Attenuation of chronic hypoxic pulmonary hypertension in rats by cyclooxygenase products and by nitric oxide.
We wanted to assess the respective roles of arachidonic acid products and nitric oxide in the modulation of pulmonary hypertension in chronically hypoxic rats. In isolated blood-perfused lungs, the effects of arachidonic acid before and after treatment with the cyclooxygenase inhibitor, meclofenamate, were compared in control (C) rats and rats exposed for two weeks to 10% oxygen (chronic hypoxia CH). Arachidonic acid caused mixed dilator and constrictor effects during both normoxia and hypoxia; dilatation was more prominent in chronically hypoxic rats. Meclofenamate abolished both dilator and constrictor actions of arachidonic acid; it raised baseline, normoxic pulmonary artery pressure, in chronically hypoxic but not control rats, which suggests that dilator products of arachidonic acid are released in the pulmonary hypertension of chronic hypoxia and attenuate pulmonary artery pressure. As shown previously, the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) raised pressure in chronically hypoxic but not control rats. Meclofenamate and L-NAME given in sequence both raised pulmonary artery pressure in chronically hypoxic rats and the combined rise was substantial (+13 mmHg). We conclude that, in the conditions of our experiment, both nitric oxide and dilator prostanoids are released in hypoxic pulmonary hypertension in rats. Thus, two synthetic processes, both possibly endothelial dependent, may modulate hypoxic pulmonary hypertension.
Russell
P
P
Dept of Medicine, Royal Hallamshire Hospital, Sheffield, UK.
Wright
C
C
Kapeller
K
K
Barer
G
G
Howard
P
P
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004106:Dilatation; D015237:Dinoprost / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D016718:Arachidonic Acid; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D001120:Arginine; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester