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Effects of nifedipine and Bay K8644 on normal and hypertrophied rat detrusor
Author(s) -
Malmgren A.,
Andersson K.E.,
Andersson P.O.,
Fovaeus M.,
Sjögren C.
Publication year - 1988
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.1930070104
Subject(s) - bay k8644 , nifedipine , medicine , stimulation , endocrinology , tetrodotoxin , verapamil , detrusor muscle , calcium channel , calcium , agonist , urinary bladder , receptor
Bladder strip preparations from normal female Sprague‐Dawley rats as well as from rats with bladder outflow obstruction were mounted in organ baths, and isometric tension responses to electrical stimulation were recorded. Preparations of normal rat detrusor exhibited a minute spontaneous contractile activity. Addition of the calcium channel “agonist” Bay K8644 increased the basal tension and markedly enhanced spontaneous activity. In the presence of the drug the sensitivity to electrical field stimulation was enhanced; maximum amplitude increased, and the frequency producing 50% of maximum tension decreased. The calcium antagonist nifedipine had the opposite effects. In the presence of tetrodotoxin (TTX), the electrically induced responses were markedly depressed. Addition of Bay K8644 only partly restored these responses. Detrusor strips from rats with infravesical outflow obstruction exhibited marked spontaneous activity. They were less sensitive to electrical field stimulation than strips from normal bladder. Bay K8644 increased basal tension and spontaneous activity and also the maximum response to electrical stimulation. Nifedipine abolished spontaneous activity, induced a rightward shift of the frequency‐response curve, and decreased the maximum amplitude. Electrically induced responses were significantly more resistant to TTX than in normal detrusor, and in the presence of TTX addition of Bay K8644 increased electrically induced response to control level. Provided that TTX completely blocks nervous transmission and that Bay K8644 and nifedipine both have a preference for voltage‐operated calcium channels, these data suggest that hypertrophied bladder muscle has a nonspecific smooth muscle hypersensitivity to depolarizing stimuli. Possibly such changes can be linked to detrusor instability associated with outflow obstruction in man.