VERAPAMIL INHIBITION OF SEROTONIN-INDUCED VASOCONSTRICTION IN DOG LUNG

The effect of the voltage-dependent calcium channel blocker verapamil on serotonin (5-HT)-induced vasoconstriction and segmental distribution of vascular resistance was examined in isolated, blood-perfused dog left lower lung lobe. 5-HT, 250 μg, increased lobar vascular resistance (LVR) by 47.3 ± 6.5 cm H2O (n = 7), accounted for by a 30.8 ± 4.3 and 16.4 ± 2.8 cm H2O increase in upstream (Ra) and downstream (Rv) resistance, respectively. However, the increase in LVR, Ra, and Rv to 5-HT was significantly attenuated as verapamil concentration was increased from 1.2 to 100 μM. The verapamil concentration that inhibited 50% of LVR response (ED50) to 5-HT was 12.1 ± 5.5 μM. The LVR response to 50, 100, and 250 μg 5-HT was reduced after 12.5 μM verapamil by 41 ± 4.4, 43 ± 3.8, and 43 ± 5.0%, respectively. The increase in Ra to 50, 100, and 250 14 5-HT was reduced by 57 ± 6.7, 57 ± 4.6, and 51 ± 7.2%, respectively, by 12.5μMverapamil, with Rv reduced by 32 ± 3.9% only at 250 p.g 5-HT. The a-adrenergic receptor antagonist, phentolamine (10 μM) reduced the pressor response to norepinephrine (NE) by 97% but reduced the Ppa increase to 250 μg 5-HT by only 29 ± 10% and did not alter the pressor response to 5 mmol KCI. A verapamil concentration of 105 μM was required to inhibit 50% of the control pressor response to KCI. Our results suggest that the entry of extracellular calcium is important for 5-HT-evoked contractions of canine pulmonary vascular smooth muscle. © 1990 Raven Press, Ltd., New York.