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`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 loM 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 1o-8 and 10-7 M PDBu infused through the donor segment. The inactive phorbol ester 4ca'phorbol 12,13-didecanoate had no effect on vascular preparations mounted in the bioassay system. Selective exposure of the bioassay tissue to 10M 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. (Circulation Research 1991;68:1527-1531)