentrations of norepinephrine and the relaxation is mediated by a cyclic GMP-independent mechanism, possibly an endothelium-derived hyperpolarizing factor.
Hatake
K
K
Department of Legal Medicine, Hyogo College of Medicine, Japan.
Wakabayashi
I
I
Hishida
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001685:Biological Factors / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019335:Nitroarginine; D009638:Norepinephrine / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001685:Biological Factors; D010108:Oxyhemoglobins; D026902:Potassium Channel Blockers; D013757:Tetraethylammonium Compounds; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D019789:Tetraethylammonium; D001285:Atropine; D001120:Arginine; D010208:Papaverine; D006152:Cyclic GMP; D000109:Acetylcholine; D005905:Glyburide; D009638:Norepinephrine; D007213:Indomethacin