Abstract 4892: Olmesartan Potentiates the Vasorelaxation and Anti-hypertensive Effect of Angiotensin(1–7)
It has been described that Olmesartan increases plasma angiotensin-(1–7) [Ang-(1–7)] through increase in ACE2 expression. Here we evaluated the effect of acute treatment with Olmesartan on the anti-hypertensive and vasorelaxing effects of Ang-(1–7). Vascular activity of Ang-(1–7) was evaluated in intact aorta rings of Wistar rats, pre-contracted with phenylephrine (10−7 M). Olmesartan or Losartan were added to the bath at a concentration of 10−7 M, 30 minutes before adding phenylephrine and performing a dose-response curve of Ang-(1–7) (10−10 to 10−6 M). To evaluate the acute effect of Olmesartan on the anti-hypertensive action of Ang-(1–7), experiments were performed in male SHR (14 –16 week-old). Twenty-four hours before the experiments, catheters were implanted into the abdominal aorta for arterial pressure and heart rate (HR) measurements and the femoral vein for intravenous infusions. Different doses of Ang-(1–7) (0.003, 0.03, 0.3 and 3nmol/Kg/min) or saline were infused (30 minutes each), before and after one hour administration of Olmesartan or Losartan (1mg/Kg) by gavage. Acute treatment with Olmesartan augmented the vasodilator effect of Ang-(1–7) in endothelium-intact aortic rings (Emax: 28.28 ± 2.94 vs 14.94 ± 1.37% in vehicle-treated rings). The same treatment with Losartan did not change the Ang-(1–7)-induced vasorelaxation (Emax: 11.08 ± 0.98). Acute infusion of Ang-(1–7) produced a dose-dependent decrease in MAP in conscious SHR. The maximum change during infusion was observed at the highest dose (3 nmol/Kg/min, Δ: −16.6 ± 3.8 mmHg). The anti-hypertensive effect of Ang-(1–7) was markedly enhanced after Olmesartan administration (maximum change: −35.4 ± 5.4 mmHg, at the dose of 3nmol/Kg/min). Losartan treatment produced only a slight increase in the Ang-(1–7) anti-hypertensive effect (Δ: −9.9 ± 6.3 mmHg). Vehicle administration did not change the anti-hypertensive effect of Ang-(1–7). At the doses used, acute administration of both AT1 blockers alone did not change blood pressure. These data show that Olmesartan but not Losartan potentiated the vasorelaxation and anti-hypertensive effects of Ang-(1–7). The absence of effect of the other AT1 blocker Losartan, suggest that this is not a class effect.