Alpha-receptor blockade improves muscle perfusion and glucose uptake in heart failure.
OBJECTIVE
Alpha-adrenergic receptor-mediated vasoconstriction might underlie the insulin resistance seen in conditions associated with increased sympathetic tone, like chronic heart failure (CHF). Alpha-adrenergic receptor blockade by phentolamine could improve forearm blood flow (FBF) and forearm glucose uptake (FGU) in CHF patients.


RESULTS
In 8 CHF patients and in 12 healthy volunteers, FBF (plethysmography) and FGU were measured in both forearms during a 150 min hyperinsulinaemic euglycaemic clamp procedure. During the final 30 min of the clamp, phentolamine was infused into one arm (experimental arm) at a dose of 5.0 μg; min(-1) dL(-1) of forearm volume. Insulin infusion (t = 0-120 min) increased FGU in the two groups, without affecting FBF. In the CHF group, α-adrenergic receptor blockade by phentolamine (t = 120-150 min) further increased FGU in the experimental arm from 3.0 ± 0.7 to 5.0 ± 0.9 μmol min(-1) dL(-1) (P = 0.03). Forearm glucose uptake in the contralateral forearm remained unchanged. In the control group, phentolamine infusion did not increase FGU in the experimental forearm. The increase in blood flow in response to phentolamine was similar in both groups (CHF: 2.1 ± 0.3-7.5 ± 1.7 mL min(-1) dL(-1), P < 0.001; controls 1.5 ± 0.2-5.5 ± 0.8 mL min(-1) dL(-1), P < 0.001 for both, CHF vs. control, P = 0.2). Phentolamine did not affect FBF in the control arm in either group.


CONCLUSIONS
Alpha-adrenergic receptor blockade improves FGU in CHF patients. As the increase in FBF is similar in controls and CHF patients, this might be explained by an improved glucose-extraction capacity in CHF patients.
Gomes
Marc E R
ME
Department of Internal Medicine, University Medical Center Nijmegen, Geert Grooteplein Zuid 8, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Mulder
Alexandra
A
Bellersen
Louise
L
Verheugt
Freek W A
FW
Smits
Paul
P
Tack
Cees J
CJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005542:Forearm / Q000098:blood supply; D006321:Heart; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D015425:Myocardial Reperfusion; D010646:Phentolamine / Q000494:pharmacology / Q000627:therapeutic use*; D010991:Plethysmography; D018709:Statistics, Nonparametric; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D010646:Phentolamine