This study determined the effect of phorbol pretreatment on serotonin [5-hydroxytryptamine (5-HT)]-induced contractions of rabbit abdominal aorta. Rings of aorta pretreated with 12-O-tetradecanoylphorbol 13-acetate (TPA, 10(-7) M) contracted more strongly (P less than 0.01) than rings pretreated with the vehicle dimethyl sulfoxide (0.0007%), but only at low 5-HT concentrations (10(-8) to 10(-7) M). A 10-min exposure to TPA (10(-7) M) increased (P less than 0.01) 5-HT contractions (10(-7) M) from 23.7 +/- 2.6 to 42.1 +/- 4.5%. This amplification required an intact endothelium and the use of a biologically active phorbol. Pretreatment with TPA (10(-7) M) reduced (P less than 0.01) acetylcholine-induced relaxations from 56.6 +/- 6.6 to 20.0 +/- 13.8%. Changes in guanosine 3',5'-cyclic monophosphate-mediated relaxation are not involved in this decrease, since relaxations to sodium nitroprusside (10(-9) to 10(-8) M) were not altered by TPA pretreatment. These results suggest that activation of protein kinase C in endothelial cells may produce arterial supersensitivity to 5-HT by decreasing the release of endothelium-derived relaxing factor(s) and/or by increasing the release of endothelium-derived contracting factor(s).
- Copyright © 1989 the American Physiological Society