Abstract 502: Salt-Excess Induced Exacerbated Hypertension Prevention by Telmisartan in Spontaneously Hypertensive Rats

Abstract

The effects of angiotensin receptor blocker (AGA), diuretic, a calcium antagonist (CA), and their combination were evaluated on the progression of cardiovascular damage in spontaneously hypertensive rats (SHR) given salt-excess. To this end, 8-week male SHR rats were divided into 7 groups. The control group (C) received regular NaCl (0.6%) diet. All other groups were given 8% NaCl rat chow. In addition, Group 2 (HS) was given placebo, Group 3 (T) the AGA telmisartan (10 mg/kg/day), Group 4 (D) received the chlorothiazide (80 mg/kg/day), Group 5 (T+D) telmisartan plus diuretic, Group 6 (A) was given the CA amlodipine (10 mg/kg/day), and Group 7 (T+A) telmisartan plus amlodipine. All treatments lasted 8 weeks. Compared with controls, mean arterial pressure (MAP), renal blood flow, coronary flow reserve (CFR), minimal coronary vascular resistance, diastolic time constant, and maximal rate of ventricular pressure fall (-dP/dT) were all adversely affected by salt-loading (Table). Increased left ventricular weight (LVWI) with marked cardiac fibrosis was also found with salt overload. Telmisartan normalized all indices except MAP, whereas diuretic and amlodipine only partially restored cardiac function and mass. Combination therapy with telmisartan and either diuretic or amlodipine also normalized all indices including arterial pressure (Table). These data show that: (1) cardiovascular and renal damage induced by salt-excess in SHR were not pressure dependent; and (2) compared with the CA and diuretic, AGA was more effective in this model suggesting that local renin in target organs participated in salt-induced hypertension.