Glucocorticoids activate cardiac mineralocorticoid receptors in adrenalectomized Dahl salt-sensitive rats.

Masafumi Ohtake, Takuya Hattori, Tamayo Murase, Keiji Takahashi, Miwa Takatsu, Mayuko Ohtake, Masaaki Miyachi, Shogo Watanabe, Xian Wu Cheng, Toyoaki Murohara, Kohzo Nagata

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)59-72
Number of pages14
JournalNagoya journal of medical science
Volume76
Issue number1-2
Publication statusPublished - Feb 2014
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Glucocorticoids activate cardiac mineralocorticoid receptors in adrenalectomized Dahl salt-sensitive rats.'. Together they form a unique fingerprint.

  • Cite this

    Ohtake, M., Hattori, T., Murase, T., Takahashi, K., Takatsu, M., Ohtake, M., Miyachi, M., Watanabe, S., Cheng, X. W., Murohara, T., & Nagata, K. (2014). Glucocorticoids activate cardiac mineralocorticoid receptors in adrenalectomized Dahl salt-sensitive rats. Nagoya journal of medical science, 76(1-2), 59-72.