OXYGEN OR LOW CONCENTRATIONS OF NITRIC-OXIDE REVERSE PULMONARY VASOCONSTRICTION INDUCED BY NITRIC-OXIDE SYNTHESIS INHIBITION IN RABBITS

The objective of this study was to investigate the role of nitric oxid e and oxygen in the regulation of pulmonary vascular resistance, espec ially by means of substitution with nitric oxide after inhibition of e ndogenous nitric oxide formation. In artificially ventilated open-ches t rabbits pulmonary vascular resistance at normoxic ventilation (FIO2 = 21%) was 56 +/- 6 cmH(2)O ml(-1) min(-1) 1000(-1) (mRU(L)). N-omega- nitro-L-arginine methyl ester (L-NAME, 30 mg kg(-1)), an inhibitor of NO synthase, increased pulmonary vascular resistance to 122 +/- 17 mRU (L) at normoxic ventilation. In response to L-NAME there was also an i ncrease in mean arterial blood pressure. Exogenous nitric oxide (0.014 -9 p.p.m. in the inhaled air) dose-dependently and reversibly countera cted the effect of L-NAME on pulmonary vascular resistance at normoxic ventilation, without affecting systemic brood pressure. In addition, the L-NAME-induced vasoconstriction was critically dependent on oxygen . Thus, during hypoxic ventilation (FIO2 = 10%) the pulmonary vascular resistance was increased approximately four-fold by the presence of L -NAME (30mg kg(-1)), and increments in FIO2 (21-100%) dose-dependently and reversibly counteracted the effect of L-NAME on pulmonary vascula r resistance. Taken together these findings demonstrate that inhalatio n of low doses of NO may act as a replacement when endogenous NO synth esis is inhibited, and that pulmonary vasoconstriction induced by NO s ynthesis inhibition is likely to be the result of interference with ox ygen-dependent regulatory mechanisms. Endogenous NO cooperates with ox ygen to evoke a vasodilator component of the pulmonary hypoxic presser response, balancing a hitherto unknown constrictor mechanism.