Experimental hyperreflexia: effect of intravesical administration of various agents.
In anesthetized rabbits, we can induce a significant degree of spontaneous activity in the urinary bladder by placing a ligature around the proximal portion of the external urethra. Previous studies characterized the activity as primarily reflex in nature, since intravesical hexamethonium selectively inhibited the hyperreflexia. In this current study we determined the effect of intravesical administration of a variety of compounds to inhibit the induced hyperreflexia. The following agents were tested at concentrations of 1, 10, 100 and 500 mumol/l (intravesically): verapamil, cromakalim, nifedipine, diltiazem, and atropine; lidocaine was tested in 0.05, 0.5 and 5% solutions. The results are summarized as follows: (1) Lidocaine was the most effective agent tested, virtually eliminating both the amplitude and frequency of the spontaneous activity at the lowest concentration (0.5%). (2) Verapamil and nifedipine were somewhat more potent than cromakalim and diltiazem. Atropine sulfate was the least potent, inhibiting both the amplitude and frequency of the hyperreflexia by less than 50% at 500 mumol/l. (3) In all cases, the amplitude of the spontaneous activity was inhibited to a significantly greater degree than the frequency of the spontaneous activity. (4) In general, there was no effect of any of the agents on mean arterial pressure at 1 or 10 mumol/l. At 100 and 500 mumol/l, all agents except for lidocaine and cromakalim decreased arterial pressure. These two agents produced no consistent fall in blood pressure at any concentration. In conclusion, the acute hyperreflexic (rabbit) preparation provides a highly reproducible and consistent model for the study of the effect of drugs on hyperreflexia.(ABSTRACT TRUNCATED AT 250 WORDS)
Levin
R M
RM
Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia.
Kitada
S
S
Hayes
L
L
Kau
S T
ST
Fromm-Freeck
S
S
Howe
B B
BB
Wein
A J
AJ
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D019806:Cromakalim; D004110:Diltiazem / Q000494:pharmacology; D004558:Electric Stimulation; D004576:Electromyography; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D012018:Reflex / Q000187:drug effects*; D001745:Urinary Bladder Diseases / Q000139:chemically induced* / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D001578:Benzopyrans; D006584:Hexamethonium Compounds; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine