Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Enhanced endothelium-dependent relaxation of rat pulmonary artery following beta-adrenergic overstimulation: Involvement of the NO/cGMP/VASP pathway

Full text
Author(s):
Davel, Ana P. [1] ; Victorio, Jamaira A. [1] ; Delbin, Maria A. [1] ; Fukuda, Livia E. [2] ; Rossoni, Luciana V. [2]
Total Authors: 5
Affiliation:
[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, UNICAMP, BR-13083865 Campinas, SP - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Life Sciences; v. 125, p. 49-56, MAR 15 2015.
Web of Science Citations: 7
Abstract

Aims: The aim of this study was to investigate whether beta-adrenoceptor (beta-AR) overstimulation induced by in vivo treatment with isoproterenol (ISO) alters vascular reactivity and nitric oxide (NO) production and signaling in pulmonary arteries. Main methods: Vehicle or ISO (0.3 mg kg(-1), day(-1)) was administered daily to male Wistar rats. After 7 days, the jugular vein was cannulated to assess right ventricular (RV) systolic pressure (SP) and end diastolic pressure (EDP). The extralobar pulmonary arteries were isolated to evaluate the relaxation responses, protein expression (Western blot), NO production (diaminofluorescein-2 fluorescence), and cyclic guanosine 3',5'-monophosphate (cGMP) levels (enzyme immunoassay kit). Key findings: ISO treatment induced RV hypertrophy; however, no differences in RV-SP and EDP were observed. The pulmonary arteries from the ISO-treated group showed enhanced relaxation to acetylcholine that was abolished by the NO synthase (NOS) inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME); whereas relaxation elicited by sodium nitroprusside, ISO, metaproterenol, mirabegron, or KCI was not affected by ISO treatment. ISO-treated rats displayed enhanced endothelial NOS (eNOS) and vasodilator-stimulated phosphoprotein (VASP) expression in the pulmonary arteries, while phosphodiesterase-5 protein expression decreased. ISO treatment increased NO and cGMP levels and did not induce eNOS uncoupling. Significance: The present data indicate that beta-AR overactivation enhances the endothelium-dependent relaxation of pulmonary arteries. This effect was linked to an increase in eNOS-derived NO production, cGMP formation and VASP content and to a decrease in phosphodiesterase-5 expression. Therefore, elevated NO bioactivity through cGMP/VASP signaling could represent a protective mechanism of beta-AR overactivation on pulmonary circulation. (C) 2015 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 11/15972-2 - INVOLVEMENT OF RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM ACTIVATION ON THE VASCULAR EFFECTS OF BETA-ADRENOCEPTOR HYPERACTIVATION.
Grantee:Jamaira Aparecida Victorio
Support Opportunities: Scholarships in Brazil - Master