Effects of phorbol esters on canine coronary artery constriction and dilation in vitro.
The influence of protein kinase C (PKC) activation on canine coronary vasoreactivity was assessed in vitro. Activation of PKC by phorbol 12,13-dibutyrate (PDBu) or phorbol 12-myristate 13-acetate (PMA) caused slow sustained constriction of isolated coronary artery rings. PDBu was a more potent and efficacious constrictor than PMA (169 +/- 21 vs. 81 +/- 7% of maximum KCl constriction). Constriction to PDBu was reduced slightly by deendothelialization and by meclofenamate. Pretreatment with threshold concentrations of PDBu increased constriction to serotonin from 3 +/- 1 to 48 +/- 4% of maximum KCl constriction whether or not the endothelium was present but had no effect on response to the thromboxane analogue U-46619. In addition, in arteries constricted with PDBu, dilations to ADP, thrombin, acetylcholine, and sodium nitroprusside were impaired when compared with arteries constricted with U-46619. These results suggest that activation of PKC in coronary arteries 1) produces potent constriction mediated only in small part by the endothelium and by cyclooxygenase products, 2) potentiates markedly the constrictor response to serotonin by an endothelium-independent mechanism, and 3) attenuates both endothelium-dependent and endothelium-independent vasodilation.
Sheridan
F M
FM
Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262.
Horwitz
L D
LD
McMurtry
I F
IF
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D003470:Culture Media; D004285:Dogs; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008469:Meclofenamic Acid / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D003470:Culture Media; D010703:Phorbol Esters; D014665:Vasodilator Agents; D012701:Serotonin; D015240:Phorbol 12,13-Dibutyrate; D008469:Meclofenamic Acid; D015121:6-Ketoprostaglandin F1 alpha