Objective. Determine the effect of endogenous estrogen versus estrogen replacement therapy (ERT) on bladder blood flow (BBF) and estrogen receptors (ERs). Methods. BBF was determined with radiolabeled microspheres in luteal, follicular, pregnant, oophorectomized (Ovx) sheep, and Ovx sheep with ERT. Estrogen receptors (ERα, ERβ) were quantified using Western blot analysis. Results. Compared to luteal and follicular ewes, BBF was reduced in pregnancy and following oophorectomy. Estrogen replacement therapy in Ovx sheep restored BBF to luteal levels. Estrogen receptor α predominated, whereas ERβ was not detectable. Estrogen receptor-α levels were unaffected by the ovarian cycle and increased in pregnancy, as well as in Ovx sheep with and without chronic ERT. Conclusion. The combination of diminished BBF and elevated ERα levels in both pregnant and Ovx sheep suggests an inverse relationship between BBF and ERα in the bladder. Although chronic ERT in Ovx sheep restored BBF, it did not restore ERα back to luteal levels.
Magness RR, Phernetton TM, Zheng J.Systemic and uterine blood flow distribution during prolonged infusion of 17beta-estradiol. Am J Physiol. 1998;275(3 pt 2):H731-H743.
2.
Magness RR, Rosenfeld CRThe role of steroid hormones in the control of uterine blood flow. In: Rosenfeld CR, ed. The Uterine Circulation. Ithaca, NY: Perinatology Press;1989: 239-271.
3.
Rosenfeld CR , Morriss FH Jr, Battaglia FC, Makowski EL, Meschia G.Effect of estradiol-17beta on blood flow to reproductive and nonreproductive tissues in pregnant ewes. Am J Obstet Gynecol. 1976;124(6):618-629.
4.
Magness RRMaternal cardiovascular and other physiologic responses to the endocrinology of pregnancy. In: Bazer FW, ed. The Endocrinology of Pregnancy. Totowa, NJ: Humana Press Inc;1998:507-539.
5.
Magness RR, Rosenfeld CR, Carr BRProtein kinase C in uterine and systemic arteries during ovarian cycle and pregnancy. Am J Physiol.1991;260(3 pt 1):E464-E470.
6.
Rupnow HL, Phernetton TM, Shaw CE, Modrick ML, Bird IM, Magness RREndothelial vasodilator production by uterine and systemic arteries. VII. Estrogen and progesterone effects on eNOS. Am J Physiol Heart Circ Physiol.2001;280(4):H1699-H1705.
7.
Gibson TC, Phernetton TM, Wiltbank MC, Magness RRDevelopment and use of an ovarian synchronization model to study the effects of endogenous estrogen and nitric oxide on uterine blood flow during ovarian cycles in sheep. Biol Reprod. 2004;70(6):1886-1894.
8.
Magness RR, Phernetton TM, Gibson TC, Chen DBUterine blood flow responses to ICI 182 780 in ovariectomized oestradiol-17beta-treated, intact follicular and pregnant sheep. J Physiol. 2005;565(pt 1):71-83.
9.
Aikawa K., Chichester P., Whitbeck C., Levin RMEffect of nitric oxide synthase inhibition on changes induced by estradiol in bladders from ovariectomized rabbits. Urol Int. 2005;75(2):133-138.
10.
Bekavac I., Kupesic S., Mihaljevic D., Kurjak A.Vascular impedance of uterine, inferior vesicle, and ophthalmic arteries in postmenopausal women receiving hormonal replacement therapy: comparative Doppler study. Croat Med J. 2000;41(3):235-239.
11.
Parekh MH, Chichester P., Lobel RW, Aikawa K., Levin RMEffects of castration on female rabbit bladder physiology and morphology. Urology. 2004;64(5):1048-1051.
12.
Pinggera GM, Feuchtner G., Frauscher F., et al. Effects of local estrogen therapy on recurrent urinary tract infections in young females under oral contraceptives. Eur Urol. 2005;47(2):243-249.
13.
Battaglia C., Salvatori M., Giulini S., Primavera MR, Gallinelli A., Volpe A.Hormonal replacement therapy and urinary problems as evaluated by ultrasound and color Doppler. Ultrasound Obstet Gynecol. 1999;13(6):420-424.
