Contractile changes of the clitoral cavernous smooth muscle in female rabbits with experimentally induced overactive bladder

J Sex Med. 2008 May;5(5):1088-1096. doi: 10.1111/j.1743-6109.2008.00777.x. Epub 2008 Mar 4.

Abstract

Introduction: Recently, growing clinical evidence has suggested that sexual dysfunction is more prevalent in women with overactive bladder (OAB). Aims. However, there has been no basic research to clarify the relationship between OAB and female sexual dysfunction. Therefore, we investigated this issue using a rabbit model of OAB.

Methods: Twenty-seven New Zealand white female rabbits were randomly divided into the OAB and control groups.

Main outcome measures: The contractile responses of clitoral cavernous strips to K(+), phenylephrine (PE), Bay K 8644, and endothelin (ET)-1, and the relaxation responses of acetylcholine (ACh), sodium nitroprusside (SNP), and Y-27632 to PE-induced contraction by measuring isometric tension. Results. The contractile responses to K(+), PE, Bay K 8644, and ET-1 were significantly more increased in the OAB group in a dose-dependant manner than in the control group (P < 0.05), and the responses to ET-1 were more prominent than those to the remaining substances (P < 0.01). The increased contractile responses to ET-1 were blocked by BQ123 (ET(A) receptor antagonist) but not by BQ788 (ET(B) receptor antagonist). Clitoral cavernosal strips from the OAB group were more difficult to relax than those from the control group in terms of ACh- and SNP-induced relaxation (P < 0.05). The Y-27632-induced relaxant responses to PE- and ET-1-induced contraction were less prominent in the OAB group than in the control group. CONCLUSIONS; The results of this study provide evidence that female OAB may deteriorate clitoral engorgement, which is associated with a greater force generation by increased calcium sensitization and subsequently decreased of relaxation. The activation of ET and Rho-kinase system may be crucial to negatively effect the clitoral smooth muscle relaxation in experimentally induced OAB animal model. But whether these vasomotor effects are revived in human clitoris is still debatable.

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Acetylcholine / pharmacology
  • Adrenergic alpha-Agonists / pharmacology
  • Amides / pharmacology
  • Animals
  • Antihypertensive Agents / pharmacology
  • Calcium Channel Agonists / pharmacology
  • Clitoris / drug effects*
  • Clitoris / physiology
  • Dose-Response Relationship, Drug
  • Endothelin-1 / pharmacology
  • Female
  • Isometric Contraction / drug effects*
  • Isometric Contraction / physiology
  • Models, Animal
  • Muscle Relaxants, Central / pharmacology
  • Muscle Relaxation
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Nitroprusside / pharmacology
  • Oligopeptides / pharmacology
  • Peptides, Cyclic / pharmacology
  • Phenylephrine / pharmacology
  • Piperidines / pharmacology
  • Potassium
  • Pyridines / pharmacology
  • Rabbits
  • Urinary Bladder, Overactive / chemically induced*
  • Urinary Bladder, Overactive / physiopathology
  • Vasodilator Agents / pharmacology

Substances

  • Adrenergic alpha-Agonists
  • Amides
  • Antihypertensive Agents
  • Calcium Channel Agonists
  • Endothelin-1
  • Muscle Relaxants, Central
  • Oligopeptides
  • Peptides, Cyclic
  • Piperidines
  • Pyridines
  • Vasodilator Agents
  • Y 27632
  • Nitroprusside
  • Phenylephrine
  • BQ 788
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Acetylcholine
  • Potassium
  • cyclo(Trp-Asp-Pro-Val-Leu)