renoreceptors. However, the fact that yohimbine had no effect whatsoever does serve to rule out involvement of this receptor type. We have shown that a nonpressor dose of ANG II infusion (25 ng kg-1 min-1) for 2 wk downregulates AT1 mRNA levels in both the aorta and mesenteric resistance arteries.This homologous downregulation of the AT1 receptor in the vascular tissue seems to be mediated by both transcriptional and posttranscriptional mechanisms. The results from the present study showed that the changes in AT1 receptor density parallel the changes in AT1 mRNA levels in cultured VSMC, indicating that NE-mediated downregulation of AT1 receptors occurs, at least partially, via a diminished AT1 receptor mRNA level. Although it is unknown whether NE-induced heterologous downregulation of AT1 receptors occurs at transcriptional or posttranscriptional levels, the data represent a clear example of cross talk between the two plasma membrane receptors.The physiological and pathophysiological significance of NE on AT1 receptor expression in the circulatory system of the rats is that the vascular AT1 receptor is a central component of the renin-angiotensin system, and regulation of its expression is likely to be important in cardiovascular responsiveness. a positive interaction between ANG II and NE through an action on the vascular AT1 and 1-adrenergic receptor to produce a greater vasoconstriction than that produced by either alone. At the same time, persistent increased ANG II and NE will downregulate the AT1 receptor, providing a "negative feedback" mechanism to attenuate the action of ANG II. Thus cyclic upregulation of ANG II and NE, a "feed-forward" mechanism, followed by downregulation of AT1 receptor by a negative feedback mechanism may play an important homeostatic role between the renin-angiotensin and sympathetic nervous systems in blood pressure regulation in the normotensive rat. Conversely, in hypertensive rats, disrupti...
