title: Angiotensin-II-induced enhanced expression of Gi proteins is attenuated by losartan in A10 vascular smooth muscle cells: role of AT1 receptors.
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 (Gi alpha2 and Gi alpha3). In the present studies, we have investigated the role of type 1 angiotensin receptors (AT1) in the Ang-II-induced enhanced expression of Gi alpha proteins and their functions in A10 SMCs. Ang II enhanced the levels of Gi alpha2 and Gi alpha3 proteins and their mRNA, as determined by Western and Northern blot analysis, respectively; losartan treatment attenuated the enhanced expression of Gi alpha2 and Gi alpha3 proteins 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)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 AT1 receptors in Ang-II-evoked increases in Gi alpha protein expression and Gs-mediated stimulation in VSMCs.
authors.affiliation: Department of Physiology and Groupe de recherche sur le système nerveux autonome, Faculty of Medicine, University of Montreal, C.P. 6128, Succ. centre-ville, Montréal, QC H3C 317, Canada. anandsrm@physio.umontreal.ca
authors.forename: Madhu B
authors.initials: MB
authors.lastname: Anand-Srivastava
authors.forename: Anuradha
authors.initials: A
authors.lastname: Palaparti
mesh_terms: D000262:Adenylyl Cyclases / Q000737:chemistry; D000804:Angiotensin II / Q000187:drug effects* / Q000235:genetics*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D015151:Immunoblotting; D019808:Losartan / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D009154:Mutation; D012313:RNA / Q000302:isolation & purification*; D051381:Rats; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D012313:RNA; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D000262:Adenylyl Cyclases; D019808:Losartan