Influence of age and bladder dysfunction on the contractile properties of isolated human detrusor smooth muscle

Abstract

To test the hypothesis that the in vitro contractile properties of human detrusor smooth muscle are dependent on the age, gender and lower urinary tract pathology of the patient. Contractions were elicited in isolated human detrusor smooth muscle preparations by nerve-mediated electrical field stimulation, agonist application (carbachol, α,β-methylene ATP and high-K solutions) or direct muscle electrical stimulation. Biopsies (n = 227) were obtained from four groups of patients with: stable bladders (control), bladder outlet obstruction (BOO), idiopathic (IDO), or neurogenic (NDO) detrusor overactivity. The magnitude of nerve-mediated contractions declined as a function of patients' age in each of the BOO, IDO and NDO groups but not in the control group. Contractions elicited by direct muscle activation (10 µM carbachol or electrical stimulation with 20 ms pulses in the presence of 1 µM tetrodotoxin) did not vary with patient age. Carbachol contractions were significantly smaller in samples from NDO bladders. Atropine resistance was more prevalent in the pathology groups compared with the control group and was greatest in the IDO group. There was no influence of age in the prevalence or magnitude of atropine-resistant contractions in any group. Muscle excitability to direct electrical stimulation was similar in all groups. In the human bladder there is no evidence for a decline of detrusor smooth muscle contractility or excitability as a function of age, nor any gender difference or presence of pathology. In the pathology groups there was evidence for a decline of functional innervation with age.