Pharmacological comparison of the isolated whole urethra model to urethral strip methodology.
Urethral strips provide a sensitive method for quantitative pharmacology; however, it is not clear if the physiological response of the whole urethra to pharmacological agents can be extrapolated from these data. The intent of this study was to investigate whether the linear contraction of strips is consistent with the ability of the intact urethra to alter resistance to flow. To measure the effect of drugs on the ability of the intact urethra to alter resistance to flow in the absence of endogenous influences, we developed an in vitro whole rabbit urethra model. We characterized the effect of norepinephrine in the absence and presence of alpha-adrenergic antagonists (prazosin, yohimbine, and LY253352) on intraurethral pressure which was measured during constant saline infusion using a Statham pressure transducer. We compared this to the contractile function of urethral strips. The pA2 values for alpha-adrenergic antagonists, LY253352, prazosin, and yohimbine were 8.17 +/- 1.5, 6.49 +/- 1.2, and 5.58 +/- 0.9, respectively, as determined in the whole urethra. The pA2 values for these antagonists determined in urethral strips were as follows: LY253352 8.72 +/- 1.2; prazosin 7.52 +/- 1.5, and yohimbine 5.6 +/- 0.84. Pharmacologically, the whole urethra model and isolated strips appeared to respond similarly to alpha-adrenergic agonists and antagonists, and thus both models would be suitable for pharmacological studies on the normal urethra.
Chun
A L
AL
Division of Urology, University of Pennsylvania School of Medicine, Philadelphia.
Gill
H S
HS
Wein
A J
AJ
Levin
R M
RM
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008954:Models, Biological; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D013565:Sympatholytics / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D013678:Technology, Pharmaceutical / Q000379:methods*; D014521:Urethra / Q000502:physiology*
D013565:Sympatholytics; D013566:Sympathomimetics; D009638:Norepinephrine