HYPOXIC VASOCONSTRICTION IN RAT PULMONARY AND MESENTERIC-ARTERIES

Hypoxic vasoconstriction was investigated in isolated pulmonary and me senteric arteries of the rat. Experiments were performed on large (sim ilar to 2 mm pulmonary, similar to 0.8 mm mesenteric) and small (100-3 50 mu m) arteries. Hypoxia [oxygen partial pressure (PO2) similar to 3 3 mmHg] elicited a biphasic response in arteries precontracted with pr ostaglandin F-2 alpha (10 mu M). A transient contraction reaching a pe ak within 2-3 min was observed in both large and small pulmonary and m esenteric arteries (phase 1). In pulmonary arteries, this was followed by a slowly developing contraction over 45 min (phase 2). In mesenter ic arteries, there was no phase 2 but instead a profound relaxation. M echanical disruption of the endothelium had no significant effect on p hase 1 in preconstricted large pulmonary arteries but reduced phase 1 in small arteries by 40%. Phase 2 was abolished in both large and smal l arteries. Inhibition of endothelium-derived relaxing factor synthesi s or cyclooxygenase pathways had no effect on either phase. Verapamil substantially reduced phase 1 but abolished phase 2. In conclusion, we have found a clear biphasic response to hypoxia in pulmonary arteries of the rat, but, in contrast to some previous reports, phase 1 was on ly partially dependent on the endothelium, whereas phase 2 was entirel y dependent on the endothelium. Small and large arteries had qualitati vely similar responses. These results are consistent with the involvem ent of at least two mechanisms for hypoxic vasoconstriction, one of wh ich may involve release of an as yet unidentified endothelium-derived constrictor factor.