title: Glucocorticoids activate cardiac mineralocorticoid receptors in adrenalectomized Dahl salt-sensitive rats.
abstract: We previously showed that selective mineralocorticoid receptor (MR) blockade by eplerenone is cardioprotective in Dahl salt-sensitive (DS) rats. To clarify the consequences of glucocorticoid-mediated MR activation in these animals, we investigated the effects of exogenous corticosterone on blood pressure as well as cardiac remodeling and function after adrenalectomy. DS rats were subjected to adrenalectomy at 6 weeks of age and thereafter fed a high-salt diet and administered corticosterone (20 mg/kg per day) or vehicle. Systolic blood pressure was higher in the corticosterone group than in the vehicle group at 7 weeks and thereafter. By 11 weeks, corticosterone had reduced left ventricular (LV) mass and induced LV diastolic dysfunction. The ratio of collagen type I to type III mRNA levels in the left ventricle was increased in the corticosterone group compared with the vehicle group. Administration of a non-antihypertensive dose of the MR antagonist spironolactone (20 mg/kg per day) from 6 weeks inhibited the effects of corticosterone on both the collagen type I to type III mRNA ratio and diastolic function without affecting the decrease in LV mass. Spironolactone attenuated both the increase in NADPH oxidase activity in the left ventricle and coronary vascular inflammatory responses apparent in the corticosterone group. These results indicate that exogenous glucocorticoids induce hypertension, cardiac remodeling, and diastolic dysfunction in adrenalectomized DS rats fed a high-salt diet. The cardiac effects of exogenous glucocorticoids are likely attributable, at least in part, to myocardial oxidative stress and coronary vascular inflammation induced by glucocorticoid-activated MRs.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ohtake
authors.forename: Takuya
authors.initials: T
authors.lastname: Hattori
authors.forename: Tamayo
authors.initials: T
authors.lastname: Murase
authors.forename: Keiji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Miwa
authors.initials: M
authors.lastname: Takatsu
authors.forename: Mayuko
authors.initials: M
authors.lastname: Ohtake
authors.forename: Masaaki
authors.initials: M
authors.lastname: Miyachi
authors.forename: Shogo
authors.initials: S
authors.lastname: Watanabe
authors.forename: Xian Wu
authors.initials: XW
authors.lastname: Cheng
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.forename: Kohzo
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000633:toxicity*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000633:toxicity*; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D018161:Receptors, Mineralocorticoid / Q000819:agonists* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D017673:Sodium Chloride, Dietary; D013148:Spironolactone / Q000494:pharmacology; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D005938:Glucocorticoids; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D017673:Sodium Chloride, Dietary; D013148:Spironolactone; D019255:NADPH Oxidases; D003345:Corticosterone