Acute effects of celiprolol on muscle blood flow and insulin sensitivity: studies using [15O]-water, [18F]-fluorodeoxyglucose and positron emission tomography.
OBJECTIVE
Recently the role of peripheral vasoconstriction in the aetiology of insulin resistance has been proposed. Celiprolol is a beta 1-selective adrenoceptor antagonist with partial agonist activity at the beta 2-receptor as well as vasodilator properties. The acute effects 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 [15O]-labelled water and positron emission tomography (PET) during euglycaemic hyperinsulinaemia (serum insulin approximately 65 mU.1(-1)) after an overnight fast. Thereafter, skeletal and heart muscle glucose uptake were determined using [18F]-2-deoxy-D-glucose.


RESULTS
Celiprolol increased muscle blood flow by 74%, from 3.4 to 5.9 ml.min-1.100 g-1 muscle in the basal state. It decreased peripheral resistance by 40%, from 32.0 to 19.2 mmHg.ml-1.min-1.100 g-1. Celiprolol significantly decreased diastolic blood pressure from 82 to 73 mmHg and increased heart rate from 61 to 68 beats.min-1, which suggests sympathetic activation. Insulin-stimulated glucose uptake was reduced by 46% in the whole body, from 39 to 21 mumol.kg-1.min-1 and by 59% in the femoral muscles, from 99 to 41 mumol.kg-1.min-1, with celiprolol as compared to saline. The effect on heart glucose uptake did not statistically differ between the treatments.


CONCLUSIONS
Celiprolol given intravenously increased muscle blood flow and decreased peripheral resistance at rest. It also acutely increased heart rate probably via sympathetic activation, and decreased insulin sensitivity in the muscles of healthy male volunteers. The enhanced muscle perfusion when celiprolol is given intravenously does not explain the improved insulin sensitivity seen in the long-term oral use in dyslipidaemic hypertensive patients.
Malminiemi
K
K
Tampere University Hospital, Finland.
Laine
H
H
Knuuti
M J
MJ
Ruotsalainen
U
U
Oikonen
V
V
Haaparanta
M
M
Nuutila
P
P
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D017272:Celiprolol / Q000494:pharmacology*; D018592:Cross-Over Studies; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000378:metabolism; D004311:Double-Blind Method; D004341:Drug Evaluation; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D010104:Oxygen Radioisotopes; D012039:Regional Blood Flow / Q000187:drug effects; D014055:Tomography, Emission-Computed; D014665:Vasodilator Agents / Q000494:pharmacology*; D014867:Water
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D005462:Fluorine Radioisotopes; D010104:Oxygen Radioisotopes; D014665:Vasodilator Agents; D014867:Water; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D017272:Celiprolol