Regulation of type 1 ANG II receptor in vascular tissue: role of alpha(1)-adrenoreceptor

Angiotensin II (ANG II) and norepinephrine (NE) are important regulators of vascular function and structure. Recent studies showed that there are multiple interactions between these two potent vasoconstrictor agents. The present experiment was designed to investigate the effect of NE on the expression of the type 1 ANG II receptor (AT(1)) in the aorta and cultured vascular smooth muscle cells (VSMC) of rats. Rats were 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 prazosin-treated rats (P < 0.05) compared with control. To determine whether NE directly regulates expression of vascular AT(1) mRNA and AT(1) receptor density, Northern blot analysis and radioligand binding experiments 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% decrease 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 together, our results indicate that vascular AT(1) gene expression and receptor protein are regulated by ambient NE levels, and NE-induced downregulation of AT(1) mRNA and receptor protein is mediated, at least in part, by activating alpha(1)-adrenoreceptors.