Left Ventricular Hypertrophy Inhibition, Normalization of the Contractile Response and Oxidative Stress in Experimental Hypertension

Introduction and objectives: Left ventricular hypertrophy secondary to hypertension has been perceived as a protective mechanism toreduce wall stress and prevent heart failure. However, its presence is paradoxically associated with increased cardiovascular morbidity andmortality. The aim of this study was to evaluate whether chronic antihypertensive treatment inhibits the development of left ventricularhypertrophy and normalize the impaired cardiac beta-adrenergic response, and its possible association with changes in myocardial oxidativemetabolism.Methods: Spontaneously hypertensive male rats (SHR, 2 months old) were divided into groups (ngroup = 18) according to (mg/kg, p.o):losartan 30 (L), hydralazine-11 (H), rosuvastatin 10 (R), carvedilol 20 (C), and water (control treatment). The control hypertension groupconsisted of 18 normotensive rats (Wistar-Kyoto, WKY). Systolic blood pressure (SBP) (plethysmography in awake animals) and bodyweight (BW) were measured periodically. The animals were sacrificed at 16 months and 50% of the hearts were mounted in a Langendorffsystem to measure contractility before and after beta-adrenergic stimulation [isoproterenol (Iso): 10-9 M, 10-7 M, and 10-5 M]. In theremaining hearts left ventricular weight (LVW) was measured and normalized by BW. Immunohistochemical expression of thioredoxin 1(Trx-1), peroxyredoxin 2 (Prx-2) and glutaredoxin 3 (Grx-3) (antioxidant indicators) was quantified.Results: Body weight was similar in all groups. Systolic blood pressure (mm Hg) was 154 ± 3 (L), 137 ± 1 (H), 190 ± 3 (R)**, 206 ± 3(SHR)*, 183 ± 1 (C)**, and 141 ± 1 (WKY) (* p < 0.05 vs. L, H, WKY, ** p < 0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR andR (p < 0.05) compared with L, H, C and WKY. In C, there was no correlation between hypertension and left ventricular hypertrophy. SHR,R and C evidenced baseline contractile depression vs. L, H and WKY. The response to 10-5 M Iso was similar in WKY and L, and reducedin C, H, R and SHR. The expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (average increase: 1.5-2 times; p < 0.01 vs. SHRand WKY).Conclusions: Treatment with losartan, hydralazine, and carvedilol prevented the development of left ventricular hypertrophy. Losartannormalized the response to isoproterenol in SHR. Additional factors might participate in the development of left ventricular hypertrophywith impaired inotropic response to beta-adrenergic stimulation in hypertension. The increased expression of thioredoxins as a result ofantihypertensive treatment suggests an additional benefit, increasing the antioxidant response against oxidative stress in hypertensi