INCREASED ANGIOTENSIN-II TYPE-1 RECEPTOR GENE-EXPRESSION IN NEURONAL CULTURES FROM SPONTANEOUSLY HYPERTENSIVE RATS

In this study we compared the expression of angiotensin II type 1 (AT1) receptor messenger RNA (mRNA) and AT1 receptors in neurons cultured from Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rat brains. Neuronal cultures from the hypothalamus and brain-stem of 1-day-old SH rats exhibited approximately 4-fold higher steady-state levels of AT1 receptor mRNA than the corresponding WKY cultures. This was attributable to greater levels of both AT1A and AT1B receptor mRNA subtypes in SH rat neuronal cultures compared with WKY rat neurons. SH rat neuronal cultures also exhibited increased numbers (approximately 2.3-fold) of binding sites for [H-3]DuP753, an AT1 receptor selective ligand, and enhanced (approximately 3.4-fold) stimulation of inositol phospholipid hydrolysis by angiotensin II compared with WKY neurons. By contrast, cultured astroglia from SH and WKY rat brain exhibited no significant differences in either the levels of AT, receptor mRNA or the specific binding of [H-3]DuP753. These data suggest that in SH rat neurons, AT1 receptor transcription and translation is increased, compared with neurons from WKY rats.