European Journal of Clinical Pharmacology

, Volume 43, Issue 2, pp 149–155 | Cite as

The direct effects of diethylstilboestrol and nifedipine on the contractile responses of isolated human and rat detrusor muscles

  • R. A. Elliott
  • C. M. Castleden
  • A. Miodrag
  • P. Kirwan


We have studied the direct effect of 2 µmol·l−1 diethylstilboestrol on isolated rat and human detrusor muscles. Diethylstilboestrol significantly reduced the amplitude of the contractile response of rat detrusor muscle to stimulation with acetylcholine, carbachol, electrical field stimulation, and 5-hydroxytryptamine. In isolated human bladder it also significantly reduced contractions stimulated with acetylcholine, carbachol, and electrical field stimulation. In depolarized rat detrusor muscle stimulated with different concentrations of calcium ions, the contractile responses were significantly reduced by the addition of diethylstilboestrol. Diethylstilboestrol also significantly reduced the amplitude of contractile response to potassium chloride. The inhibitory action of diethylstilboestrol was enhanced by the reduction of extracellular calcium ions, the maximum contractile response to acetylcholine, carbachol, and electrical field stimulation being reduced by a further 32%, 23%, and 45% respectively. Diethylstilboestrol did not have a significant effect on carbachol-induced contractions in depolarized rat detrusor muscle suspended in a calcium-free environment. Diethylstilboestrol was effective in blocking rat and human detrusor muscle contraction. The likely mechanism is a reduction of the influx of calcium ions into the cell during contraction rather than an effect on intracellular calcium release. These results give support for treating incontinent patients with drugs that block calcium ion uptake, and may suggest a further beneficial effect of oestrogen therapy in postmenopausal women.

Key words

Oestrogen Nifedipine Muscle contraction bladder acetylcholine carbachol 5-hydroxytryptamine 


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  1. 1.
    McGrother CW, Castleden CM, Duffin HM and Clarke M (1986) Provision of services for incontinent elderly people at home. J Epid Com Health 40: 134–138Google Scholar
  2. 2.
    Castleden CM, Duffin HM and Asher MJ (1981) Clinical and urodynamic studies in 100 elderly incontinent patients. Br Med J 282: 1103–1105Google Scholar
  3. 3.
    Battcock TM and Castleden CM (1990) Pharmacological treatment of urinary incontinence. Br Med Bull 46: 147–155PubMedGoogle Scholar
  4. 4.
    Molander U, Milsomn I, Ekelund P and Mellstrom D (1990) An epidemiological study of urinary incontinence and related urological symptoms in women. Maturitas 12: 51–60PubMedGoogle Scholar
  5. 5.
    Miodrag A, Castleden CM and Vallance TR (1989) Sex hormones and the female urinary tract. Drugs 36: 491–504Google Scholar
  6. 6.
    Shapiro E (1986) Effect of oestrogens on the weight and muscarinic receptor density of the rabbit bladder and urethra. J Urol 135: 1084–1087PubMedGoogle Scholar
  7. 7.
    Batra S and Andersson KE (1989) Oestrogen-induced changes in muscarinic receptor density and contractile responses in the female rabbit urinary bladder. Acta Physiol Scand 137: 135–141PubMedGoogle Scholar
  8. 8.
    Iosif CS, Batra S, Anders EK and Birger A (1981) Oestrogen receptors in the human female lower urinary tract. Am J Obstet Gynecol 141: 817–820PubMedGoogle Scholar
  9. 9.
    Ingelman-Sundberg A, Rosen J, Gustafsson A and Carlstrom K (1981) Cytosol estrogen receptors in the urogenital tissues in stress incontinent women. Gynaecol Scand 60: 585–586Google Scholar
  10. 10.
    Zar MA, Iravani MM and Luheshi GN (1990) Effect of nifedipine on the contractile response of the isolated rat bladder. J Urol 143: 835–839PubMedGoogle Scholar
  11. 11.
    Maggi CA, Patacchini SGR, Turini D, Barbanti G, Giachetti A and Meli A (1989) Multiple sources of calcium for contraction of the human urinary bladder muscle. Br J Pharmacol 98: 1021–1031PubMedGoogle Scholar
  12. 12.
    Batra S and Bengtsson B (1978) Effects of diethylstilboestrol and ovarian steroids on the contractile responses and calcium movements in rat uterine smooth muscle. J Physiol 276: 329–342PubMedGoogle Scholar
  13. 13.
    Brading AF and Williams JH (1990) Contractile responses of smooth muscle strips from rat and guinea-pig urinary bladder to transmural stimulation: Effects of atropine or alpha, betamethylene ATP. Br J Pharmacol 99: 493–498PubMedGoogle Scholar
  14. 14.
    Sibley GNA (1985) A comparison of spontaneous and nervemediated activity in bladder muscle from man, pig and rabbit. J Physiol 354: 431–443Google Scholar
  15. 15.
    Kinder RB and Mundy AR (1985) Atropine blockade of nervemediated stimulation of the human detrusor. Br J Urol 57: 418–421PubMedGoogle Scholar
  16. 16.
    Chen HI (1990) Evidence for the presynaptic action of 5-hydroxytryptamine and the involvement of purinergic innervation in the rabbit lower urinray tract. Br J Pharmacol 101: 212–216PubMedGoogle Scholar
  17. 17.
    Mostwin JL (1985) Receptor operated intracellular calcium stores in the smooth muscle of the guinea pig bladder. J Urol 133: 900–902PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • R. A. Elliott
    • 1
  • C. M. Castleden
    • 1
  • A. Miodrag
    • 1
  • P. Kirwan
    • 1
  1. 1.University Departments of Medicine for the Elderly and GynaecologyLeicester General HospitalLeicesterUK

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