From the Department of Pharmacology, New York Medical College, Valhalla,
NY.
Correspondence to Alberto Nasjletti, MD, Department of Pharmacology, New York Medical College, Valhalla, NY 10595.
Abstract—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 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
PGH2 to PGI2 by aortic segments, the release of
6-keto-PGF1
© 1998 American Heart Association, Inc.
Scientific Contributions
Prostaglandin I2 Contributes to the Vasodepressor Effect of Baicalein in Hypertensive Rats
by aortic rings, the concentration of
6-keto-PGF1 in blood, and the renal excretion of
6-keto-PGF1. 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--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--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 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 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.
Key Words: angiotensin II • prostaglandin I2 • prostacyclin synthase • 12-lipoxygenase • lipoxygenase inhibitors
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