The effect of insulin on the vascular reactivity of isolated resistance arteries taken from healthy volunteers.
Impaired reactivity of the resistance vasculature may contribute to the development of diabetic microangiopathy by altering microvascular haemodynamics. This study investigates the acute effects of insulin on the contractility and relaxation properties of isolated human resistance arteries (< 300 microns internal diameter) taken from gluteal subcutaneous fat of 33 (18 male: 15 female) normotensive healthy volunteers (supine blood pressure 115.6 +/- 1.6/70.0 +/- 1.5 mm Hg [mean +/- SEM], with no family history of hypertension or diabetes mellitus. Resistance arteries were mounted in a small vessel myograph to measure isometric tension. Contractile responses to noradrenaline were reduced after incubation in 1 mU/ml of insulin for 20 min (p < 0.01; Group 1). Increasing concentrations of insulin were found to reduce the contractile response to noradrenaline in a dose-dependent manner (Group 2; 0.1 mU/ml by 8% [p < 0.01], 1 mU/ml by 17% [p < 0.02] and 10 mU/ml by 22% [p < 0.01]). Sensitivity to insulin (ED50) only decreased at the highest concentration of insulin. However, acetylcholine-induced relaxation was not altered by insulin (Group 2). Time control studies (Group 3) showed that contractile and relaxation responses over the 4-h study period were unchanged. Furthermore, the length of time the vessels were exposed to insulin did not progressively impair responses (Group 4). These findings suggest that insulin may induce abnormalities in vascular smooth muscle contractility, a factor that may contribute to or exacerbate the abnormal haemodynamics observed in the capillary microcirculation of numerous vascular beds in diabetes.
McNally
P G
PG
Department of Diabetes, University of Leicester, Leicester Royal Infirmary, UK.
Lawrence
I G
IG
Watt
P A
PA
Hillier
C
C
Burden
A C
AC
Thurston
H
H
D000109:Acetylcholine / Q000494:pharmacology; D000273:Adipose Tissue / Q000098:blood supply* / Q000166:cytology; D000704:Analysis of Variance; D001158:Arteries / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001706:Biopsy; D001794:Blood Pressure; D002196:Capillaries / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D012016:Reference Values; D012680:Sensitivity and Specificity; D014655:Vascular Resistance / Q000187:drug effects
D007328:Insulin; D000109:Acetylcholine; D009638:Norepinephrine