Nitric oxide synthase responsible for L-arginine-induced relaxation of rat aortic rings in vitro may be an inducible type.
1. Characteristics of L-arginine-induced non-endothelial nitric oxide (NO) formation in rat isolated thoracic aorta were investigated. 2. Relaxation to L-arginine in arterial rings devoid of endothelium developed about 2 h after the first challenge with L-arginine and reached a maximum after a further 4 h of incubation. 3. After the arteries had relaxed in response to L-arginine, guanosine 3':5'-cyclic monophosphate (cyclic GMP) production was stimulated. In fresh arteries that had not yet relaxed in response to L-arginine, L-arginine failed to elevate cyclic GMP levels. 4. Glucocorticoids, actinomycin D and polymyxin B prevented the development of L-arginine-induced relaxation and L-arginine-stimulated increase in cyclic GMP formation. 5. Once L-arginine-induced relaxation developed, these agents no longer suppressed the relaxation and increase in cyclic GMP formation to L-arginine. 6. From these results, it is suggested that in the isolated thoracic aorta of the rat, endotoxin in the medium triggers induction of a non-endothelial NO synthase during prolonged incubation, which accelerates production of NO from added L-arginine to cause relaxation of the arteries via cyclic GMP. Glucocorticoids and protein synthesis inhibitors may prevent induction of NO synthase. It is suggested that the NO synthase mediating the production of muscle-derived NO from L-arginine is an inducible type.
Moritoki
H
H
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
Takeuchi
S
S
Hisayama
T
T
Kondoh
W
W
D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D001120:Arginine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004790:Enzyme Induction; D005938:Glucocorticoids / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase; D010656:Phenylephrine / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar
D005938:Glucocorticoids; D003609:Dactinomycin; D010656:Phenylephrine; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP