INTERACTIVE EFFECTS OF INSULIN WITH DIHYDROTESTOSTERONE ON ADRENERGICTONE IN ISOLATED RAT TAIL ARTERIAL RINGS

Reversal of sex-related differences in incidence of vascular diseases in Type II diabetics suggests that high circulating insulin may revers e normal differences in vascular actions of sex steroids. We have foun d that a high concentration of insulin can reverse small inhibitory ac tions of low estradiol on adrenergic tone in isolated arterial rings. Thus, we measured effects of high insulin on actions of dihydrotestost erone on adrenergic tone and specificity of these effects with respect to time of exposure to the steroid and its concentration. In the firs t of two studies, tail arterial rings from 16 male rats were incubated for 2 h with either dihydrotestosterone (0.0012 mu mol/L), insulin (0 .5 mU/mL), dihydrotestosterone plus insulin, or vehicles. Rings were t hen 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 < .05) but not in the presence of insulin. Also, norepinephrine's EC(50) was reduced by dihydrotestosterone in the absence (P < .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 affec t norepinephrine contractions acutely (that is, within 6 min), whereas much higher levels (12 and 120 mu mol/L) rapidly inhibited the same c ontractions, independent of 2-h preincubation with insulin. Thus, prol onged exposure to a low physiological level of dihydrotestosterone enh ances adrenergic tone, whereas acute exposure to high levels inhibits it. In addition, a high level of insulin specifically blunts the delay ed enhancing effect of the low dihydrotestosterone. These results sugg est possible mechanisms underlying sex-related differences in arterial vascular tone and the potential impact of hyperinsulinemia on such di fferences.