Chronic restraint stress increases angiotensin II potency in the rat carotid: role of cyclooxygenases and reactive oxygen species.

Objectives: To investigate the mechanisms underlying the effects of chronic restraint stress on the vascular contractile response induced by angiotensin (Ang) II in rat carotid.
Methods: 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 (PI ₃ K-Akt inhibitor), ML171 (NOX-1 inhibitor), VAS2870 (NOX-4 inhibitor), tiron (O2- scavenger) or PEG-catalase (H ₂ O ₂ scavenger). 6-ketoPGF _1α , TXB ₂ , O2- or H ₂ O ₂ levels and superoxide dismutase and catalase activity or expression were also measured in rat carotid.
Key Findings: 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. PI ₃ K-Akt, NOX-1, NOX-4, O2- and H ₂ O ₂ positively modulated AngII-induced contraction in stressed rat carotid. Stress increased 6-ketoPGF _1α or H ₂ O ₂ generation and reduced catalase activity in rat carotid. Protein expression of COX-1, NOX-4 or p-Akt was increased in stressed rat carotid.
Conclusions: Stress increases AngII potency in rat carotid by a mechanism that involves the increased generation of PGI ₂ and H ₂ O ₂ and the activation of Akt pathway. Such mechanism could play a pathophysiological role in cardiovascular diseases correlated with stress.
(© 2016 Royal Pharmaceutical Society.)