Atropine Resistance of Transmurally Stimulated Isolated Human Bladder Muscle

Abstract

Human detrusor strips were obtained from patients undergoing reimplantation of ureters because of reflux, transvesical prostatectomy, or cysto-urethrectomy en bloc because of bladder malignancy. The strips were electrically stimulated. A frequency-dependent contractant response was obtained that was potentiated by physostigmine and abolished by tetrodotoxin. The maximum response approximately equaled that of acetylcholine in a maximum concentration. In most bladder preparations from patients without known functional bladder disturbances, atropine (0.01 to 0.1 microM) had a marked inhibitory effect, and at concentrations exceeding 1 microM the blockade was complete. In strips obtained from patients undergoing transvesical prostatectomy, and who also had a cystometrically verified unstable bladder, there was a varying degree of atropine resistance, with some preparations showing a 50 per cent resistance to atropine. Prazosin, phentolamine, yohimbine, guanethidine, clonidine, and noradrenaline had no consistent effects on the electrically induced bladder contraction. Nifedipine and nimodipine caused a maximum of 65 per cent inhibition of the response. Addition of nimodipine to atropine-resistant strips when maximum atropine inhibition had been reached abolished the contractions. Omitting calcium from the bath solution rapidly abolished the electrically induced contraction. It is suggested that in the normal human bladder the contraction induced by electrical stimulation is mainly atropine sensitive. However, in the functionally disturbed bladder, part of the bladder contraction is atropine resistant, a finding that may have clinical implications.

Structural and Functional Denervation of Human Detrusor after Spinal Cord Injury

“…No significant atropine-resistant neuromuscular transmission was present and in essence all the residual contraction was also resistant to tetrodotoxin, indicating that it was due to direct muscle stimulation rather than nerve stimulation and neurotransmitter release. Atropine virtually eliminates nerveinduced contraction in normal human bladder Sjogren et al, 1982), but noncholinergic nonadrenergic (NANC) neuromuscular communication is present in several other species. Atropine-resistance in humans has been reported in some pathological conditions (Saito et al, 1993;Sjogren et al, 1982), but such findings could actually have been due to direct muscle stimulation.…”

“…Atropine virtually eliminates nerveinduced contraction in normal human bladder Sjogren et al, 1982), but noncholinergic nonadrenergic (NANC) neuromuscular communication is present in several other species. Atropine-resistance in humans has been reported in some pathological conditions (Saito et al, 1993;Sjogren et al, 1982), but such findings could actually have been due to direct muscle stimulation. NANC neurotransmission may be more prevalent with lowfrequency EFS (Brading and Williams, 1990;Luheshi and Zar, 1990), with the cholinergic component predominating at higher frequencies.…”

“…Excitatory neuromuscular transmission in the normal human bladder is predominantly cholinergic (Brindley and Craggs, 1976;Chen et al, 1994;Sibley, 1984;Sjogren et al, 1982), but a wide range of putative transmitters is present. These include nitric oxide (NO) (Smet et al, 1994), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP), and tachykinins (Smet et al, 1997).…”

Potent contractile activity of endothelin on the human isolated urinary bladder

“…To date, expression of the pre-proendothelin messenger RNA has been reported only in the vascular endothelium and the potential physiological meaning of these findings is only a matter of speculation. The action of endothelin was substantially atropine-resistant which excludes a significant participation of the cholinergic nerves, the major excitatory innervation of the normal human bladder (Sjogren et al, 1982;Sibley, 1984;Maggi et al, 1988). Further, we found that the action of endothelin is totally resistant to nifedipine at a concentration that abolished the KCI-induced contractions.…”

Isolation and individual electrical stimulation of single smooth-muscle cells from the urinary bladder of the pig

“…In the literature dealing with the smooth muscle of the urinary bladder, there is an ongoing discussion about the pathways via which electrical field stimulation Of bladder strips in vitro leads to contraction and whether direct stimulation of the cells is possible (Cowan & Daniel, 1982;Sjogren et al, 1982;Sibley, 1984;Kinder & Mundy, 1985). In this series of experiments, we have shown that single cells contract in response to direct electrical stimulation, provided that the pulse duration is 5.0 ms or longer, and this implies that direct stimulation of bladder strips should be possible.…”