Analysis of the in vitro pharmacologic response of renal pelvis and detrusor smooth muscle to thiphenamil, oxybutynin and verapamil.
A new computerized methodology was used to acquire and analyze the relative pharmacologic sensitivity of the renal pelvis and urinary bladder of the rabbit to pharmacologic stimulation. Comparison was made of the effects of thiphenamil, verapamil and oxybutynin on the spontaneous contractions of isolated detrusor and renal pelvis. Data collected by computer were evaluated in terms of amplitude, frequency, and tension change to varying concentration of pharmacologic stimulation. Data were analyzed using a frequency/time domain algorithm developed specifically to evaluate the contribution of the oscillatory components of tension associated with smooth muscle tissues. For the renal pelvis the results show 6 X 10(-5) M thiphenamil, 10(-3) M oxybutynin, and 5 X 10(-6) M verapamil resulted in a 50% inhibition of the phasic contractions. Thiphenamil significantly increased the contractile frequency of the renal pelvis. For the bladder 10(-3) M thiphenamil resulted in a 50% inhibition of the phasic contractions, while 3 X 10(-4) M oxybutynin and 3 X 10(-6) M verapamil were needed to achieve the same level of inhibition. Thiphenamil at lower doses (10(-4) M to 5 X 10(-4) M) showed a biphasic effect--an increase of the bladder tissue activity followed by a relaxation phase--that oxybutynin and verapamil failed to produce. The results show that the calcium blocker suppresses the spontaneous activity of the upper and lower urinary tract at lower concentrations than the anticholinergic or thiphenamil.
Levounis
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P
Stanford University Medical School, Calif.
Constantinou
C E
CE
D000818:Animals; D004158:Diphenylacetic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007682:Kidney Pelvis / Q000187:drug effects*; D008297:Male; D008333:Mandelic Acids / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D011817:Rabbits; D013457:Sulfur Compounds; D001743:Urinary Bladder / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology*
D004158:Diphenylacetic Acids; D008333:Mandelic Acids; D013457:Sulfur Compounds; D014700:Verapamil; C009488:thiphenamil; C005419:oxybutynin