REGULATION OF TYPE-1 ANG-II RECEPTOR IN VASCULAR TISSUE - ROLE OF ALPHA(1)-ADRENORECEPTOR

Angiotensin II (ANG II) and norepinephrine (NE) are important regulato rs of vascular function and structure. Recent studies showed that ther e are multiple interactions between these two potent vasoconstrictor a gents. The present experiment was designed to investigate the effect o f NE on the expression of the type 1 ANG II receptor (AT(1)) in the ao rta and cultured vascular smooth muscle cells (VSMC) of rats. Rats wer e subcutaneously infused with either NE (0.5 mu g . kg(-1) . min(-1), n = 6) or the alpha(1)-adrenoreceptor antagonist prazosin (3.5 mu g . kg(-1) . min(-1), n = 6) for 2 wk. Body weight and tail cuff systolic blood pressure were not modified compared with the vehicle control (P > 0.05). Northern blot analysis showed that AT(1) mRNA levels in aorta were decreased by 38% in NE-treated rats and increased 117% in prazos in-treated rats (P < 0.05) compared with control. To determine whether NE directly regulates expression of vascular AT(1) mRNA and AT(1) rec eptor density, Northern blot analysis and radioligand binding experime nts were performed in cultured VSMC. Incubation of VSMC with NE (10(-7 ) M) led to 44% decrease in AT(1) mRNA. levels (P < 0.05) and 39% decr ease in AT(1) receptor density (P < 0.05). Prazosin, but not the alpha (2)-adrenoreceptor antagonist yohimbine, prevented NE-induced decrease in AT(1) mRNA and AT(1) receptor density in these cells. Taken togeth er, our results indicate that vascular AT(1) gene expression and recep tor protein are regulated by ambient NE levels, and NE-induced downreg ulation of AT(1) mRNA and receptor protein is mediated, at least in pa rt, by activating alpha(1)-adrenoreceptors.