4 WEEK ADMINISTRATION OF AN ACE-INHIBITOR AND A CARDIOSELECTIVE BETA-BLOCKER IN HEALTHY-VOLUNTEERS - NO INFLUENCE ON INSULIN SENSITIVITY

In most, but not all, studies antihypertensive treatment with angioten sin converting enzyme inhibitors (ACE inhibitors) improves insulin sen sitivity, whereas beta-blockers decrease insulin sensitivity. However, there was a significant increase in body weight with beta-blockers an d changes in the body potassium homeostasis with ACE inhibitors. In or der to compare the drug specific metabolic effects of an ACE inhibitor and a cardioselective beta-blocker controlling these factors, we meas ured insulin sensitivity in a randomized, double-blind cross-over stud y in 22 healthy; volunteers (age 27 +/- 3 years; BMI 22.0 +/- 1.5 kg m (-2) (mean +/-SD)) during euglycaemic glucose clamps before and after 4 weeks' administration of 5 mg Lisinopril or 5 mg Bisoprolol. Both dr ug phases were separated by 4 weeks of no drug administration. During the insulin sensitivity measurements potassium concentrations were cla mped at basal levels by means of a variable i.v. potassium infusion. B ody weight was monitored at weekly intervals and kept constant within +/- 1 kg of the subjects' baseline weight throughout the entire study period. Insulin sensitivity did not change significantly during either drug administration period. The insulin sensitivity index of the 22 v olunteers after administration of the ACE inhibitor was 7.9 +/- 2.4 mL min(-1) m(2) mu U mL(-1) (basal index 8.3 +/- 1.9 mL min(-1) m(2) mu U-1 mL(-1) and 7.5 +/- 2.1 mL min(-1) m(2) mu U-1 m(-1) after administ ration of the beta-blocker (basal index 8.2 +/- 1.9 mL min(-1) m(2) mu U-1 mL(-1) NS). In order to maintain blood potassium concentrations d uring the glucose clamps at basal levels of 3.9 +/- 0.3 mmol1(-1) a me an of 7.9 +/- 4.2 mval of potassium had to be infused during the low i nsulin step and a mean of 24.1 +/- 9.7 mval during the high insulin st ep. Systolic and diastolic blood pressure were lowered significantly b y Lisinopril (5 +/- 8 mmHg and 7 +/- 9 mmHg) and Bisoprolol (7 +/- 7 m mHg and 4 +/- 8 mmHg; NS between both drugs), respectively. In healthy normotensive subjects administration of Lisinopril or Bisoprolol for 4 weeks does not sensitivity, when appropriate experimental conditions are maintained.