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

Abstract

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 Ca²⁺ entry into aortic smooth muscle cells

after noradrenaline-induced depletion of intracellular Ca²⁺. 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 Ca²⁺, noradrenaline (1 μM) was added to stimulate the aortic contraction

in the Ca²⁺-free medium. After the intracellular Ca²⁺ was completely depleted, the

aortic strips were washed 3 times with Ca²⁺-free medium. Upon addition of Ca²⁺, 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) (Ca²⁺ 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 Ca²⁺ channels or Ca²⁺ entry due to α-adrenoceptor

activation.