Prostaglandin I 2 Contributes to the Vasodepressor Effect of Baicalein in Hypertensive Rats

Abstract

Abstract —Lipoxygenase inhibitors reduce blood pressure in hypertensive rats. The vasodepressor effect of lipoxygenase inhibitors may be related to increased production of prostaglandin (PG) I 2 since lipoxygenase-derived fatty acid hydroperoxides inhibit PGI 2 synthase. This hypothesis was examined in rats made hypertensive by infusion of angiotensin II (200 ng/min IP) for 12 to 14 days. In hypertensive but not in normotensive rats, the lipoxygenase inhibitor baicalein (60 mg/kg SC) increased ( P <.05) the conversion of exogenous PGH 2 to PGI 2 by aortic segments, the release of 6-keto-PGF 1α by aortic rings, the concentration of 6-keto-PGF 1α in blood, and the renal excretion of 6-keto-PGF 1α . Treatment with baicalein did not affect the blood pressure of normotensive rats but decreased the blood pressure of hypertensive rats from 177±8 to 133±9 mm Hg after 120 minutes ( P <.05). Also, the lipoxygenase inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (8 mg/kg SC) was without effect on the blood pressure of normotensive rats but decreased the blood pressure of hypertensive rats from 182±4 to 139±8 mm Hg ( P <.05). However, the blood pressure of hypertensive rats pretreated with indomethacin (5 mg/kg IV) was affected by neither baicalein nor cinnamyl-3,4-dihydroxy-α-cyanocinnamate. Moreover, in hypertensive rats in which baicalein had decreased blood pressure to 148±6 mm Hg, the administration of rabbit serum containing antibodies against 5,6-dihydro-PGI 2 (0.3 mL IV) partially reversed the response to baicalein, increasing blood pressure to 179±7 mm Hg within 20 minutes ( P <.05). The antibodies also were shown to block the vasodepressor effect of PGI 2 but not of PGE 2 . Collectively, these data suggest contribution of PGI 2 to the acute antihypertensive effect of baicalein in rats with angiotensin II–induced hypertension.