Vasorelaxant effects of short chain fatty acid salts in rat caudal artery

Acetate relaxes rat caudal artery and increases tissue adenosine 3',5'-cyclic monophosphate (cAMP) levels. The present study's purpose was to determine whether related ultrashort chain (volatile) fatty acids, propionate (C3), butyrate (C4), and octanoate (C8) would do so as well. It was found that butyrate and propionate had very similar vasorelaxant profiles to acetate; they relaxed caudal artery strips precontracted with KCl, phenylephrine, arginine vasopressin, and prostaglandin F2 alpha. The vasorelaxation was endothelium independent, was not blocked by indomethacin, and was associated with a rise in tissue cAMP levels but not in guanosine 3',5'-cyclic monophosphate (cGMP) levels. The mean effective concentration for butyrate (0.8 mM) was lower than that for acetate (2.0 mM) or propionate (1.9 mM). Propionate-mediated relaxation was blocked by the stilbene inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). Vasorelaxant effects of octanoate were also not dependent on endothelium and were not affected by indomethacin. Maximal vasorelaxant effect of octanoate was greater than that of acetate, propionate, or butyrate; vasorelaxant effect of octanoate was only slightly attenuated by DIDS and was associated with only a minimal effect on tissue cAMP levels. Results suggest that vasodilatory effects of acetate generalize to propionate and butyrate, but that vasorelaxant effects of octanoate may be occurring via a separate mechanism.