HYPOXIC INTRACELLULAR CA2+ IN PULMONARY-ARTERIES - EVIDENCE FOR PKC-INDEPENDENT CA2+ SENSITIZATION

The effect of hypoxia on intracellular Ca2+ ([Ca2+](i)) and tension in small intrapulmonary arteries (IPA) of the rat was examined using the Ca2+ fluorophore fura 2. Induction of hypoxia in IPA preconstricted with 3 mu M prostaglandin F-2 alpha (PGF(2 alpha)) resulted in a biphasic contractile response, the first phase of which was associated with a transient rise in [Ca2+](i). No additional rise in [Ca2+](i) was observed during the more slowly developing second phase constriction. Upon reoxygenation [Ca2+](i) and tension returned to prehypoxic levels. Ro-31-8220 [a specific protein kinase C (PKC) inhibitor] reduced the first phase in IPA preconstricted with PGF(2 alpha) or 20 mM KCl, but had no effect on the second phase constriction in either of these groups. These results demonstrate that the first phase of the hypoxic constriction is associated with a transient rise in [Ca2+](i), via either Ca2+ influx and/or release, and may have a PKC-dependent component, whereas the second phase involves a PKC-independent sensitization of the contractile machinery to Ca2+.