Involvement of nitric oxide pathway in the PAF-induced relaxation of rat thoracic aorta.
1. The mechanism of the vasorelaxant effect of platelet activating factor (PAF) on rat thoracic aorta and the effect of aging on the PAF-induced relaxation were investigated. 2. PAF at concentrations causing relaxation induced marked increases in guanosine 3':5'-cyclic monophosphate (cyclic GMP) production, but did not induce an increase in adenosine 3':5'-cyclic monophosphate (cyclic AMP). 3. Removal of the endothelium by mechanical rubbing, and treatment with the PAF antagonists CV-3988, CV-6209 and FR-900452, the nitric oxide biosynthesis inhibitor, NG-nitro L-arginine, the radical scavenger, haemoglobin, and the soluble guanylate cyclase inhibitor, methylene blue, inhibited PAF-induced relaxation and abolished or attenuated PAF-stimulated cyclic GMP production. 4. The relaxation was greatest in arteries from rats aged 4 weeks. With an increase in age, the response of the arteries to PAF was attenuated. 5. Endothelium-dependent cyclic GMP production also decreased with increase in age of the rats. 6. These results suggest that PAF stimulates production of nitric oxide from L-arginine by acting on the PAF receptors in the endothelium, which in turn stimulates soluble guanylate cyclase in the smooth muscle cells, and so increases production of cyclic GMP, thus relaxing the arteries. Age-associated decrease in PAF-induced relaxation may result from a reduction of cyclic GMP formation.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokushima, Japan.
H
H
Moritoki
T
T
Hisayama
S
S
Takeuchi
H
H
Miyano
W
W
Kondoh
D000375:Aging / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology; D006162:Guanylate Cyclase / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D006454:Hemoglobins; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; D009569:Nitric Oxide; D001120:Arginine; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester