ACUTE EFFECTS OF CELIPROLOL ON MUSCLE BLOOD-FLOW AND INSULIN SENSITIVITY - STUDIES USING [O-15]-WATER, [F-18] FLUORODEOXYGLUCOSE AND POSITRON EMISSION TOMOGRAPHY

Objective: Recently the role of peripheral vasoconstriction in the aet iology of insulin resistance has been proposed. Celiprolol is a beta(1 )-selective adrenoceptor antagonist with partial agonist activity at t he beta(2)-receptor as well as vasodilator properties. The acute effec ts of celiprolol on skeletal muscle blood flow and insulin sensitivity were measured in this study. Methods: Celiprolol (2 times 0.5 mg.kg(- 1)) or saline was given intravenously to five healthy males in random order. Muscle blood flow was measured in femoral regions using [O-15]- labelled water and positron emission tomography (PET) during euglycaem ic hyperinsulinaemia (serum insulin similar to 65 mU.l(-1)) after an o vernight fast. Thereafter, skeletal and heart muscle glucose uptake we re determined using [F-18]-2-deoxy-D-glucose. Results: Celiprolol incr eased muscle blood flow by 74%, from 3.4 to 5.9 ml.min(-1).100 g(-1) m uscle in the basal state. It decreased peripheral resistance by 40%, f rom 32.0 to 19.2 mmHg.ml(-1).min(-1).100 g(-1). Celiprolol significant ly decreased diastolic blood pressure from 82 to 73 mmHg and increased heart rate from 61 to 68 beats.min(-1), which suggests sympathetic ac tivation. Insulin-stimulated glucose uptake was reduced by 46% in the whole body, from 39 to 21 mu mol.kg(-1).min(-1) and by 59% in the femo ral muscles, from 99 to 41 mu mol.kg(-1).min(-1), with celiprolol as c ompared to saline. The effect on heart glucose uptake did not statisti cally differ between the treatments. Conclusion: Celiprolol given intr avenously increased muscle blood flow and decreased peripheral resista nce at rest. It also acutely increased heart rate probably via sympath etic activation, and decreased insulin sensitivity in the muscles of h ealthy male volunteers. The enhanced muscle perfusion when celiprolol is given intravenously does not explain the improved insulin sensitivi ty seen in the long-term oral use in dyslipidaemic hypertensive patien ts.