Introduction: Angiotensin (Ang)-(1–7) may in part counteract the Ang II-induced actions in the cardiovascular systemt through the MAS receptor (MAS). Angiotensin receptor blockers (ARBs) may increase plasma concentration of Ang-(1–7) suggesting that this peptide could be involved in the beneficial effects of these drugs. Hypothesis: Chronic treatment with the ARB olmesartan (OLM) improves vascular remodelling in spontaneously hypertensive rats (SHR) in part through the activation of MAS. Methods: SHR (14 weeks) were treated or not with OLM (10 mg/kg/day, n=3) ± the selective MAS antagonist A-779 (11 pmol/min, n=3), for 14 days. Blood pressure (BP) was measured by tail-cuff method. Mesenteric arteries media-to-lumen ratio (M/L) was evaluated on pressurized preparations. The expression of MAS, eNOS and the NADPH subunit gp91phox in aorta was evaluated by immunoblotting. The reactive oxygen species (ROS) production was evaluated by Dihydroethidium (DHE) staining. Results: BP was reduced in SHR treated with OLM compared to untreated rats (167.3±3.4 mmHg vs 194±4 mmHg, respectively, P<0.05). A-779 treatment had no effect on BP. M/L was reduced in OLM-treated SHR compared to untreated rats (6.07±0.09% vs 8.25±.05%, respectively, –26%, P<0.05). A-779 significantly increased M/L in OLM-treated SHR (+15%, P<0.05). MAS expression was increased by OLM (+40% vs untreated rats, P<0.05), A-779 prevented MAS increase in OLM-treated SHR. eNOS expression was increased two-fold in OLM-treated SHR as compared to untreated rats (p<0.05). A-779 significantly reduced eNOS expression in OLM-treatd SHR (–67%, p<0.05). OLM reduced gp91phox expression in SHR (–63% vs untreated SHR, p<0.05). A-779 significantly increased gp91phox expression in OLM-treated SHR (+24%, p<0.05). OLM reduced ROS production in SHR compared to untreated rats (11.5±0.6 AU vs 16.6±0.45 AU, respectively, p<0.05). A-779 significantly prevented the OLM induced effect on ROS production. Conclusions: OLM improved vascular remodelling, reduced M/L and oxidative stress in SHR in part through the increased expression and activation of MAS, independently by blood pressure reduction.
Role of MAS Receptor Activation on Vascular Remodelling in Presence of Angiotensin II Receptor Blockade in Spontaneously Hypertensive Rats / Savoia, Carmine; Rossi, C; Arrabito, E; Parente, R; Renzi, J; Alonzo, Alessandro; Nicoletti, Carmine; Madaro, Luca; Zezza, L; Sada, L; Bouche', Marina; Volpe, Massimo. - In: CIRCULATION. - ISSN 0009-7322. - ELETTRONICO. - 122:(2010), pp. A16883-A16883. (Intervento presentato al convegno American Heart Association meeting 2010 tenutosi a Chicago, Illinois nel 13 - 17 Nov, 2010).
Role of MAS Receptor Activation on Vascular Remodelling in Presence of Angiotensin II Receptor Blockade in Spontaneously Hypertensive Rats
SAVOIA, Carmine;ALONZO, ALESSANDRO;NICOLETTI, CARMINE;MADARO, LUCA;BOUCHE', Marina;VOLPE, Massimo
2010
Abstract
Introduction: Angiotensin (Ang)-(1–7) may in part counteract the Ang II-induced actions in the cardiovascular systemt through the MAS receptor (MAS). Angiotensin receptor blockers (ARBs) may increase plasma concentration of Ang-(1–7) suggesting that this peptide could be involved in the beneficial effects of these drugs. Hypothesis: Chronic treatment with the ARB olmesartan (OLM) improves vascular remodelling in spontaneously hypertensive rats (SHR) in part through the activation of MAS. Methods: SHR (14 weeks) were treated or not with OLM (10 mg/kg/day, n=3) ± the selective MAS antagonist A-779 (11 pmol/min, n=3), for 14 days. Blood pressure (BP) was measured by tail-cuff method. Mesenteric arteries media-to-lumen ratio (M/L) was evaluated on pressurized preparations. The expression of MAS, eNOS and the NADPH subunit gp91phox in aorta was evaluated by immunoblotting. The reactive oxygen species (ROS) production was evaluated by Dihydroethidium (DHE) staining. Results: BP was reduced in SHR treated with OLM compared to untreated rats (167.3±3.4 mmHg vs 194±4 mmHg, respectively, P<0.05). A-779 treatment had no effect on BP. M/L was reduced in OLM-treated SHR compared to untreated rats (6.07±0.09% vs 8.25±.05%, respectively, –26%, P<0.05). A-779 significantly increased M/L in OLM-treated SHR (+15%, P<0.05). MAS expression was increased by OLM (+40% vs untreated rats, P<0.05), A-779 prevented MAS increase in OLM-treated SHR. eNOS expression was increased two-fold in OLM-treated SHR as compared to untreated rats (p<0.05). A-779 significantly reduced eNOS expression in OLM-treatd SHR (–67%, p<0.05). OLM reduced gp91phox expression in SHR (–63% vs untreated SHR, p<0.05). A-779 significantly increased gp91phox expression in OLM-treated SHR (+24%, p<0.05). OLM reduced ROS production in SHR compared to untreated rats (11.5±0.6 AU vs 16.6±0.45 AU, respectively, p<0.05). A-779 significantly prevented the OLM induced effect on ROS production. Conclusions: OLM improved vascular remodelling, reduced M/L and oxidative stress in SHR in part through the increased expression and activation of MAS, independently by blood pressure reduction.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
