Abstract
Insulin resistance (IR) is a risk factor for cerebrovascular disease. We evaluated the responses to insulin in isolated cerebral arteries from Zucker obese rats (ZO) with IR and lean rats (ZL). Insulin responses were determined in the presence and absence of endothelium, inhibitors of calcium‐activated K+ channels (KCa), NOS and NADPH oxidase (iberiotoxin, L‐NAME and apocynin, respectively). Insulin induced only vasodilation in ZL while a biphasic response with an initial constriction followed by a diminished dilation was observed in ZO (‰ maximal relaxation: 52±10 in ZL vs. 13±8 in ZO, p<0.05). Iberiotoxin abolished vasodilation to insulin in both groups. In ZL, L‐NAME promoted vasoconstriction to insulin while apocynin had no effect. In ZO, insulin induced vasoconstriction was reduced by L‐NAME and apocynin. Endothelial denudation diminished vasodilation to insulin in ZL while ZO were unaffected, suggesting an endothelium independent vasodilation in ZL. Thus, insulin induced vasodilation in cerebral arteries was mediated by endothelium, NO and KCa channels. Insulin caused abnormal vasoconstriction and diminished vasodilation in ZO that may be due to oxidative stress from uncoupled eNOS and NADPH oxidase. Support: NIH grants HL‐030260, HL‐065380, HL‐077731.
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