Journal of Pharmacy and Pharmacology
Hariane Côco, Larissa Pernomian, Priscila C. Pereira, Mayara S. Gomes, Katia C. Marchi, Alexandre H. Lopes, Thiago M. Cunha, Carlos R. Tirapelli, Ana M. de Oliveira
To investigate the mechanisms underlying the effects of chronic restraint stress on the vascular contractile response induced by angiotensin (Ang) II in rat carotid.
Concentration–response curves for AngII were obtained in endothelium-intact or endothelium-denuded carotid rings, in the absence or presence of SC-560 (COX-1 inhibitor), SC-236 (COX-2 inhibitor), wortmannin (PI3K-Akt inhibitor), ML171 (NOX-1 inhibitor), VAS2870 (NOX-4 inhibitor), tiron (math formula scavenger) or PEG-catalase (H2O2 scavenger). 6-ketoPGF1α, TXB2, math formula or H2O2 levels and superoxide dismutase and catalase activity or expression were also measured in rat carotid.
Stress increased AngII potency in rat carotid. Muscular COX-1 or COX-2-derived metabolites negatively modulated AngII-induced contraction in control rat carotid. Endothelial COX-1 or COX-2-derived metabolites positively modulated AngII-induced contraction in stressed rat carotid. PI3K-Akt, NOX-1, NOX-4, math formula and H2O2 positively modulated AngII-induced contraction in stressed rat carotid. Stress increased 6-ketoPGF1α or H2O2 generation and reduced catalase activity in rat carotid. Protein expression of COX-1, NOX-4 or p-Akt was increased in stressed rat carotid.
Stress increases AngII potency in rat carotid by a mechanism that involves the increased generation of PGI2 and H2O2 and the activation of Akt pathway. Such mechanism could play a pathophysiological role in cardiovascular diseases correlated with stress.