Angiotensin-II-induced enhanced expression of Gi proteins is attenuated by losartan in A10 vascular smooth muscle cells: role of AT1receptors

Abstract

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 (Giα2and Giα3). In the present studies, we have investigated the role of type 1 angiotensin receptors (AT1) in the Ang-II-induced enhanced expression of Giα proteins and their functions in A10 SMCs. Ang II enhanced the levels of Giα2and Giα3proteins and their mRNA, as determined by Western and Northern blot analysis, respectively; losartan treatment attenuated the enhanced expression of Giα2and Giα3proteins and their mRNA in a concentration-dependent manner. In addition, the inhibition of adenylyl cyclase induced by Ang II and des(Glu18,Ser19,Glu20,Leu21,Gly22)ANP4–23-NH2(C-ANP4–23), 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 AT1receptors in Ang-II-evoked increases in Giα protein expression and Gs-mediated stimulation in VSMCs.Key words: angiotensin II, AT1receptor, Gi proteins, adenylyl cyclase, losartan, A10 smooth muscle cells.