Long-term alpha(1)-adrenergic blockade attenuates diet-induced dyslipidemia and hyperinsulinemia in the rat

This study evaluated the ability of alpha(1)-adrenergic blockade to interfe re with the development of diet-induced hyperlipidemia and deterioration of insulin action. Diets having extremely divergent effects on glucose and li pid metabolism were contrasted. Rats were fed for 4 weeks either a nonpurif ied diet (chow) or a hyperlipidemic (HL) purified diet containing 40% energ y as sucrose, 40% as fat, and 20% as casein. Half of each dietary cohort wa s given the alpha(1)-adrenergic antagonist prazosin (3 mg/kg/day in the foo d). Blood was collected in the fasted state (10 h after food removal) and 2 h after the intake of a meal. In the fasted state, plasma triacylglycerols (TGs) were higher in rats fed the HL diet than in those given chow and wer e not affected by long-term treatment with prazosin. Postprandially, plasma TG increased twofold in the chow-fed group, with or without long-term praz osin. In contrast, prazosin reduced by more than half the eightfold increas e in TG that followed intake of the high-fat meal (Diet x Blocker interacti on; p < 0.002) in the HL cohort. The HL-fed animals also displayed fasting hypercholesterolemia (+30%; p < 0.0001), which was prevented by longterm tr eatment with prazosin. Likewise, the 50% increase in plasma cholesterol tha t followed meal ingestion only in the HL cohort was blunted by the alpha(1) -blocker (Diet x Blocker interaction; p < 0.001). Long-term prazosin also a bolished fasting hyperinsulinemia in the HL cohort, whereas it did not alte r fasting insulin in chow-fed animals (Diet x Blocker interaction; p < 0.00 5). Measurement of postprandial lipoprotein lipase activity in several tiss ues did not suggest the involvement of changes in the absolute availability of the enzyme as a determinant of the hypotriacylglycerolemic action of th e alpha(1)-blocker. Thus long-term alpha(1)-adrenergic blockade, with minim al effects in rats fed a hypolipidemic diet, strongly attenuates several of the fasting and postprandial alterations in plasma variables of lipid and glucose metabolism induced by an extremely lipogenic diet.