Bile acids (BA) and BA receptors, including G protein–coupled bile acid receptor 1 (GPBAR1), represent novel targets for the treatment of metabolic and inflammatory disorders. However, BAs have been shown to have effects on cardiovascular function. This study was designed to test whether stimulation of GPBAR1 elicits mechanism-based effects on cardiovascular function. Results demonstrate that infusion of three structurally diverse and selective GPBAR1 agonists produces marked reductions in vascular tone and blood pressure in dog but not in rat. A direct effect on vascular tone was confirmed in dog isolated vascular rings whereby concentration-dependent decreases in tension were tightly correlated with reductions in vascular tone observed in vivo and were blocked by iberiotoxin. These results are the first to clearly demonstrate direct and potent peripheral arterial vasodilation attributed to GPBAR1 stimulation in vivo through activation of KCa1.1 (BKCa).
See article at J Pharmacol Exp Ther 2014, 348:421–431.
- Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics