Urinary Bladder Relaxation Through Activation of Imidazoline Receptors Induced by Agmatine is Increased in Diabetic Rats

ABSTRACTObjectivesThe effect of agmatine on bladder contractility and the diabetes‐induced alteration of this action were studied in the rat.MethodsBladder strips were isolated from 9‐week‐old streptozotocin (STZ)‐diabetic rats and control Wistar rats. Strips were hung in an organ bath for measurement of isometric tension and pre‐contracted with either 1 µmol/L acetylcholine (ACh) or 50 mmol/L KCl. Dose‐dependent relaxation of the bladder strips was studied by cumulative administration of agmatine 1–100 µmol/L into the organ bath. Effects of specific imidazoline receptor (IR) antagonists on the agmatine‐induced relaxation were studied. Western blotting analysis was used to measure bladder IR, sulphonylurea receptor (SUR) and inwardly rectifying K+ channel subunit 6.2 (Kir 6.2) protein levels.ResultsAgmatine reduced ACh and KCl pre‐contracted bladder strip tension in a dose‐dependent fashion. Relaxation was significantly increased in STZ‐diabetic rats. The relaxation was inhibited by BU224, a selective I2 IR antagonist; but not by efaroxan (I1 IR antagonist) or KU14R (I3 IR antagonist). Moreover, the agmatine‐induced relaxation was attenuated by glibenclamide (inhibitor of KATP channel) and H‐89 (inhibitor of protein kinase A), but enhanced by 3‐isobutyl‐1‐methylxanthine (IBMX, inhibitor of cyclic AMP phosphodiesterase). Western blotting showed increased expression of bladder IR but not SUR or Kir 6.2 in the STZ‐diabetic rat.ConclusionAgmatine causes rat bladder relaxation by activation of the I2 IR, which opens KATP channels through the cyclic AMP/protein kinase A pathway. Agmatine‐induced bladder relaxation in STZ‐diabetic rats is increased due to a higher expression of IR.