A possible link between endothelial dysfunction and insulin resistance in hypertension. A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension.
BACKGROUND
We wanted to investigate whether insulin resistance and time to steady state during isoglycemic clamp were associated with endothelial dysfunction, peripheral vascular remodeling and forearm blood flow (FBF) in patients with longstanding hypertension.


METHODS
In 43 unmedicated, hypertensive patients with electrocardiographic-defined left ventricular hypertrophy we performed a 2-h oral glucose tolerance test and a 3-h isoglycemic hyperinsulinemic clamp with measurements of circulating plasma epinephrine and FBF by plethysmography. Delayed steady state was assessed by measuring the increase in insulin sensitivity from the second to the third hour of clamping. We measured 24-h ambulatory blood pressure, minimal forearm vascular resistance (MFVR) by plethysmography, media:lumen ratio (MLR) and acetylcholine-induced relaxation (AIR) in isolated, subcutaneous resistance arteries by myography.


RESULTS
Insulin sensitivity after 2 and 3 h of clamping was not related to maximal AIR, MLR, MFVR or FBF. The increase in insulin sensitivity in men was negatively correlated to maximal AIR (r = -0.36, p < 0.05), and was independently correlated to relative changes in FBF (beta = 0.46) and in circulating epinephrine (beta = 0.33; adj. R = 0.33, p < 0.001).


CONCLUSIONS
Insulin sensitivity was not correlated to parameters of peripheral vascular remodeling, endothelial function or microvascular rarefaction in patients with longstanding hypertension and left ventricular hypertrophy. However, the action of insulin on peripheral glucose uptake was influenced by endothelial dysfunction (delayed transcapillary insulin transport) and by changes in and/or redistribution of blood flow suggesting a link between vascular function and insulin sensitivity.
Olsen
M H
MH
Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, University of Copenhagen, Denmark. mho@dadlnet.dk
Andersen
U B
UB
Wachtell
K
K
Ibsen
H
H
Dige-Petersen
H
H
D000368:Aged; D001808:Blood Vessels / Q000503:physiopathology; D002196:Capillaries; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005542:Forearm / Q000098:blood supply; D005947:Glucose / Q000493:pharmacokinetics; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000150:complications; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow
D007328:Insulin; D005947:Glucose; D004837:Epinephrine