Anti-hypertensive effects of probenecid via inhibition of the α-adrenergic receptor

Probenecid has long been used in the treatment of gout. its anti-gout mechanisms consist of uric acid reuptake inhibition and the consequent facilitation of uric acid excretion. in the present study,we investigated whether probenecid could exert an anti-hypertensive effect in spontaneously hypertensive rats (shr). the noninvasive indirect tail cuff method was employed to measure blood pressure and heart rate. the administration of probenecid (50 mg/kg,ip) induced a significant systolic blood pressure (sbp) decrease,from 167 mmhg to 141 mmhg,within 120 min. in contrast,probenecid had little effect on normotensive control wistar kyoto rats (wky). the anti-hypertensive effects of probenecid are almost as potent as those of atenolol. in a further exploration of the antihypertensive mechanisms of probenecid,its effects on phenylephrine-induced blood vessel contraction were tested. our results suggest that probenecid significantly inhibited the contractions of rat aorta. this effect was also observed with endothelium-removed rat aorta,suggesting that probenecid can directly interact with the α-adrenergic receptor. moreover,probenecid inhibited the α-adrenergic-receptor-mediated activation of erk i/ii in mc3tc-e1 cells. therefore,our results indicate that probenecidmight alleviate high blood pressure in shr via inhibition of the α-adrenergic receptor and erk i/ii. copyright © 2011 by institute of pharmacology polish academy of sciences.