LOSARTAN EFFECT ON CARDIAC NITRIC OXIDE SYNTHESIS IN AN EXPERIMENTAL MODEL OF SYNDROME "X"

MARIEL RUTTLER; WALTER MANUCHA; ROBERTO MIATELLO

Mendoza - Argentina

Congreso; XX Reunión Científica Anual; 2002

Sociedad de Biología de Cuyo

We evaluated the effects of chronic treatment wíth an AT1 antago­nist, losartan (L), on cardíac endothelíal nitríc oxíde synthase (eNOS) expressíon and activity from fructose-fcd rats (FFR), a model of syndrome X. Rats wcrc dividcd ín 4 groups: Control (n = 6); FFR (10% fructose in drinking water, n = 6) and FFR+L (20mg/Kg/d, n = 8). After 8 weeks systolíc blood pressure (SBP mmHg), glucose tolerance test (GTT mmol/L/90 min), rclativc heart wcight (RHW: mg. 1OO'g body weíght), eNOS exprcssíon by semiquantitative RT-PCR (eNOS/GADPH ratio) and eNOS activ­ity by conversion of [3H]-argínine in [3H]-citrullin (dpm.mg'.prot.min") in cardiac homogcnates wcrc dctcrmined. Data (mean ± SEM) were processed by ANOVA. Compared lo Control, FFR ín­creascd PAS (114±1 vs 130±1; p<O.OO1), GTT (880±64 vs 1293±31; P < 0.001) and RHW (225±4 vs 239±5; P < 0.001) and decreascd eNOS expression (1.05±0.1 vs 0.63±0.23; P<0.05) and actívity (27.1±2.6 vs 12.3±1.1; P <0.05). Losartan reduced SBP (105±2 P<0.001), (GTT 1102±44; P<0.05), RHW (202±0.7 p<0.05) and partíally restored cardiac eNOS expression (0.86±0.14, P<0.05)) and activity (22.5±0.7; p<0.05). Data suggest that changes ín eNOS expressíon and actívíty could be involved in the pathology mechanísms as well as in the therapeutic action of AT1 receptor antagonists.