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 micrograms, 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 microM. The verapamil concentration that inhibited 50% of LVR response (ED50) to 5-HT was 12.1 +/- 5.5 microM. The LVR response to 50, 100, and 250 micrograms 5-HT was reduced after 12.5 microM verapamil by 41 +/- 4.4, 43 +/- 3.8, and 43 +/- 5.0%, respectively. The increase in Ra to 50, 100, and 250 micrograms 5-HT was reduced by 57 +/- 6.7, 57 +/- 4.6, and 51 +/- 7.2%, respectively, by 12.5 microM verapamil, with Rv reduced by 32 +/- 3.9% only at 250 micrograms 5-HT. The alpha-adrenergic receptor antagonist, phentolamine (10 microM) reduced the pressor response to norepinephrine (NE) by 97% but reduced the Ppa increase to 250 micrograms 5-HT by only 29 +/- 10% and did not alter the pressor response to 5 mmol KCl. A verapamil concentration of 105 microM was required to inhibit 50% of the control pressor response to KCl. Our results suggest that the entry of extracellular calcium is important for 5-HT-evoked contractions of canine pulmonary vascular smooth muscle.
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000.
H A
HA
el-Kashef
W F
WF
Hofman
I C
IC
Ehrhart
D000818:Animals; D004285:Dogs; D005260:Female; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D012702:Serotonin Antagonists; D012701:Serotonin; D011189:Potassium Chloride; D014700:Verapamil; D010646:Phentolamine