Increased alpha1-adrenergic activity in the rat bladder by depletion of ovarian hormones.
OBJECTIVE
It is possible that postmenopausal loss of ovarian hormones leads to sensitization and/or over expression of alpha1-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 alpha1-adrenergic receptors.


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 alpha1-adrenergic agonist phenylephrine, the alpha1-adrenergic antagonist prazosin, the specific alpha1A antagonist 5-methylurapidil or dimethyl sulfoxide (Sigma) 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 alpha1-adrenergic activity.
Dmitrieva
Natalia
N
Program in Neuroscience, Florida State University, Tallahassee, Florida 32306-1270, USA. dmitrieva@psy.fsu.edu
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D009119:Muscle Contraction / Q000187:drug effects; D010052:Ovariectomy; D011224:Prazosin / Q000494:pharmacology*; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D012680:Sensitivity and Specificity; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*; D014554:Urination / Q000187:drug effects / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D011224:Prazosin