ENDOTHELIUM DERIVED NITRIC OXIDE-DEPENDENT RESPONSE TO HYPOXIA IN PIGLET INTRAPULMONARY ARTERIES. † 2110

Abstract

Hypoxic pulmonary vasoconstriction is the physiologic mechanism for maintaining the optimal balance of ventilation and perfusion. In the present work we have studied the involvement of eicosanoids and nitric oxide (NO) in the response to hypoxia in isolated intrapulmonary (third branch) arteries from 10-17 days old piglets. The response to hypoxia was assessed in arterial rings preconstricted with 30 mM KCl, by switching the gas aerating the organ chambers from one composed of 21% O2-5% CO2- balance N2(pO2 145 ± 1.27 mmHg) to a mixture of 5% CO2-balance N2 (pO2 33.87 ± 0.24 mmHg). Under these conditions hypoxia produced a transient vasoconstriction (121 ± 3% of the precontraction value) reaching the peak in 3-5 minutes, followed by a relaxation which was maximal in 10-15 min. The first contractile phase was not present in endothelium-denuded arteries or after the incubation with the NO synthase inhibitor L-NAME (10-4M), or the guanylate cyclase inhibitor methylene blue (10-5M). No changes in the hypoxia-induced vasoconstriction were observed after preincubation with the NO precursor L-arginine (10-5M), the cyclooxigenase inhibitor meclofenamate(10-5M), the lipooxygenase inhibitor AA 861 (10-5M), or the cytochrome P450 oxidase inhibitor SKF 525A (10-5M). The relaxant phase was endothelium-independent. These findings demonstrate that the contractile response to hypoxia in isolated intrapulmonary porcine artery is caused by the loss of the inhibitory effects of endothelium derived NO on the vascular tone. Eicosanoids does not appear to be involved in this response.