ALTERED AGE-DEPENDENT MODULATION OF TISSUE RENIN MESSENGER-RNA LEVELSIN THE SPONTANEOUSLY HYPERTENSIVE RAT

Objective To evaluate the possible role of tissue renin overproduction in the pathogenesis and time course of hypertension development in th e spontaneously hypertensive rat (SHR) of the Okamoto strain by measur ing tissue renin gene expression at different stages of hypertension d evelopment. Design Measurements of kidney, adrenal gland and brain ste m renin messenger RNA(mRNA) levels were performed in SHR aged 4, 12, 2 0 and 36 weeks and in age-matched normotensive Wistar-Kyoto (WKY) rats . Methods A fully quantitative, competitive reverse transcriptase poly merase chain reaction method was used to measure tissue renin mRNA lev els, Plasma renin concentrations were measured by radioimmunoassay. Re sults Compared with age-matched WKY rats, renin mRNA levels in the adr enal gland of SHR were significantly higher at ages 4, 12 and 36 weeks , Brain stem renin mRNA levels were significantly higher in SHR than i n WKY rats at ages 4, 12 and 20 weeks. In contrast, renal renin mRNA l evels were consistently lower in SHR at all ages, as were plasma renin concentrations. Conclusions The present study indicates an important role for renin gene expression both in adrenal and in brain stem tissu es in the pathogenesis of hypertension in SHR, Adrenal and brain renin -angiotensin systems may interact with each other synergistically in t he development and maintenance of hypertension in SHR, Suppressed rena l renin gene expression could then be an indirect consequence of the a mplified renin-angiotensin system in the adrenal gland and in the brai n or a baroreceptor-mediated consequence of its hypertension.