COOLING-INDUCED BLADDER CONTRACTION: STUDIES ON ISOLATED DETRUSOR MUSCLE PREPARATIONS IN THE RAT SEHAM M. D. MUSTAFA AND OLAV THULESIUS ABSTRACT Objectives. Detrusor muscle contraction and uninhibited micturition after intravesical instillation of ice water is interpreted as a sign of upper motor neuron lesions. The basic mechanism of cooling-induced contraction (CIC) at the level of smooth muscle, however, has not been satisfactorily explained. We therefore designed model experiments with cooling of rat detrusor muscle. Methods. We recorded isometric tension from strips of rat urinary detrusor muscle in organ baths during stepwise cooling. CIC was tested before and after addition of various standard agents interfering with known neurogenic (autonomic blockers, tetrodotoxin, capsaicin) and myogenic mechanisms of contraction (calcium channel blockers). Results. Stepwise cooling (37° to 5°C) of detrusor muscle induced reproducible graded contractions, inversely proportional to temperature. CIC was not dependent on a neural mechanism (not blocked by tetrodotoxin or capsaicin) or the release of neurotransmitters but was linked to translocation of calcium. It was reduced by calcium channel blockers and Ca 2+ -free solution. Blockage of the Ca 2+ -adenosine triphos- phatase pump, which inhibits the extrusion of calcium, also plays a significant role in the process and enhances CIC. Conclusions. Cooling of detrusor muscle preparations induces a graded myogenic contraction inversely pro- portional to the temperature. The mechanism is not dependent on local nervous control but is related to calcium translocation. UROLOGY 53: 653–657, 1999. © 1999, Elsevier Science Inc. All rights reserved. U ninhibited reflex micturition after intravesical instillation of cold water is considered a sign of spinal damage. Detrusor contraction in conjunc- tion with bladder cooling is supposed to be initi- ated by sensory mucosal receptor stimulation fol- lowed by detrusor activation though a spinal reflex within the sacral segments. An ice-water test is used clinically in the evaluation of neurogenic dis- orders of continence as part of a standard urody- namic examination in the differential diagnosis of overactive bladder subtypes. In a positive ice-water test, bladder contraction is followed by uninhib- ited micturition caused by upper motor neuron damage. 1–3 Sustained detrusor contraction on bladder cooling has been found in neurologically normal children but not in children with recurrent urinary tract infection that may be due to bladder muscle damage. 4 However, the basic mechanism underlying cooling-induced detrusor muscle con- traction is poorly understood. We recently found that isolated vascular and bronchial smooth muscle preparations react with forceful contraction when subjected to cooling. This response is not mediated by a neurogenic mech- anism but is due to a blockage of the intracellular and extracellular calcium transport mechanisms. 5,6 To our knowledge the basic mechanism of the thermal detrusor smooth muscle control has not been investigated. It was therefore the objective of this study to clarify the response of smooth muscle cooling in isolated detrusor muscle preparations. MATERIAL AND METHODS PREPARATION OF BLADDER STRIPS Male Wistar rats, weighing 200 to 250 g, were killed by decapitation. The urinary bladder was removed and placed in Krebs solution of the following composition (mM): sodium From the Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Safat, Kuwait Reprint requests: Seham M. D. Mustafa, M.D., Department of Pharmacology and Toxicology, Faculty of Medicine, P.O. Box 24923, Safat, 13110 Kuwait Submitted: July 13, 1998, accepted (with revisions): September 29, 1998 BASIC SCIENCE © 1999, ELSEVIER SCIENCE INC. 0090-4295/99/$20.00 ALL RIGHTS RESERVED PII S0090-4295(98)00568-8 653