Angiotensin II-dependent vascular alterations in young cardiomyopathic hamsters: role for oxidative stress

Recent studies indicate the presence of vascular alterations in 2-month-old Syrian cardiomyopathic hamsters (SCH). These alterations include enhanced angiotensin-converting enzyme (ACE) activity in the aorta, increased contractile response to angiotensin II and impaired vasorelaxation to acetylcholine in norepinephrine-precontracted aortic rings. The mechanisms leading to these vascular alterations are not known nor has their relationship to the cardiac abnormalities been established. We assessed the status of the cardiovascular system of 2-month-old hamsters first to establish if the observed vascular alterations are secondary to cardiac dysfunction, and second to examine the role of oxidative stress in the etiology of vascular dysfunction. Cardiac function parameters evaluated by echocardiography included stroke volume (SV), left ventricular end-diastolic volume (LVEDV), left ventricular fractional shortening (LVFS), ejection fraction (EF), cardiac output index (COI), heart rate (HR) and left ventricular posterior wall thickness (LVPWT). In addition, heart/body weight (heart/BW) ratios and systolic blood pressure were determined in normal hamsters and SCH. Our results indicated that systolic blood pressure increased 56% in SCH when compared to control animals (P<0.05). The increased blood pressure coexisted with normal COI, SV, LVEDV, LVPWT, LVFS, EF, HR and heart/BW ratios. NAD(P)H oxidase activity increased 77% in SCH compared to control animals (P<0.02). The increased oxidase activity was abolished by pre-treatment of animals with the angiotensin II type 1 receptor blocker losartan (25 mg/kg BW/day) for 10 days. Losartan also abolished the increased blood pressure observed at 2 months of age. The antioxidant N-acetylcysteine (NAC) abrogated the increased blood pressure when administered for 30 days to 1-month-old animals. Altogether, these findings suggest that the angiotensin II-dependent vascular abnormalities present in young cardiomyopathic hamsters are associated with oxidative stress and precede the echocardiographic abnormalities characteristic of heart failure.