Differential effect of nitric oxide synthase inhibitors on acetylcholine-induced relaxation of rat pulmonary and celiac artery rings.
The effect of NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) on acetylcholine (ACh) induced relaxation of rat intrapulmonary artery and celiac artery ring segments was studied in vitro with and without meclofenamate pretreatment. L-NMMA, and to a lesser extent L-NAME, raised baseline tone more in pulmonary than celiac arteries. Pretreatment of pulmonary and celiac artery rings with meclofenamate did not alter this contractile effect. Pulmonary artery and celiac artery ring segments were precontracted with phenylephrine, and cumulative concentration-relaxation curves to ACh were obtained before and after incubation of the rings with L-NAME or L-NMMA. L-NAME inhibited the ACh-induced relaxation of pulmonary arterial rings at 10000 fold lower concentrations than those needed to only partly inhibit the ACh-induced relaxation of celiac artery rings. L-NMMA (10-300 microM) inhibited the ACh-induced relaxation of pulmonary arterial rings in a concentration-dependent manner, whereas L-NMMA (300 microM) only partially inhibited the ACh-induced relaxation of celiac artery rings. The inhibition of ACh-induced relaxation by L-NAME and to a lesser extent by L-NMMA was more when pulmonary and celiac artery rings were pretreated with meclofenamate (1.0 microM). These results suggest that in the pulmonary artery nitric oxide plays a greater role in the modulation of baseline vascular tone and ACh-induced relaxation than in the celiac artery. In addition, cyclooxygenase products do not contribute to the direct contractile responses to L-NAME and L-NMMA in both the pulmonary and celiac artery rings but do modulate the ACh-induced relaxation of these vessels.
Yaghi
A
A
A.C. Burton Vascular Biology Laboratory, Victoria Hospital, London Health Sciences Centre, Canada.
Paterson
N A
NA
McCormack
D G
DG
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002445:Celiac Artery / Q000187:drug effects* / Q000201:enzymology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester