Inhibitory effect of streptozotocin-induced diabetes on non-cholinergic motor transmission in rat detrusor and its prevention by sorbinil.
1. Non-cholinergic motor transmission in the urinary bladder of streptozotocin (STZ)-diabetic rats was studied by recording contractile activity of strips of detrusor in vitro. 2. The neurogenic contractile responses to electrical field stimulation (EFS) of atropine-treated detrusor strips were decreased in 4, 8 and 12 week STZ-diabetic rats. The decrease was most marked in 12 week diabetic rats and least in 4 week ones. 3. Concentration-response curves showed no change in sensitivity of the detrusor to acetylcholine (ACh) in diabetic rats. The maximum tension generated by ACh was similar in diabetic and non-diabetic animals. 4. The contractile responses to EFS at frequencies greater than or equal to 1 Hz were not maintained during stimulation. The 'fade' was significantly greater in detrusor strips of diabetic rats. 5. The contractile response of detrusor to EFS was significantly greater in 12 week diabetic rats treated with the aldose reductase inhibitor sorbinil, than in untreated 12 week diabetic rats. The sensitivity to ACh was similar in the two groups. 6. It is concluded that the reduction of the neurogenic non-cholinergic responses of detrusor to EFS in STZ-diabetic rats is probably caused by a reduction in the release of the non-cholinergic motor transmitter. The results are discussed in relation to bladder dysfunction in human diabetes mellitus.
Luheshi
G N
GN
Department of Pharmacological Sciences, Medical School, Newcastle Upon Tyne.
Zar
M A
MA
D000109:Acetylcholine / Q000494:pharmacology; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation; D016055:Urinary Retention / Q000188:drug therapy
D001786:Blood Glucose; D007093:Imidazoles; D048289:Imidazolidines; D000449:Aldehyde Reductase; C026411:sorbinil; D000109:Acetylcholine