Effect of K+ Channel Openers, KRN2391 and Ki1769, and Nitroglycerin on the Urinary Tract of Rats In Vivo

Abstract

The effects of KRN2391 (N-cyano-N’-(nitroxyethyl)-3-pyridine carboximidamide methanesulfonate), which possesses ATP-sensitive potassium (K+) channel opening (KCO) activity and nitrate activity; Ki1769 (N-cyano-N′-(phenylethyl)-3-pyridinecarboximidamide methanesulfonate), which possesses only KCO activity; and nitroglycerin (NG) were determined on the motility of the ureter, urinary bladder and urethra of rats. Bladder contraction was induced by infusion of fluid into the bladder of conscious rats and recorded on a cystometrogram. KRN2391 and Ki1769 (both 0.3 mg/kg, i.v.) prolonged the micturition interval immediately after the injection, but NG (5 mg/kg, i.v.) did not. Peristaltic movement of the ureter, recorded in anesthetized rats, was inhibited by i.v. injection of KRN2391 and Ki1769 (both 0.03 mg/kg). However, when NG, NaN02, N-nitro L-arginine methylester and methylene blue were applied directly to the ureter, no change in movement of the ureter was detected. KRN2391 (0.03 mg/kg, i.v.) and Ki1769 (0.3 mg/kg, i.v.) reduced the resistance to fluid infusion through the urethral lumen in anesthetized rats, whereas NG (0.5 mg/kg, i.v.) only reduced this resistance transiently. These results indicate that KCO activity had an inhibitory effect on the motility of the ureter, bladder and urethra. On the other hand, nitrate activity had an inhibitory effect on urethral tonus, corresponding to that induced by KCO activity.