Chronic ANG II infusion increases plasma triglyceride level by stimulating hepatic triglyceride production in rats

We recently observed that ANG II receptor blocker therapy improved the overproduction of triglyceride (TG) in fructose-fed rats and Zucker fatty rats with insulin resistance, which in turn suggests that ANG II may stimulate TG production. Accordingly, we investigated the effects of ANG II on TG production and the association with insulin resistance in normal rats. Male Wistar rats were continuously infused with ANG II (100 ng.min(-1).kg body wt(-1)) via an osmotic minipump for 14 days. ANG II infusion markedly elevated both the systolic and diastolic blood pressure. The plasma TG level increased twofold, but cholesterol was unchanged. ANG II infusion stimulated the TG secretion rate (TGSR) by twofold and increased the hepatic TG content by 31%. Lipogenesis determined by 2-(3)H]glycerol incorporation into hepatic TG was also significantly increased in ANG II-infused rats. The stimulatory effect of ANG II on TGSR was dose dependent and was not observed until 2 wk after the start of infusion. ANG II infusion significantly reduced insulin sensitivity index (SI) without affecting glucose effectiveness determined by Bergman's minimal model. The plasma TG level was positively correlated with TGSR (r = 0.88, P < 0.001) and inversely with SI (r = -0.80, P < 0.005). These results suggest that chronic ANG II infusion stimulates hepatic TG production, which is partly associated with simultaneous development of insulin resistance. Our results may suggest a new mechanism for the intimate association between hypertension and dyslipidemia.