Signaling mediated by the angiotensin (Ang) II and α1-adrenergic receptor (α1-AR) pathways is important for cardiovascular homeostasis. However, it is unknown whether Ang II has any direct effect on α1-AR expression and signaling in cardiac myocytes. In the present study, we determined α1-AR subtype mRNA levels by RNase protection; receptor density by competition binding with 5-methylurapidil; and α1-AR-mediated c-fos expression by Northern blot analysis. We found that Ang II had no effect on α(1b)- and α(1a)-AR mRNA levels but decreased the α(1a)-AR mRNA level in a time- and dose-dependent manner. The maximal effect occurred at 6 hours with 100 nmol/L Ang II (40.0±8.2% reduction, n=4, P<.01). The decrease in α(1a)- AR mRNA level induced by Ang II is mediated by the Ang II AT1 receptor subtype and is associated with decreased stability of α(1a)-AR mRNA. Corresponding to the changes in the α(1a)-AR mRNA level, Ang II (100 nmol/L, 24 hours) reduced the density of high-affinity sites for 5-methylurapidil (α(1A)-AR) by 29% (56.5±6.4 versus 79.0±11.6 fmol/mg protein, n=4, P<.05). α1-AR-stimulated c-fos induction, which could be blocked by 5- methylurapidil but not by chloroethylclonidine, was attenuated by Ang II preincubation (100 nmol/L, 24 hours). We conclude that there is previously undescribed cross talk between AT1 receptors and α1-ARs. Ang II selectively downregulates α(1a)-AR subtype mRNA and its corresponding receptor as well as α(1a)-AR-mediated expression of the immediate-early gene c-fos in cardiac myocytes.