Full text
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| Author(s): |
Jamaira Aparecida Victorio
Total Authors: 1
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| Document type: | Master's Dissertation |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2014-03-02 |
| Examining board members: |
Luciana Venturini Rossoni;
Helena Coutinho Franco de Oliveira
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| Advisor: | Ana Paula Couto Davel |
| Abstract | |
ß-adrenergic (ß¿AR) receptors overstimulation plays an important role in the pathogenesis of cardiovascular diseases concurrent with sympathetic overactivity. It has been suggested to increase plasma levels of angiotensin II and aldosterone. In line with this, angiotensin II/AT1 receptor or mineralocoticoid (MR) receptor antagonism partially prevents the cardiac remodeling induced by ß-AR overstimulation mediated by isoproterenol (ISO) administration. However the implication of angiotensin II or aldosterone on vascular effects provoked by ß¿AR overstimulation is not yet elucidated. So, the aim of the present study was to investigate the AT1 and MR receptor signaling pathway on vascular alterations caused by 7-day ISO treatment on rat aorta, as well as the mechanisms involved. For this, male Wistar rats (3-month-old) were treated with ISO (0.3 mg/kg/day, s.c.) or vehicle (CT) and co-treated or not with AT1 antagonist losartan (LOS; 40 mg/kg/day, v.o.) or MR receptor antagonist spironolactone (ESP; 200 mg/kg/day, v.o.). The ISO treatment resulted in ventricular hypertrophy without hemodynamic alterations, and LOS or ESP co-treatment attenuated the ventricular remodeling of ISO group. ISO aorta showed an increased phenylephrine maximum response associated with a decreased nitric oxide (NO) bioavailability and an increased in superoxide anion; both effects were prevented by ESP co-treatment, but not by LOS. Beneficial effects of ESP on vascular reactivity of aorta from ISO-treated rats were accompanied by an increased HSP90 protein expression, which was reduced in ISO group. Moreover, ESP prevented the increased protein expression of ß-arrestin, Gai, p- Src, ERK1/2 and p-ERK1/2 and osteopontina gene expression in the aorta from ISO group. Plasma corticosterone and aldosterone were not changed between the groups. In conclusion, our results suggest that spironolactone, an MR receptor antagonist prevented the increased phenylephrine contractile response in aorta from ISO-treated rats, associated with increased NO bioavailability and decreased oxidative stress; increased expression of HSP90 and; prevented the increase of ß-arrestin, Gai1,2, p-Src, ERK1/2 and p-ERK1/2 and osteopontin induced by ß-adrenergic overstimulation. These results suggest that the vascular effects induced by ISO in aorta are mediated by a MR activation (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 |