EFFECT OF ESTRADIOL-17-BETA ON PRESSER RESPONSES OF RAT MESENTERIC BED TO NOREPINEPHRINE, K-46619(, AND U)

We reinvestigated the effect of estradiol 17 beta on the responses of adrenergic and nonadrenergic vasoconstrictors characterized it in term s of steroid specificity, time course, and the role of classic estroge n receptors. We evaluated the effect of estradiol 17 beta on the press or responses of isolated perfused rat mesenteric vascular bed (McGrego r's preparation). Estradiol 17 beta (7-700 nM) significantly increased the presser response to bolus applications of norepinephrine (NE) (p < 0.05). However, estradiol 17 beta did not significantly increase the responses to endogenous NE release induced by electrical field stimul ation. Other steroids, testosterone, and the 17 alpha isomer of estrad iol (7 and 700 nM) were ineffective. Estradiol 17 beta (700 nM) also s ignificantly increased the maximum presser response of rat mesenteric preparation to both the prostaglandin endoperoxide analogue U-46619 an d to K+. The potentiation by estradiol 17 beta of mesenteric vasoconst riction elicited by NE, K+, and U-46619 was rapid (2-8 min), suggestin g that a nuclear receptor may not be involved. This notion received fu rther support in that significant potentiation of the NE-induced press er response was also observed with estradiol 17 beta conjugated to alb umin (700 nM), but not when electrical field stimulation was used. The conjugate increased the effect of all NE concentrations. Its effect w as also more consistent (p < 0.01) than that elicited by free estradio l 17 beta. The dose-response curve was shifted to the left, and the ma ximum effect was increased. These data suggest that estradiol 17 beta may possess rapid nongenomic actions unrelated to nuclear receptor bin ding and gene transcription.