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(-8) 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.