Comparative effects of tamoxifen and angiotensin II type-1 receptor antagonist therapy on the hemodynamic profile of the ovariectomized female rat.
Hormonal replacement therapy (HRT) has failed to provide a cardioprotective action in postmenopausal women, and thus alternative pharmacological approaches are required. The present study examined the therapeutic potential of the partial estrogen receptor agonist tamoxifen and the angiotensin II type-1 receptor antagonist irbesartan on the hemodynamic profile of ovariectomized (OVX) female Sprague-Dawley rats (9-11 weeks). Three weeks following ovariectomy, uterine atrophy was evident and body weight was increased as compared with sham-operated animals. Left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), and mean arterial pressure (MAP) were significantly increased in the OVX rats as compared with sham rats. One week following ovariectomy, rats were treated with either tamoxifen (10 mg kg-1 day-1) or irbesartan (40 mg kg-1 day-1) for a period of 2 weeks. The administration of tamoxifen to OVX rats partially reversed uterine atrophy and prevented body weight gain, albeit body weight remained significantly lower than in sham-operated animals. LVSP and LVEDP were normalized in the tamoxifen-treated OVX rats, whereas MAP remained elevated. Irbesartan partially reduced the body weight gain of the OVX rats and did not influence uterine atrophy. LVSP and MAP were normalized in irbesartan-treated OVX rats, whereas LVEDP remained elevated. These data demonstrate that irbesartan rather than tamoxifen was efficacious in normalizing MAP in the OVX rats without a secondary effect on the uterus.
Pham-Dang
My-Lan
ML
Dept. de Physiologie, Centre de Recherche de l'Institut de Cardiologie de Montréal, Université de Montréal, 5000 est, rue Belanger, Montréal, Quebec H1T 1C8, Canada.
Clement
Robert
R
Mercier
Isabelle
I
Calderone
Angelino
A
D047228:Angiotensin II Type 1 Receptor Blockers; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D000077405:Irbesartan; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors*; D013629:Tamoxifen / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology*; D014599:Uterus / Q000033:anatomy & histology / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D011960:Receptors, Estrogen; D013777:Tetrazoles; D013629:Tamoxifen; D000077405:Irbesartan