MYOCARDIAL PRODUCTION OF ALDOSTERONE AND CORTICOSTERONE IN THE RAT - PHYSIOLOGICAL REGULATION

Increasing evidence suggests that mineralo- and glucocorticoids modula te cardiovascular homeostasis via the effects of circulating component s generated within the adrenals but also through local synthesis, The aim of this study was to assess the existence of such a steroidogenic system in heart, Using the quantitative reverse transcriptase-polymera se chain reaction, the terminal enzymes of corticosterone and aldoster one synthesis (11 beta-hydroxylase and aldosterone synthase, respectiv ely) were detected in the rat heart, This pathway was shown to be phys iologically active, since production of aldosterone, corticosterone, a nd their precursor, deoxycorticosterone, was detected in both the homo genate and perfusate of isolated rat hearts using radioimmunoassay aft er Celite column chromatography, Perfusion of angiotensin II or adreno corticotropin for 3 h increased aldosterone and corticosterone product ion and decreased deoxycorticosterone, suggesting that aldosterone and corticosterone are formed within the isolated heart from a locally pr esent substrate, Chronic regulation of this intracardiac system was th en examined, As in adrenals cardiac 11 beta-hydroxylase and aldosteron e-synthase mRNAs were independently regulated by 1 week's treatment wi th either low sodium and high potassium diet (which increased aldoster one synthase mRNA level only), angiotensin II (which raised level of b oth mRNAs), or adrenocorticotropin (which stimulated the 11 beta-hydro xylase gene exclusively). Changes in cardiac steroid levels during tre atment were not directly related to their plasma levels suggesting ind ependent regulating mechanisms, This study, therefore, provides the fi rst evidence for the existence of an endocrine cardiac steroidogenic s ystem in rat heart and emphasizes its potential physiological and path ological relevance.