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Reversal of sex-related differences in incidence of vascular diseases in Type II diabetics suggests that high circulating insulin may reverse normal differences in vascular actions of sex steroids. We have found that a high concentration of insulin can reverse small inhibitory actions of low estradiol on adrenergic tone in isolated arterial rings. Thus, we measured effects of high insulin on actions of dihydrotestosterone on adrenergic tone and specificity of these effects with respect to time of exposure to the steroid and its concentration. In the first of two studies, tail arterial rings from 16 male rats were incubated for 2 h with either dihydrotestosterone (0.0012 mumol/ L), insulin (0.5 mU/mL), dihydrotestosterone plus insulin, or vehicles. Rings were then contracted with norepinephrine administered cumulatively from 10(-9) to 10(-4) mol/L. Contractile responses to norepinephrine from 10(-7) to 10(-4) mol/L were increased by dihydrotestosterone in the absence (P &lt; .05) but not in the presence of insulin. Also, norepinephrine's EC50 was reduced by dihydrotestosterone in the absence (P &lt; .05) but not in the presence of insulin. In a second study (with rings from 12 more rats), the same low level of dihydrotestosterone failed to affect norepinephrine contractions acutely (that is, within 6 min), whereas much higher levels (12 and 120 mumol/L) rapidly inhibited the same contractions, independent of 2-h preincubation with insulin. Thus, prolonged exposure to a low physiological level of dihydrotestosterone enhances adrenergic tone, whereas acute exposure to high levels inhibits it. In addition, a high level of insulin specifically blunts the delayed enhancing effect of the low dihydrotestosterone. These results suggest possible mechanisms underlying sex-related differences in arterial vascular tone and the potential impact of hyperinsulinemia on such differences.

Interactive effects of insulin with dihydrotestosterone on adrenergic tone in isolated rat tail arterial rings