Increased αl-adrenergic activity in the rat bladder by depletion of ovarian hormones

Purpose: It is possible that postmenopausal loss of ovarian hormones leads to sensitization and/or over expression of alpha 1-adrenergic receptors. The objective of this study was to determine whether ovariectomy enhances efferent transmission and, hence, increases contractility in the rat bladder by increasing alpha 1-adrenergic receptors. Materials and Methods: This hypothesis was tested in 4 urethane anesthetized groups of female rats, including regularly cycling rats in metestrus and proestrus, and rats 4 months after ovariectomy with and without estradiol replacement, respectively. The bladder was catheterized through the urethra to measure intravesical pressure. The left femoral artery was also catheterized for local delivery of the nonspecific alpha 1-adrenergic agonist phenylephrine, the alpha 1-adrenergic antagonist prazosin, the specific alpha 1A antagonist 5-methylurapidil or dimethyl sulfoxide (Sigma (R)) in saline vehicle. In some rats bladder contractility was assessed by cystometry, followed by treatment with phenylephrine injected via the femoral artery. In other rats the bladder was denervated and a platinum electrode was wrapped around branches of the left pelvic nerve for electrical stimulation. The amplitude of micturition contractions and contractions evoked by phenylephrine or pelvic nerve stimulation was measured. Results: Micturition and phenylephrine evoked bladder contractions were significantly increased in ovariectomized rats without estradiol replacement. Prazosin significantly decreased contractions evoked by pelvic stimulation in a dose dependent manner. This decrease was significantly larger in ovariectomized rats without estradiol replacement compared to that in the other groups. The inhibition of stimulation evoked contractions by 5-methylurapidil was also greater in ovariectomized rats without estradiol replacement than in rats with estradiol replacement. Conclusions: Results suggest that the depletion of ovarian hormones after ovariectomy enhances alpha 1-adrenergic activity.