Angiotensin-II-induced enhanced expression of Gi proteins is attenuated by losartan in A10 vascular smooth muscle cells:: role of AT1 receptors

We have previously shown that treatment of A10 vascular smooth muscle cells (VSMCs) with angiotensin II (Ang II) enhanced the expression of inhibitory guanine nucleotide regulatory proteins (Gialpha(2) and Gialpha(3)). In the present studies, we have investigated the role of type 1 angiotensin receptors (AT(1)) in the Ang-II-induced enhanced expression of Gialpha proteins and their functions in A10 SMCs. Ang II enhanced the levels of Gialpha(2) and Gialpha(3) proteins and their mRNA, as determined by Western and Northern blot analysis, respectively; losartan treatment attenuated the enhanced expression of Gialpha(2) and Gialpha(3) proteins and their mRNA in a concentration-dependent manner. In addition, the inhibition of adenylyl cyclase induced by Ang II and des(Glu(18),Ser(19),Glu(20),Leu(21),Gly(22))ANP(4-23)-NH2 (C-ANP(4-23)), which was attenuated by Ang-II treatment, was partially restored by losartan treatment. Similarly, losartan was also able to restore the Ang-II-induced stimulatory responses of isoproterenol and N-ethylcarboxamide adenosine (NECA) on adenylyl cyclase activity. These results suggest a role for AT(1) receptors in Ang-II-evoked increases in Gialpha protein expression and Gs-mediated stimulation in VSMCs.