Downregulation by estrogen of nitric oxide synthase activity in the female rabbit lower urinary tract

Because female urinary tract tissues are considered to be targets for estrogen, and because nitric oxide (NO) is known to participate in the nerve-induced relaxation in the lower urinary tract, the effect of estrogen on nitric oxide synthase (NOS) in the upper and lower urinary tracts was examined.

Ovariectomized rabbits were treated with polyestradiol phosphate, and NOS in both cytosolic and particulate fractions from kidney, urinary pelvis, ureter, urinary bladder, trigonum, and urethra was characterized. NOS activity was measured by the formation of [14C]-L-citrulline from [14C]-L-arginine.

NOS was considerably higher in cytosolic than in particulate fractions from all urinary tracts, and activity in both fractions was highly calcium dependent. NOS activity was much lower (fourfold to eightfold) in the kidney and pelvis than in the ureter. Estrogen treatment caused no change in NOS in either fraction from upper urinary tract tissues. In the lower urinary tract, NOS was slightly higher in the bladder and trigonum than in the urethra, and activities were comparable to NOS in the ureter. In contrast to the upper urinary tract, estrogen treatment led to a significant reduction of cytosolic NOS in the bladder, trigonum, and urethra. Estrogen, however, caused no significant change in the particulate NOS.

Downregulation by estrogen in cytosolic NOS in the tissue of the lower urinary tract is consistent with the presence of estrogen receptors and suggests a physiologic significance.