Angiotensin II induces cardiac hypertrophy via oxidative stress but not the antioxidant enzyme system in experimental renovascular hypertension

POLIZIO, ARIEL H.; BALESTRASSE, KARINA B.; YANNARELLI, GUSTAVO G.; NORIEGA, GUILLERMO O.; GORZALCZANY, SUSANA; TAIRA, CARLOS; TOMARO, MARÍA L.

Miami, Florida, USA

Congreso; The Inter-American Society of Hypertension; 2007

The Inter-American Society of Hypertension

Background: Angiotensin II (Ang II) participates in the development of vascular hypertrophy and hypertension. Several studies have demonstrated that reactive oxygen species (ROS) and changes in the activity of antioxidant enzymes are involved in many  vascular responses to Ang II. Objetives: The aim of this study was to establish whether Ang II could modify the activities of antioxidant enzymes in a renovascular model of cardiac hypertrophy, thorough direct action (via AT1 receptor) or indirect action, such as the arterial pressure. On the other hand, it has been determined the levels of oxidative stress markers in rats with abdominal aorta coarctation treated with losartan, an Ang II type 1 receptor antagonist, in an attempt to establish whether the cardiac hypertrophy in rats with aorta coarctation was associated with oxidative stress generated through the activation of the selective AT1 receptors. Methods: Male Wistar rats (250 g) were anaesthetized with ether and submitted to sham operation (Sham) or complete ligation of the abdominal aorta between the right and left renal arteries (Coa). Two groups of Coa and Sham rats (n=7) received losartan (Los), which is a specific antagonist of the angiotensin AT1 receptors, (10 mg/kg/day) or minoxidil (Minoxi) (120mg/ml), a direct acting vasodilator drug, in the drinking water for 7 days.  Four groups, namely Coa-Los, Coa-Minoxi, Sham-Los and Sham-minoxi, were respectively obtained. Control animals were Coa or Sham rats. Results: Oxidative stress production in coarcted rats was confirmed by increased levels in lipid peroxidation and H2O2 content as well as an enhancement of protein expression of p22phox and p47phox NAD(P)H oxidase subunits. Administration of Los, but not Minoxi, totally prevented these effects and the cardiac hypertrophy developed in this model. However, changes in the activities of the antioxidant enzymes catalase and glutathione peroxidase as well as heme oxygenase-1, the rate limiting enzyme in heme catabolism that leads to the formation of antioxidant species, were also prevented in hypertensive animals by minoxidil and losartan treatment. Conclusion: These results let us conclude that, in coarcted animals, the oxidative stress induction and cardiac hypertrophy highly dependents on Ang II, and therefore they are reverted by Los administration. Taken into account the fact that antioxidant enzymes activities reach similar values to normotensive groups when the hypertensive animals received Los or Minoxi, we are able to conclude that arterial pressure regulates antioxidant activities. Findings here reported strongly indicate that Ang II type 1 receptor antagonists administration in renovascular hypertension therapeutic is highly advisable because it may prevent ROS production by NADPH oxidase and therefore, cardiac hypertrophy.