The identities of the Ca2+ influx mechanisms underlying hypoxic pulmonary vasoconstriction (HPV), the contractile response of pulmonary arteries (PA) to hypoxia, remain controversial. We investigated the roles of Na+/Ca2+ exchange (NCX) and capacitative Ca2+ entry (CCE) in HPV by measuring isometric tension in rat intrapulmonary arteries (IPA) during hypoxia. It has been shown in PA cells that hypoxia raised [Ca2+]i by inhibiting NCX. We found that removal of Na+ caused a response resembling HPV, suggesting that HPV could be due to inhibition of NCX. However, prior inhibition of NCX using Na+ free solution or 3 microM KB-R7943 enhanced rather than prevented HPV, indicating that HPV is not caused by an inhibition of NCX. The CCE blocker 2-APB inhibited both phases of HPV, and the ryanodine receptor blocker dantrolene inhibited the 2nd phase of HPV. Taken together with previous observations, these results suggest a role for CCE in HPV, but suggest that different CCE pathways may be involved for each phase.
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