Phytoestrogen genistein decreases contractile response of aortic artery in vitro and arterial blood pressure in vivo
Abstract
AIM:
To determine the mechanisms of effects of phytoestrogen genistein on the contracted rabbit aortic arteries in vitro, and observe the effect of genistein and 17-beta estradiol on mean arterial pressure (MAP) in ovariectomized (OVX) rats.
METHODS:
(1) Strips of rabbit aortic smooth muscle were suspended in organ baths containing Kreb's solution, and then isometric tension was measured. (2) Female mature Wistar rats underwent a bilateral ovariectomy (OVX). Sham-operated rats (SHAM) were used as controls. After administration of genistein (0.4 mg.kg(-1).d(-1), s.c.), 17-beta-estradiol (1 mg.kg(-1).d(-1), s.c.) or their vehicle sesame oil for 21 d, MAP was measured.
RESULTS:
(1) Similar to 17-beta-estradiol, genistein could dose-dependently relax 40 mmol/L KCl-precontracted arterial strips. Incubation with N omega-L-nitro-arginine (L-NNA), methylene blue (MB), indomethacin, propranolol or endothelium removal did not affect relaxation induced by genistein. In calcium-free solution containing 0.01 mmol/L egtazic acid (EGTA), genistein inhibited not only the first phase contraction induced by noradrenaline (NA), but also the second contraction induced by CaCl2. In addition, genistein could reduce the contractile responses of NA, KCl and CaCl2, and shift their cumulative concentration-response curves rightward. (2) MAP in OVX rats was significantly higher compared with that of SHAM rats. However, after chronically treatment with genistein or 17-beta estradiol for 21 d the baseline MAP in OVX rats was reduced significantly.
CONCLUSIONS:
(1) The vasodilator effect of genistein in vitro is endothelium independent and not related to the nitric oxide, its mechanisms being probably due to inhibition of Ca2+ influx through calcium channels in a noncompetitive manner and Ca2+ release from intracellular store induced by NA. (2) Administration of genistein or 17-beta estradiol can chronically decrease MAP in OVX rats.
Keywords:
To determine the mechanisms of effects of phytoestrogen genistein on the contracted rabbit aortic arteries in vitro, and observe the effect of genistein and 17-beta estradiol on mean arterial pressure (MAP) in ovariectomized (OVX) rats.
METHODS:
(1) Strips of rabbit aortic smooth muscle were suspended in organ baths containing Kreb's solution, and then isometric tension was measured. (2) Female mature Wistar rats underwent a bilateral ovariectomy (OVX). Sham-operated rats (SHAM) were used as controls. After administration of genistein (0.4 mg.kg(-1).d(-1), s.c.), 17-beta-estradiol (1 mg.kg(-1).d(-1), s.c.) or their vehicle sesame oil for 21 d, MAP was measured.
RESULTS:
(1) Similar to 17-beta-estradiol, genistein could dose-dependently relax 40 mmol/L KCl-precontracted arterial strips. Incubation with N omega-L-nitro-arginine (L-NNA), methylene blue (MB), indomethacin, propranolol or endothelium removal did not affect relaxation induced by genistein. In calcium-free solution containing 0.01 mmol/L egtazic acid (EGTA), genistein inhibited not only the first phase contraction induced by noradrenaline (NA), but also the second contraction induced by CaCl2. In addition, genistein could reduce the contractile responses of NA, KCl and CaCl2, and shift their cumulative concentration-response curves rightward. (2) MAP in OVX rats was significantly higher compared with that of SHAM rats. However, after chronically treatment with genistein or 17-beta estradiol for 21 d the baseline MAP in OVX rats was reduced significantly.
CONCLUSIONS:
(1) The vasodilator effect of genistein in vitro is endothelium independent and not related to the nitric oxide, its mechanisms being probably due to inhibition of Ca2+ influx through calcium channels in a noncompetitive manner and Ca2+ release from intracellular store induced by NA. (2) Administration of genistein or 17-beta estradiol can chronically decrease MAP in OVX rats.