Objective: To investigate the effects of angiotensin receptor blocker (ARB) on triglyceride (TG) medoxomil metabolism and mechanism thereof.
Methods: Zucker fatty (ZF) rats and Zucker lean (ZL) rats were fed with water containing 0.01% olmesartan , a highly specific ARB for 4 weeks. Frequently sampled intravenous glucose tolerance test was conducted to calculate the area under the glucose (AUCG), insulin sensitivity index (SI), glucose effectiveness (SG), Blood glucose, TC, TG, nonesterified fatty acid (NEFA), and HDL-C were measured with standard assay kit. Triton WR-1339 technique was used to detect the TG secretion rate (TGSR). After TGSR and FS-IVGTT the levers were collected. The total cholesterol (TC) of the liver was detected, and Sudan IV staining was used to detect the triglyceride in the liver. Enzymatic method was used to measure the TG and TC in the liver extract.
Results: The blood pressure of both groups was lowered in both strains to the same extent after olmesartan taking. The SI value of the ZF rats was (0.31 +/- 0.22) microU x ml(-1) x min(-1) x 10(-4) significantly lower than that of the ZL rats (3.54 +/- 0.30) microU x ml(-1) x min(-1) x 10(-4), P < 0.01). Bergman's minimal model showed that the SG value of the ZF rats was (1.35 +/- 0.51) min(-1) x 10(-2), significantly lower than that of the ZL rats (3.40 +/- 0.14 min(-1) x 10(-2), P < 0.01). The plasma glucose levels of the ZF rats was (11.4 +/- 2.6) mmol/L, significantly higher than that of the L rats [(9.2 +/- 0.6) mmol/L, P < 0.01]. Olmesartan treatment substantially elevated both the baseline SI and SG levels of the ZF rats. The TG of the ZF rats was 6 times as high as that of the ZL rats. The plasma NEFA level after olmesartan treatment of the ZF rats was Olmesartan treatment, significantly lower than that before treatment [(2.70 +/- 0.69) mEq/L, P < 0.01], however, the plasma TG level of the ZF rats after the treatment was not significantly different from that before treatment (P > 0.05). The TGSR rate of the ZF rats was almost 6 times that of the ZL rats. Olmesartan treatment lowered the TG overproduction by half (0.56 +/- 0.08) mg x min(-1) x 100 g(-1) BW vs (0.30 +/- 0.07) mg x min(-1) x 100 g(-1) BW, (P < 0.01). The liver TG content of the ZF rats was 10 times that of the ZL rats. Olmesartan treatment lowered the liver TG content from (22.7 +/- 4.2) mg/g to (12.8 +/- 1.7) mg/g (P < 0.01) without affecting the cholesterol content. Pathology showed that the fatty liver developed in the ZF rats was significantly ameliorated by olmesartan treatment. Olmesartan treatment had no significant effect on TG metabolism or insulin sensitivity in the ZL rats.
Conclusion: ARB improves the overproduction and accumulation of TG in the liver associated with insulin resistance, and does so through mechanisms independent of its hypotensive action.