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 chroni cally hypoxic rats. In isolated blood-perfused lungs, the effects of a rachidonic acid before and after treatment with the cyclooxygenase inh ibitor, meclofenamate, were compared in control (C) rats and rats expo sed 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. M eclofenamate abolished both dilator and constrictor actions of arachid onic 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 hypertensio n of chronic hypoxia and attenuate pulmonary artery pressure. As shown previously, the nitric oxide synthase inhibitor N-nitro-L-arginine me thyl ester (L-NAME) raised pressure in chronically hypoxic but not con trol rats. Meclofenamate and L-NAME given in sequence both raised pulm onary artery pressure in chronically hypoxic rats and the combined ris e was substantial (+13 mmHg). We conclude that, in the conditions of o ur experiment, both nitric oxide and dilator prostanoids are released in hypoxic pulmonary hypertension in rats. Thus, two synthetic process es, both possibly endothelial dependent, may modulate hypoxic pulmonar y hypertension.