title: Metabolic effects of doxazosin and enalapril in hypertriglyceridemic, hypertensive men. Relationship to changes in skeletal muscle blood flow.
abstract: In a previous open study on the metabolic effects of doxazosin in patients with essential hypertension, subgroup analysis indicated that subjects with an accumulation of risk factors for coronary heart disease (high VLDL triglycerides, low HDL cholesterol and high fasting blood glucose) seemed to benefit most from the metabolic actions of doxazosin treatment. Those results formed the basis of this double-blind, parallel-group study undertaken to elucidate the metabolic effects of 6 months of doxazosin and enalapril treatment in patients with both essential hypertension and hypertriglyceridemia. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp method. Hemodynamic evaluation included measurements of office and ambulatory blood pressure and ultrasonic measurements of femoral artery blood flow. Both drugs significantly reduced both office BP and 24-h ambulatory BP. Office systolic BP was significantly better reduced by enalapril. Doxazosin, in contrast to enalapril, significantly increased insulin sensitivity (by 21%, P = .02). It also reduced serum-triglycerides (by 23%, P = .01), VLDL triglycerides (by 30%, P = .008) and VLDL cholesterol (by 24%, P = .02). This lipid-lowering effect of doxazosin was accompanied by an increase in both plasma lipoprotein lipase activity and the elimination rate of an intravenous fat emulsion load. Neither treatment significantly increased femoral artery blood flow. It is speculated that without measurably increasing blood flow in conduit vessels such as the femoral artery, doxazosin, by capillary recruitment, may prolong the transit time for the blood over the muscle bed, which could explain the increased glucose disposal and increased lipoprotein lipase activity.
authors.affiliation: Department of Geriatrics, Samariterhemmets Hospital, Uppsala, Sweden.
authors.forename: P E
authors.initials: PE
authors.lastname: Andersson
authors.forename: H
authors.initials: H
authors.lastname: Lithell
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015992:Body Mass Index; D004311:Double-Blind Method; D017292:Doxazosin / Q000494:pharmacology* / Q000627:therapeutic use; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000150:complications / Q000378:metabolism*; D007333:Insulin Resistance; D007866:Leg / Q000098:blood supply; D008297:Male; D008875:Middle Aged
chemical_list: D000959:Antihypertensive Agents; D004656:Enalapril; D005947:Glucose; D017292:Doxazosin