Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia

Author(s)

Pereira, Priscila Cristina ^[1] ; Pernomian, Larissa ^[2] ; Coco, Hariane ^[1] ; Gomes, Mayara Santos ^[2] ; Franco, Joao Jose ^[3] ; Marchi, Katia Colombo ^[1] ; Hipolito, Ulisses Vilela ^[4] ; Uyemura, Sergio Akira ^[3] ; Tirapelli, Carlos Renato ^[4] ; de Oliveira, Ana Maria ^[2]

Affiliation

^[1] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Pharmacol Lab, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharm Sci Ribeirao Preto, Dept Phys & Chem, Lab Vasc Injury, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Sch Pharm Sci Ribeirao Preto, Dept Clin Toxicol & Bromatol Anal, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Sch Nursing Ribeirao Preto, Pharmacol Lab, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: European Journal of Pharmacology; v. 781, p. 1-9, JUN 15 2016.
• Web of Science Citations: 1

Abstract

Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/I to 1.0 mu mol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5 mu mol/l) and VAS2870 (Nox-4 inhibitor, 5 mu mol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 12/09019-3 - Consequences of dyslipidemia on the ACE - Ang II - AT1 and ACE2 - Ang-(1-7) - mas axes from the angiotensinergic system in aorta from young and adult LDLr knockout mice
• Grantee: Ana Maria de Oliveira
• Support Opportunities: Regular Research Grants