title: Estrogen receptor agonists alleviate cardiac and renal oxidative injury in rats with renovascular hypertension.
abstract: Although endogenous estrogen is known to offer cardiac and vascular protection, the involvement of estrogen receptors in mediating the protective effect of estrogen on hypertension-induced cardiovascular and renal injury is not fully explained. We aimed to investigate the effects of estrogen receptor (ER) agonists on oxidative injury, cardiovascular and renal functions of rats with renovascular hypertension (RVH). Female Sprague-Dawley rats were randomly divided as control and RVH groups, and RVH groups had either ovariectomy (OVX) or sham-OVX. Sham-OVX-RVH and OVX-RVH groups received either ERβ agonist diarylpropiolnitrile (1 mg/kg/day) or ERα agonist propyl pyrazole triol (1 mg/kg/day) for 6 weeks starting at the third week following the surgery. At the end of the 9(th) week, systolic blood pressures were recorded, cardiac functions were determined, and the contraction/relaxation responses of aortic rings were obtained. Serum creatinine levels, tissue malondialdehyde, glutathione, superoxide dismutase, catalase levels, and myeloperoxidase activity in heart and kidney samples were analyzed, and Na(+), K(+)-ATPase activity was measured in kidney samples. In both sham-OVX and OVX rats, both agonists reduced blood pressure and reversed the impaired contractile performance of the heart, while ERβ agonist improved renal functions in both the OVX and non-OVX rats. Both agonists reduced neutrophil infiltration, lipid peroxidation, and elevated antioxidant levels in the heart, but a more ERβ-mediated protective effect was observed in the kidney. Our data suggest that activation of ERβ might play a role in preserving the function of the stenotic kidney and delaying the progression of renal injury, while both receptors mediate similar cardioprotective effects.
authors.affiliation: a Marmara University School of Medicine , Department of Physiology , Istanbul , Turkey.
authors.forename: Zarife Nigâr
authors.initials: ZN
authors.lastname: Özdemir Kumral
authors.affiliation: b Acibadem University School of Medicine , Department of Physiology , Istanbul , Turkey.
authors.forename: Meltem
authors.initials: M
authors.lastname: Kolgazi
authors.affiliation: c Bezmialem Vakıf University School of Medicine , Department of Physiology , Istanbul , Turkey.
authors.forename: Savaş
authors.initials: S
authors.lastname: Üstünova
authors.affiliation: a Marmara University School of Medicine , Department of Physiology , Istanbul , Turkey.
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Kasımay Çakır
authors.affiliation: d Cumhuriyet University Faculty of Pharmacy , Department of Biochemistry , Sivas , Turkey.
authors.forename: Özge Dağdeviren
authors.initials: ÖD
authors.lastname: Çevik
authors.affiliation: e Marmara University Faculty of Pharmacy , Department of Pharmacology , Istanbul , Turkey.
authors.forename: Göksel
authors.initials: G
authors.lastname: Şener
authors.affiliation: a Marmara University School of Medicine , Department of Physiology , Istanbul , Turkey.
authors.forename: Berrak Ç
authors.initials: BÇ
authors.lastname: Yeğen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008315:Malondialdehyde / Q000378:metabolism; D009206:Myocardium / Q000473:pathology*; D010052:Ovariectomy / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004967:Estrogens; D010636:Phenols; D020011:Protective Agents; D011720:Pyrazoles; D011960:Receptors, Estrogen; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase
keywords: Cardiac injury; estrogen receptor; menopause; oxidative stress; renal injury; renovascular hypertension