[Ca{sup 2+}]{sub i} and PKC-{alpha} are involved in the inhibitory effects of Ib, a novel nonpeptide AngiotensinII subtype AT{sub 1} receptor antagonist, on AngiotensinII-induced vascular contraction in vitro
Journal Article
·
· Biochemical and Biophysical Research Communications
- Department of Physiology, College of Pharmacy, China Pharmaceutical University, No. 24, Tong Jia Xiang Street, Nanjing 210009 (China)
- Department of Medicinal Chemistry, College of Pharmacy, China Pharmaceutical University, No. 24, Tong Jia Xiang Street, Nanjing 210009 (China)
The vasoactive peptide AngiotensinII (AngII) is an important factor in the cardiovascular system, exerting most of its effects through AngII receptor type 1 (AT{sub 1}). Ib, a new nonpeptide AT{sub 1} receptor antagonist, has been observed to play a positive role in the treatment of hypertension in preclinical tests. In this study, the inhibitory effects of Ib on AngII-induced vascular contraction in vitro were investigated, and its molecular mechanisms were further explored. In endothelium-denuded aortic rings from rabbits, Ib produced a rightward shift in the concentration-response curve for AngII with a decrease in the maximal contractile response and the pD{sub 2}{sup '} was 7.29. In vascular smooth muscle cells (VSMCs), the specific binding of [{sup 125}I]AngII to AT{sub 1} receptors was inhibited by Ib in a concentration-dependent manner with IC{sub 50} value of 0.96 nM. Ib could inhibit both AngII-induced Ca{sup 2+} mobilization from internal stores and Ca{sup 2+} influx. Moreover, the translocation of PKC-{alpha} stimulated by AngII was inhibited by Ib. Thus, the inhibitory effects of Ib might be related with the depression on AngII-induced increase in [Ca{sup 2+}]{sub i} and translocation of PKC-{alpha} through blocking AT{sub 1} receptors.
- OSTI ID:
- 21033002
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 364; ISSN BBRCA9; ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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