14.
Badger WJ, Whitbeck C., Kogan B., Chichester P., Levin RMThe immediate effect of castration on female rabbit bladder blood flow and tissue oxygenation. Urol Int. 2006;76(3):264-268.
15.
Greenland JE , Hvistendahl JJ, Andersen H., et al. The effect of bladder outlet obstruction on tissue oxygen tension and blood flow in the pig bladder. BJU Int. 2000;85(9):1109-1114.
16.
Ghafar MA, Shabsigh A., Chichester P., et al. Effects of chronic partial outlet obstruction on blood flow and oxygenation of the rat bladder. J Urol. 2002;167(3):1508-1512.
17.
Kroyer K., Bulow J., Nielsen SL, Kromann-Anderson B.Urinary bladder blood flow. I. Comparison of clearance of locally injected 99mtechnetium pertechnate and radioactive microsphere technique in dogs. Urol Res. 1990;18(3):223-226.
18.
Nielsen KK, Nielsen SL, Nordling J., Kromann-Andersen B.Rate of urinary bladder blood flow evaluated by 133Xe washout and radioactive microspheres in pigs. Urol Res. 1991;19(6): 387-391.
19.
Elicevik M. , Horasanli S., Okaygun E., Badur S., Celayir S.Estrogen receptor beta type in the rat urinary bladder. Arch Androl. 2006;52(5):407-410.
20.
Lin AD, Levin R., Kogan B., et al. Estrogen induced functional hypertrophy and increased force generation of the female rabbit bladder. Neurourol Urodyn . 2006;25(5):473-479.
21.
Aikawa K., Sugino T., Matsumoto S., Chichester P., Whitbeck C., Levin RMThe effect of ovariectomy and estradiol on rabbit bladder smooth muscle contraction and morphology. J Urol. 2003;170(2 pt 1):634-637.
22.
Juan YS, Mannikarottu A., Kogan BA, et al. The effect of low-dose estrogen therapy on ovariectomized female rabbit bladder. Urology. 2008;71(6):1209-1213.
23.
Longhurst PA , Kauer J., Leggett RE, Levin RMThe influence of ovariectomy and estradiol replacement on urinary bladder function in rats. J Urol. 1992;148(3):915-919.
24.
Zhu Q., Ritchie J., Marouf N., et al. Role of ovarian hormones in the pathogenesis of impaired detrusor contractility: evidence in ovariectomized rodents. J Urol . 2001;166(3):1136-1141.
25.
Eika B., Salling LN, Christensen LL, Andersen A., Laurberg S., Danielsen CCLong-term observation of the detrusor smooth muscle in rats. Its relationship to ovariectomy and estrogen treatment. Urol Res. 1990;18(6):439-442.
26.
Lin AD, Mannikarottu A., Kogan BA, et al. Estrogen induces angiogenesis of the female rabbit bladder. J Endocrinol. 2006;190(2):241-246.
27.
Palmieri K. , Mannikarottu AS, Chichester P., et al. The effects of cyclical oestrogen on bladder and urethral structure and function. BJU Int. 2007;99(1):171-176.
28.
Siracusano S., Bertolotto M., d'Aloia G., Silvestre G., Stener S.Colour Doppler ultrasonography of female urethral vascularization in normal young volunteers: a preliminary report. BJU Int.2001;88(4):378-381.
29.
Yang JM, Yang SH, Huang WCFunctional correlates of Doppler flow study of the female urethral vasculature . Ultrasound Obstet Gynecol. 2006;28(1):96-102.
30.
Magness RR, Parker CR Jr, Rosenfeld CRSystemic and uterine responses to chronic infusion of estradiol-17 beta. Am J Physiol.1993;265(5 pt 1):E690-E698.
31.
Ford SP, Reynolds LP, Magness RRBlood flow to the uterine and ovarian vascular beds of gilts during the estrous cycle or early pregnancy. Biol Reprod. 1982 ;27(4):878-885.
32.
Byers MJ, Zangl A., Phernetton TM, Lopez G., Chen DB, Magness RREndothelial vasodilator production by ovine uterine and systemic arteries: ovarian steroid and pregnancy control of ERalpha and ERbeta levels. J Physiol. 2005;565(pt 1):85-99.
