Increased vascular catecholamine sensitivity and alpha-adrenergic receptor affinity in female and estrogen-treated male rats.

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Abstract
Female sex hormones, in particular estrogens, may increase vascular sensitivity to catecholamines [and may play a role in diseases characterized by abnormal vascular tone]. Segments of small mesenteric arteries (190-290 .mu.m in inside diameter) from male rats treated with 17.beta.-estradiol (10 .mu.g/100 g body weight/day for 5-7 days) in vitro exhibited a 3.2-fold leftward shift in the contractile dose-response curve for norepinephrine, the concentration resulting in half maximal contraction decreasing from a control value of 8.4 .times. 10-7 to 2.6 .times. 10-7 M. The molecular mechanisms which account for this increase in vascular smooth muscle catecholamine sensitivity are unknown. To evaluate directly the possibility that the effects of female sex hormones on the vascular sensitivity to catecholamines are mediated through changes in the .alpha.-adrenergic receptor, radioligand-binding studies using the .alpha.-1 subtype-selective ligand [3H]-WB-4101 were performed on homogenates of mesenteric arteries in control and estrogen-treated male rats, and in control and oophorectomized female rats. Following estrogen treatment (250 .mu.g/100 g body wt), receptor affinity in male rats was increased 1.9-fold for the antagonist [3H]-WB-4101, and receptor density decreased slightly, from 102 .+-. 4 to 85 .+-. 5 fmol/mg protein. Estradiol at doses of 10 and 250 .mu.g/100 g body wt increased receptor affinity for the agonist (-)-epinephrine 2.8- and 5.7-fold, respectively. The lower dose of estradiol also increased receptor affinity for (-)-norepinephrine 4-fold. In female rats, the affinities for [3H]-WB-4101 and (-)-epinephrine were 1.6- and 3.5-fold higher, respectively, than in age-matched males, with no difference in receptor density between the sexes. Following oophorectomy, the affinity for (-)-epinephrine in females was the same as in males. Testosterone treatment did not affect the density or affinity of receptors in females. Estrogens apparently increase the affinity of .alpha.-adrenergic receptors in blood vessels, and the estrogen-induced increase in vascular sensitivity to catecholamine-induced contraction may be mediated, at least in part, by these affinity changes.