Vasoprotective effects of neurocompensatory response to balloon injury during diabetes involve the improvement of Mas signaling by TGF beta(1) activation

Author(s)

Pernomian, Larissa ^[1] ; Gomes, Mayara S. ^[1] ; Pernomian, Laena ^[2] ; Moreira, Rafael P. ^[1] ; Correa, Fernando M. A. ^[2] ; de Oliveira, Ana M. ^[1]

Affiliation

^[1] Univ Sao Paulo, FCFRP, Dept Chem & Phys, Lab Vasc Injury, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, FMRP, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: VASCULAR PHARMACOLOGY; v. 64, p. 36-48, JAN 2015.
• Web of Science Citations: 5

Abstract

Balloon injury in diabetic rats triggers a sensory neurocompensatory response that restores the blood flow in contralateral carotid. These vasoprotective effects result from H2O2-mediated relaxation that counteracts AT(1)-dependent contractile hyperreactivity. The most important mechanism from the renin-angiotensin-system in counteracting AT(1)-mediated effects is that one is mediated by Mas receptors. Thus, we hypothesized that the vasoprotective effects of balloon neurocompensation in diabetic rats could result from the improvement of Mas signaling by H2O2-mediated sensory mechanisms. NK1 receptors are sensory components whose activation could lead to H2O2 generation upon TGF beta(1) release and ALK5-mediated Nox4 upregulation. Based on this, we aimed to investigate: (1) the role of the TGF beta(1)/ALK5-Nox4-H2O2 pathway on modulating Mas signaling in diabetic rat contralateral carotid; and (2) the contribution of Mas signaling in the control of local blood flow. Our results showed that balloon neurocompensation restored diabetic rat contralateral carotid flow by improving Mas signaling through NK1-mediated TGF beta(1) release. TGF beta(1)/ALK5 activation enhanced Nox4 expression and Nox4-driven generation of H2O2. In turn, H2O2 enhanced the local Mas-mediated relaxation. Since restenosis impairs diabetic rat ipsilateral carotid flow, the restoration of diabetic rat contralateral carotid flow may prevent further damages in cerebral irrigation by carotid pathways after angioplasty during diabetes. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 14/17740-0 - Planning, development and pharmacological evaluation of new aryl hydrocarbon receptors (AhR) antagonists that are candidates for atheroprotective drugs
• Grantee: Larissa Pernomian
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/01005-0 - Influence of oxidative stress on the response to angiotensin II in contralateral carotid of diabetic rat after balloon-catheter injury
• Grantee: Larissa Pernomian
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/11205-7 - Modulation played by C-type natriuretic peptide (CNP) on the contractile response induced by phenylephrine on thoracic aorta and mesenteric resistance arteries isolated from rats submitted to septic shock
• Grantee: Laena Pernomian
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/00640-7 - Study of the consequences of the inflammatory process induced by AT1 receptors during atherosclerosis on the ACE2 - angiotensin-(1-7) - Mas axis in mouse aorta and the involvement of Mas receptors in the vaso- and atheroprotective effects of losartan
• Grantee: Larissa Pernomian
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC