The aims of this study were to search for the role of cholic acid in the regulation blood pressure of humans and rats and to investigate the effects of cholic acid on the production of vascular aldosterone and corticosterone in rats. Levels of serum total bile acids were measured by an enzymic spectrophotometeric method in normal controls, patients with essential hypertension, and in Wistar and spontaneously hypertensive rats. Levels in essential hypertension (7.3+/-3.4 micromol/l, n = 88) were higher than those of normal subjects (4.9+/-3.3 micromol/l, n = 86), and levels in SHR (13.9+/-3.8 micromol/l, n = 11) were slightly increased, but not significantly different from Wistar rats (10.4+/-5.1 micromol/l, n = 12). Male Wistar rats received cholic acid 80 mg/kg/day, orally, for 30 days, and blood pressure was monitored by a pressure transducer. Systolic blood pressure increased in Wistar rats treated with cholic acid compared to control rats. Mesenteric artery perfusion ex vivo was performed, and pressor responses to norepinephrine were determined in Wistar rats. The pressor responses to norepinephrine in mesenteric arteries treated with cholic acid were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column for reverse phase high performance liquid chromatography, and levels of both aldosterone and corticosterone were determined by radioimmunoassay. Levels of aldosterone were decreased but those of corticosterone increased in the perfusate from arteries treated with cholic acid. Reverse transcriptase polymerase chain reaction showed that cholic acid inhibited the expression of 11beta-HSD2 and CYP11B2 mRNA in mesenteric arteries. These results reveal that cholic acid is able to induce hypertension and provide evidence that cholic acid inhibits the transcription of both 11beta-HSD2 and CYP11B2 in vasculature, leading to lower aldosterone and higher corticosterone production in vessels and increased vasoconstrictor responses to norepinephrine.