Factors responsible for acetylcholine-induced dilatation in the isolated perfused rat kidney

Mechanism of acetylcholine (ACh)-induced dilatation was investigated in isolated perfused rat kidney. Under a constant flow of 8–10 ml/min, ACh (0.001–3 μg/0.1 ml) caused a dose-dependent decrease in perfusion pressure raised by submaximum concentration of phenylephrine (PE). ACh-induced dilatations were inhibited by atropine (10⁻⁶ mol/l), hexamethonium (10⁻⁴ mol/l), indomethacin (10⁻⁵ mol/l), methylene blue (10⁻⁵ mol/l), N^G-nitro-l-arginine (l-NOARG, 10⁻⁴ mol/l), tetrodotoxin (TTX, 10⁻⁶ mol/l), capsaicin (10⁻⁶ mol/l), and glibenclamide (10⁻⁵ mol/l). These results suggest that in the isolated perfused rat kidney, endothelium-derived hyperpolarizing factor (EDHF), nitric oxide (NO), and tachykinin neuromediators may play a role in ACh-induced dilatation via stimulation of guanylate cyclase and opening of ATP-sensitive potassium channels.