Role of calcium in U 46619 and PGF2 alpha pulmonary vasoconstriction in rat lungs.

The role of calcium and calmodulin during U 46619 and PGF2 alpha-induced pulmonary vasoconstriction was studied in isolated rat lungs perfused with Krebs-Ringer bicarbonate (KRB) or calcium-free KRB. In lungs perfused with KRB, bolus injections of U 46619 (0.2 microgram) and PGF2 alpha (40.0 micrograms) resulted in a 48.0 +/- 4.0 and 23.9 +/- 2.5% increase in mean pulmonary artery pressure, respectively. During lung perfusion with KRB without calcium, the U 46619 response decreased to 31.1 +/- 7.5% whereas the PGF2 alpha response increased to 34.6 +/- 4.1%. Repeated challenges with PGF2 alpha in the KRB without calcium resulted in reduction of the response to 11.8 +/- 1.2%; the U 46619 response was unaltered. The intracellular calcium blocker, 8-(N,N-diethylamino)-octyl-3,4,5, trimethoxybenzoate HCL (TMB-8) significantly attenuated the pressor response to U 46619 at low doses and PGF2 alpha at high doses. The calmodulin inhibitor trifluoperazine (TFP 100 microM) attenuated the vasoconstrictor response to U 46619 by 54%, whereas the PGF2 alpha was unchanged. However, in the calcium-free KRB, TFP attenuated the pressor response to both U 46619 and PGF2 alpha. The U 46619 pressor response depends on intracellular and extracellular calcium to achieve calmodulin-dependent vasoconstriction. PGF2 alpha requires extracellular calcium to replenish depletable intracellular calcium pools and is independent of calmodulin activation.