The effect of 17-alpha-estradiol, a possible endogenous opiate antagonist, on D-ala2-met5-enkephalinamide-induced blood pressure responses in conscious, unrestrained rats.

D-ala2-met5-enkephalinamide (DAME) produced a dose-related increase in the mean arterial blood pressure of conscious, unrestrained rats. Intravenous injection of DAME (0.5, 1, 2, and 4 mg/kg) resulted in mean systemic arterial blood pressures of 138 +/- 2, 146 +/- 5, 141 +/- 4, 156 +/- 5 mmHg, respectively. 17-alpha-estradiol and its derivatives are known to be inactive in target tissues responsive to estrogenic hormones such as 17-beta-estradiol. However, LaBella et al. (1978) found after testing a large number of steroid hormones and their metabolites that only 17-alpha-estradiol significantly inhibited binding of 3H-naloxone, an opiate antagonist, in rat-brain homogenates. The present study was designed to determine whether 17-alpha-estradiol could antagonize the cardiovascular responses elicited by intravenous injections of DAME. Intravenous infusion of 17-alpha-estradiol (1.5 mg/kg) every 2 hours for 24 hours (total infusion time was 2 minutes for each infusion) did not change the mean systemic arterial blood pressure (94 +/- 5 mmHg) compared to the blood pressure prior to infusion of 17-alpha-estradiol (99 +/- 7 mmHg). Intravenous infusion of 17-alpha-estradiol (1.5 mg/kg) 10 minutes prior to DAME (1 mg/kg, i.v.) resulted in a blood pressure of 106 +/- 9 mmHg, which is significantly less than the blood pressure of 146 +/- 5 mmHg seen with DAME (1 mg/kg, i.v.) alone. Intravenous injection of DAME (1 mg/kg) 8 hours after the last infusion of 17-alpha-estradiol produced an increase in mean systemic arterial blood pressure of 136 +/- 8 mmHg. These results indicate that 17-alpha-estradiol may function as an opiate antagonist.