Effects of diabetes and diuresis on contraction and relaxation mechanisms in rat urinary bladder.
Experiments were designed to gain information on the mechanisms leading to diabetic urinary bladder dysfunction. Bladders from control rats, animals subjected to 4-5 wk streptozocin-induced diabetes, and rats subjected to equivalent diuresis produced by 5% sucrose feeding were studied with an in vitro whole-bladder preparation and neurochemical measurements. The diuretic group was used to distinguish alterations produced by metabolic effects on nerve and muscle from those induced by prolonged periods of excessive diuresis. Diuresis alone explains many of the diabetes-induced effects, including decreased norepinephrine levels, postsynaptic supersensitivity for sympathetic regulation of bladder storage, decreased responsiveness to parasympathetic regulation of emptying, and enhanced prostaglandin F2 alpha-induced contraction. Other diabetes-induced effects were not observed in the diuretic controls and are presumed to result from metabolic alterations associated with diabetes. These effects were decreases in norepinephrine uptake and in choline acetyltransferase activity, both markers of nerve terminal function. Thus, diuretic and metabolic factors appear to contribute to the early signs of parasympathetic and sympathetic neuropathy. In contrast, we found no evidence for loss of sensory nerve function in the diabetic bladder, at least at the organ level, because no diabetes- or diuresis-induced changes were observed in responsiveness to substance P or capsaicin.
Kudlacz
E M
EM
Division of Pharmacology, College of Pharmacy, Ohio State University, Columbus 43210.
Gerald
M C
MC
Wallace
L J
LJ
D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D015237:Dinoprost / Q000494:pharmacology; D004231:Diuresis; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*
D001626:Bethanechol Compounds; D011943:Receptors, Adrenergic, beta; D018723:Bethanechol; D000628:Aminophylline; D015237:Dinoprost; D002795:Choline O-Acetyltransferase; D007545:Isoproterenol; D009638:Norepinephrine