Genistein treatment reduces arterial contractions by inhibiting tyrosine kinases in ovariectomized hypertensive rats.
The aim of the present study was to evaluate the vascular effects of genistein in a short-term study. The ovariectomized spontaneously hypertensive rats (SHR) were divided into four groups (n = 8 in each), which received the following subcutaneous treatments either for 2 days or for 2 weeks: (1) solvent control (96% dimethylsulphoxide (DMSO) 1 ml/kg), (2) estradiol-17beta (25 microg/kg), (3) genistein (2.5 mg/kg; low-dose), and (4) genistein (25 mg/kg; high-dose). The renal arterial rings were studied using organ bath system. The renal artery contractions were attenuated by the 2-day low-dose genistein treatment as follows: angiotensin II (46%), noradrenaline (42%) KCl (36%), and endothelin-1 (34%). Only the angiotensin II-induced contractions were reduced by the 2-week treatment with estradiol-17beta (38%) and with the low-dose of genistein (31%). The 2-day genistein treatment reduced tyrosine phosphorylation, while the other treatments or treatment times had no effect. The 2-day low-dose genistein treatment had no estrogenic effect on the uterine morphology. The mechanism for attenuated contractility in the renal arteries after the 2-day low-dose genistein treatment is independent of the estrogenic effect of genistein, but is due to the tyrosine kinase inhibitory property of genistein.
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D004435:Eating / Q000187:drug effects; D004573:Electrolytes / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism; D014599:Uterus / Q000187:drug effects
D004573:Electrolytes; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D014443:Tyrosine; D004958:Estradiol; D003404:Creatinine; D019833:Genistein; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D011505:Protein-Tyrosine Kinases