33.
Gill HS, Monson FC, Wein AJ, Ruggieri MR, Levin RMThe effects of short-term in-vivo ischemia on the contractile function of the rabbit urinary bladder. J Urol. 1988;139(6): 1350-1354.
34.
Mannikarottu AS, Hypolite JA, Zderic SA, Wein AJ, Chacko S., Disanto MERegional alterations in the expression of smooth muscle myosin isoforms in response to partial bladder outlet obstruction . J Urol. 2005;173(1):302-308.
35.
Pagala MK, Tetsoti L., Nagpal D., Wise GJAging effects on contractility of longitudinal and circular detrusor and trigone of rat bladder. J Urol. 2001;166(2):721-727.
36.
Saito M., Ohmura M., Kondo A.Effect of ageing on blood flow to the bladder and bladder function. Urol Int. 1999;62(2): 93-98.
37.
Sanchez-Ortiz RF, Wang Z., Menon C., DiSanto ME, Wein AJ, Chacko S.Estrogen modulates the expression of myosin heavy chain in detrusor smooth muscle. Am J Physiol Cell Physiol . 2001;280(3):C433-C440.
38.
Cardozo L., Lose G., McClish D., Versi E., de Koning Gans H.A systematic review of estrogens for recurrent urinary tract infections: third report of the hormones and urogenital therapy (HUT) committee. Int Urogynecol J Pelvic Floor Dysfunct.2001;12(1):15-20.
39.
Robinson D. , Cardozo LDThe role of estrogens in female lower urinary tract dysfunction. Urology. 2003;62(4 suppl 1): 45-51.
40.
Simunic V., Banovic I., Ciglar S., Jeren L., Pavicic Baldani D., Sprem M.Local estrogen treatment in patients with urogenital symptoms. Int J Gynaecol Obstet.2003;82(2):187-197.
41.
Azadzoi KM, Tarcan T., Kozlowski R., Krane RJ, Siroky MBOveractivity and structural changes in the chronically ischemic bladder. J Urol. 1999;162(5):1768-1778.
42.
Anderson SG, Hackshaw BT, Still JG, Greiss FC Jr.Uterine blood flow and its distribution after chronic estrogen and progesterone administration. Am J Obstet Gynecol.1977;127(2): 138-142.
43.
Levine MG, Miodovnik M., Clark KEUterine vascular effects of estetrol in nonpregnant ewes. Am J Obstet Gynecol. 1984;148(6):735-738.
44.
Anger JT, Saigal CS, Litwin MSThe prevalence of urinary incontinence among community dwelling adult women: results from the National Health and Nutrition Examination Survey. J Urol. 2006;175(2):601-604.
45.
Stanton SL, Kerr-Wilson R., Harris VGThe incidence of urological symptoms in normal pregnancy. Br J Obstet Gynaecol. 1980;87(10):897-900.
46.
Killam AP, Rosenfeld CR, Battaglia FC, Makowski EL, Meschia G.Effect of estrogens on the uterine blood flow of oophorectomized ewes. Am J Obstet Gynecol. 1973;115(8): 1045-1052.
47.
Hsia TY, Shortliffe LMThe effect of pregnancy on rat urinary tract dynamics. J Urol.1995;154(2 pt 2):684-689.
48.
Rodriguez LV , Wang B., Shortliffe LMStructural changes in the bladder walls of pregnant and hormone-treated rats: correlation with bladder dynamics. BJU Int. 2004;94(9):1366-1372.
49.
Iosif S., Ingemarsson I., Ulmsten U.Urodynamic studies in normal pregnancy and in puerperium. Am J Obstet Gynecol. 1980;137(6):696-700.
50.
Muellner S.Physiological bladder changes during pregnancy and the puerperium. J Urol.1939;41(5):691-695.
51.
Greenland JE , Brading AFUrinary bladder blood flow changes during the micturition cycle in a conscious pig model. J Urol. 1996;156(5):1858-1861.
52.
Lieb J., Kogan B., Das AK, Leggett RE, Schroder A., Levin RMThe effect of urine volume and nitric oxide on basal bladder blood flow: response to catheterization and drainage. Neurourol Urodyn. 2001;20(1):115-124.
