Prostaglandin I2 contributes to the vasodepressor effect of baicalein in hypertensive rats.
Lipoxygenase inhibitors reduce blood pressure in hypertensive rats. The vasodepressor effect of lipoxygenase inhibitors may be related to increased production of prostaglandin (PG) I2 since lipoxygenase-derived fatty acid hydroperoxides inhibit PGI2 synthase. This hypothesis was examined in rats made hypertensive by infusion of angiotensin II (200 ng/min i.p.) for 12 to 14 days. In hypertensive but not in normotensive rats, the lipoxygenase inhibitor baicalein (60 mg/kg s.c.) increased (P<.05) the conversion of exogenous PGH2 to PGI2 by aortic segments, the release of 6-keto-PGF1alpha by aortic rings, the concentration of 6-keto-PGF1alpha in blood, and the renal excretion of 6-keto-PGF1alpha. 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-alpha-cyanocinnamate (8 mg/kg s.c.) 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 i.v.) was affected by neither baicalein nor cinnamyl-3,4-dihydroxy-alpha-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-PGI2 (0.3 mL i.v.) 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 PGI2 but not of PGE2. Collectively, these data suggest contribution of PGI2 to the acute antihypertensive effect of baicalein in rats with angiotensin II-induced hypertension.
Takizawa
H
H
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
DelliPizzi
A M
AM
Nasjletti
A
A
D000804:Angiotensin II; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D011464:Epoprostenol / Q000097:blood / Q000502:physiology*; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D016859:Lipoxygenase Inhibitors; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents
D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D016859:Lipoxygenase Inhibitors; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C006680:baicalein; D011464:Epoprostenol; D001092:Arachidonate 12-Lipoxygenase