Effects of gender, age and hypertension on β-adrenergic receptor function in rat urinary bladder

被引:0
作者
Elfaridah P. Frazier
Tim Schneider
Martin C. Michel
机构
[1] University of Amsterdam,Department of Pharmacology and Pharmacotherapy
[2] University of Duisburg-Essen,Department of Urology and Medicine
[3] Academisch Medisch Centrum,undefined
[4] Afd. Farmacologie en Farmacotherapie,undefined
来源
Naunyn-Schmiedeberg's Archives of Pharmacology | 2006年 / 373卷
关键词
Bladder; Relaxation; β-adrenoceptor; Gender; Ageing; Hypertension;
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学科分类号
摘要
β-Adrenoceptors mediate urinary bladder relaxation, and gender, age and hypertension have been linked to bladder dysfunction. Therefore, we have studied whether any of these factors affects the ability of β-adrenoceptor agonists to relax rat bladder detrusor muscle in vitro. For this purpose we have compared male and female Wistar rats, young and old male Wistar rats, and male normotensive and spontaneously hypertensive rats (SHR). Comparisons were done using KCl-precontracted bladder strips (length about 15–20 mm) and the endogenous agonist noradrenaline, the synthetic non-subtype-selective agonist isoprenaline, and the prototypical β3-adrenoceptor agonists BRL 37,344 and CGP 12,177. While all agonists yielded numerically weaker relaxation in female as compared to male rats (for example for noradrenaline Emax 40±4% vs 53±6% relaxation, pEC50 5.41±0.13 vs 5.60±0.14), this difference reached statistical significance only for the weak partial agonist CGP 12,177. Responses to all agonists were attenuated in old as compared to young rats, largely due to a reduced maximum effect, although the difference did not reach statistical significance for isoprenaline. The maximum relaxation responses to noradrenaline and isoprenaline were significantly lower in SHR than in normotensive rats, but both strains exhibited similar responses to the partial agonist BRL 37,344. We conclude that factors associated with bladder dysfunction, such as gender, age and hypertension, can be associated with impaired β-adrenoceptor-mediated bladder relaxation. However, these alterations are not always consistent across various agonists, and the extent of the differences can be small. Therefore, we propose that β-adrenoceptor dysfunction may contribute to the pathophysiology of such conditions, but is unlikely to be the only or even the major factor in this regard. We speculate that β-adrenoceptor agonists may be effective in the treatment of bladder dysfunction under all of these conditions.
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页码:300 / 309
页数:9
相关论文
共 243 条
  • [1] Abrams P(2002)The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-committee of the International Continence Society Neurourol Urodyn 21 167-178
  • [2] Cardozo L(2003)Developmental changes in the functional, biochemical and molecular properties of rat bladder endothelin receptors Naunyn-Schmiedeberg’s Arch Pharmacol 367 462-472
  • [3] Fall M(2004)Urinary bladder contraction and relaxation: physiology and pathophysiology Physiol Rev 84 935-986
  • [4] Griffiths D(2005)The selectivity of β-adrenoceptor antagonists at the human β1, β2 and β3 adrenoceptors Br J Pharmacol 144 317-322
  • [5] Rosier P(1992)Adrenergic receptors and their signal transduction mechanisms in hypertension J Hypertens Suppl 10 S133-S145
  • [6] Ulmsten U(1995)Age-dependent changes in the β-adrenoceptor-G-protein(s)-adenylyl cyclase system in human right atrium J Cardiovasc Pharmacol 26 20-26
  • [7] Van KP(1997)Efferent and afferent neuronal hypertrophy associated with micturition pathways in spontaneously hypertensive rats Neurourol Urodyn 16 293-303
  • [8] Victor A(1996)Endogenous β3- but not β1-adrenergic receptors are resistant to agonist-mediated regulation in human SK-N-MC neurotumor cells Cell Signal 8 355-364
  • [9] Wein A(2000)Alterations in G-proteins and β-adrenergic responsive adenylyl cyclase in rat urinary bladder during aging J Pharmacol Exp Ther 294 969-974
  • [10] Afiatpour P(1997)Effect of pregnancy on rat myometrial beta 2-adrenoceptor mRNA and isoproterenol-induced relaxation of isolated uterine strips J Endocrinol 153 393-399