Effect of diltiazem and pinacidil on the response of the rabbit urinary bladder to repetitive stimulation and in vitro ischemia

The effect of repetitive stimulation, in the presence and absence of diltia zem or pinacidil, on the contractile responses of isolated strips of rabbit bladder detrusor to field stimulation and carbachol, after 2 hr of incubat ion in a medium that serves as an in vitro model of ischemia (oxygen and su bstrate depleted Tyrode's solution), was determined. Our results are summar ized as follows: a) The magnitude of the contractile dysfunctions after in vitro ischemia was enhanced by repetitive stimulation. b) Pre-incubation of isolated strips of detrusor with diltiazem (50 mu M) inhibited the contrac tile responses to field stimulation (FS) and carbachol by 43 and 50%, respe ctively. Pinacidil (100 mu M) inhibited the contractile responses to FS and carbachol by 37 and 32%, respectively. c) Neither diltiazem nor pinacidil protected the bladder strips against the effects of 2 hr of incubation in i n vitro ischemia medium. However, d) both pinacidil and diltiazem reduced t he level of contractile dysfunctions induced by repetitive stimulation. In conclusion, the contractile response to FS was significantly more sensitive to in vitro ischemia and repetitive stimulation than was the contractile r esponse to carbachol. Both diltiazem and pinacidil protected the contractil e responses to FS and carbachol from the degenerative effects of repetitive stimulation, but not from the effects of in vitro ischemia. (C) 1999 Wiley -Liss, Inc.