Insulin-mediated vasorelaxation in pregnancy.
OBJECTIVE
To investigate insulin-mediated vasorelaxation in pregnancy, and the role of nitric oxide in this response.


METHODS
In vitro study of isolated subcutaneous resistance arteries from pregnant and non-pregnant women.


METHODS
Small arteries (mean vessel diameter <300 microm) were isolated from biopsies of subcutaneous fat from 14 pregnant and seven non-pregnant women. Insulin-mediated attenuation of the vasoconstriction response to noradrenaline, before and after nitric oxide synthase inhibition, was studied in isolated arteries using wire myography. Vessel responses to noradrenaline following incubation with insulin were also tested after endothelial denudation. Maximum responses were compared using one-way ANOVA and Bonferroni's post hoc test for multiple comparisons.


RESULTS
In pregnancy, the maximum vasoconstriction produced by noradrenaline was increased (P < 0.01). Insulin significantly reduced this response in pregnant women (P < 0.01), while inhibition of nitric oxide synthase with Nomega-nitro-L-arginine methyl ester (L-NAME) resulted in potentiation (P < 0.05). Following inhibition of nitric oxide synthase with L-NAME, addition of the insulin was still able to produce a significant attenuation in maximum vasoconstriction to noradrenaline in pregnant women (P < 0.01). Furthermore, the absence of functioning endothelium did not abolish the attenuating effect of the insulin on noradrenaline-induced vasoconstriction in pregnant women (P < 0.01).


CONCLUSIONS
The vasodilatory effect of insulin is not diminished in pregnancy, despite the development of insulin resistance. Furthermore, the attenuation of vasoconstrictor tone is via an endothelium-independent mechanism. This suggests that the vascular dysfunction associated with diabetes mellitus does not occur with physiological insulin resistance.
Ang
C
C
Department of Obstetrics and Gynaecology, University of Glasgow, UK.
Hillier
C
C
MacDonald
A
A
Cameron
A
A
Greer
I
I
Lumsden
M A
MA
D000328:Adult; D000704:Analysis of Variance; D001158:Arteries / Q000187:drug effects; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011247:Pregnancy / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D007004:Hypoglycemic Agents; D007328:Insulin; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D009638:Norepinephrine