HYPOXIC CONSTRICTOR RESPONSE IN THE ISOLATED PULMONARY-ARTERY FROM CHRONICALLY HYPOXIC RATS

The aim of this study was to characterise the response to acute hypoxi a in pulmonary artery rings isolated from rats exposed to chronic hypo xia for 2 weeks (CH) and following recovery in room air for 24 h (post hypoxic, PH). Large intrapulmonary artery (IPA) rings (internal diame ter = 1.5 +/- 0.11 mm; n = 13) from CH and PH rats and age-matched con trols were studied. These were precontracted with phenylephrine using standard organ bath procedures at an oxygen tension of 152 mmHg and su bjected to an acute hypoxia stimulus (bubbling with 0% O-2 giving P-O2 = 7 mmHg or 2% O-2 giving P-O2 = 20 mmHg). Acute hypoxia-induced pulm onary vasoconstriction (HPV) consisted of a transient contraction, a r elaxation and a sustained contraction over 30 min. Pulmonary vasoconst riction induced by 0% O-2 was significantly reduced in IPA rings from the CH but not PH group compared with the response obtained from the c ontrol group. HPV induced by 2% O-2 in IPA rings from CH and PH rats w as not significantly different from that in control rats not subjected to chronic hypoxia, Mechanical removal of the endothelium or inhibiti on of nitric oxide (NO) synthase by L-NOARG (300 mu M) reduced the con tractile phases of HPV in IPA rings from control and CH rats. Carbacho l-induced endothelium-dependent relaxation in phenylephrine precontrac ted LPA rings was significantly attenuated in the CH but not PH group. In conclusion, the present study demonstrates that HPV induced by 0% O-2 in rat IPA rings was blunted in CH rats and restored following 24 h in room air, in parallel with changes in endothelium function.