P-I-PURINOCEPTOR-MEDIATED VASODILATATION AND VASOCONSTRICTION IN HYPOXIA

1 The effects of adenosine receptor agonists were examined on isolated rings of guinea-pig pulmonary artery under normoxic and hypoxic condi tions. The rings were denuded of endothelium and tissues were precontr acted with phenylephrine (3 x 10(-6) M) before constructing cumulative concentration-response curves to the agonists. 2 5'-(N-ethylcarboxami do)adenosine (NECA) caused concentration-dependent contractions of the pulmonary artery which were not different between hypoxia and normoxi a. The contractions were converted to a relaxation in the presence of the cyclooxygenase inhibitor, indomethacin, and again these were unaff ected by hypoxia. 3 Examination of a range of agonists under normoxic conditions in the presence of indomethacin revealed relaxations, excep t for the Ala receptor-selective agonist, CGS 21680. The vasorelaxatio n was therefore A(2b) receptor-mediated. 4 In hypoxia, however, in the presence of indomethacin, vasoconstriction occurred to R(-)-N-6-(2-ph enylisopropyl)adenosine (R-PIA) and, to a greater extent, to N-6-cyclo pentyladenosine (CPA). In the absence of indomethacin, the constrictio n by CPA during hypoxia was significantly greater. 5 The indomethacin- resistant contraction by CPA was abolished by the Al receptor antagoni st, 8-cyclopentyltheophylline (CPT, 3 x 10(-6) M). 6 This study has de monstrated cyclooxygenase-dependent and -independent vasoconstrictions to adenosine agonists in guinea-pig pulmonary artery under hypoxic co nditions. The cyclooxygenase-independent contraction is mediated via A l receptors. 7 These results suggest that endogenous adenosine release d in the pulmonary circulation under hypoxic conditions will cause vas oconstriction and may contribute to the pulmonary hypertension associa ted with acute respiratory failure.