Phorbol dibutyrate stimulates the release of diffusible endothelium-derived vasoconstrictor factor(s) from canine femoral arteries.
The purpose of this study was to analyze the effect of the tumor-promoting phorbol ester 12,13-dibutyrate (PDBu) on the synthesis/release of nonprostanoid endothelium-derived vasoactive factors. In bioassay experiments (in the presence of 10(-5) M indomethacin), infusion of PDBu (10(-9)-10(-7) M) through a femoral artery (donor) segment with endothelium evoked further, concentration-dependent contraction of superfused canine coronary artery bioassay rings without endothelium (already contracted with 10(-7) M PDBu). Removal of the endothelium from the donor segment abolished further contractions of the bioassay ring to 10(-9) M PDBu and significantly depressed the contractile responses to 10(-9) and 10(-7) M PDBu infused through the donor segment. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate had no effect on vascular preparations mounted in the bioassay system. Selective exposure of the bioassay tissue to 10(-7) M PDBu completely inhibited its responsiveness to basally released endothelium-derived relaxing factor. These data indicate that PDBu stimulates the release of a diffusible and bioassayable vasoconstrictor mediator(s) from the endothelium of canine femoral arteries.
Rubanyi
G M
GM
Department of Pharmacology, Berlex Laboratories, Inc., Cedar Knolls, N.J.
Luisi
A
A
Johns
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000502:physiology; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D014661:Vasoconstriction
D016232:Endothelins; D011450:Prostaglandin Endoperoxides, Synthetic; D015240:Phorbol 12,13-Dibutyrate; D000109:Acetylcholine