Effects of Synthetic Cu 18-08, Cu 18-10 and Cu 18-11 Compounds on Ca2+ Mobilization into Smooth Muscle of Isolated Rat Aorta

Previously, we demonstrated that CU 18-08, CU 18-10, acyl aniline derivatives as well as CU 18-11, an acyl aminopyridine derivative reduced the spontaneous contraction of rat duodenum. In this study, we investigated the effect of these three synthetic compounds on the Ca 2+ entry into aortic smooth muscle cells after noradrenaline-induced depletion of intracellular Ca 2+ . Thoracic aortic strips were isolated from male Wistar rats (250-300g), denuded the endothelium layer, and suspended in a 15 ml organ bath containing physiological solution. To deplete intracellular Ca 2+ , noradrenaline (1 μM) was added to stimulate the aortic contraction in the Ca 2+ -free medium. After the intracellular Ca 2+ was completely depleted, the aortic strips were washed 3 times with Ca 2+ -free medium. Upon addition of Ca 2+ , the spontaneous contraction or resting tone (RT) of rat aortic strip was observed again. This process was inhibited by prazosin ( 1 μM) ( α-adrenoceptor antagonist) and nifedipine (1 μM) (Ca 2+ entry blocker). Our results showed that CU 18-08 (10 μM) and CU 18-10 ( 10 μM) significantly inhibited the RT while CU 18-11 did not. These findings suggested that CU 18-08 and CU 18-10 interfered the mechanical refilling process of into intracellular pools. It is possible that these two compounds may have pharmacological effect on voltage-operated Ca 2+ channels or Ca 2+ entry due to α-adrenoceptor activation.