Antiplatelet and vasorelaxing actions of the acetoxy derivative of cedranediol isolated from Juniperus squamata

The antiplatelet and vasorelaxing actions of 14-acetoxycedrol, an acetyl derivative of the sesquiterpene 8,14-cedranediol isolated from Juniperus squamata Hayata, were investigated in washed rabbit platelets and rat aorta, respectively. 14-Acetoxycedrol inhibited the aggregation and ATP release of rabbit platelets induced by ADP, arachidonic acid, plateletactivating factor (PAF), collagen, and thrombin. Prolongation of the incubation time of 14-acetoxycedrol with platelets did not cause further inhibition and the aggregability of the treated platelets could be restored after washing of the platelets. It inhibited thromboxane B2 formation of washed platelets caused by arachidonic acid, collagen, and thrombin in a concentration-dependent manner. The formation of inositol phosphate caused by collagen and PAF was inhibited by 14-acetoxycedrol, while that caused by thrombin was not affected. 14-Acetoxycedrol markedly inhibited the intracellular calcium rise caused by PAF, and slightly inhibited that caused by thrombin in quin-2/AM-load platelets. In rat thoracic aortae, 14-acetoxycedrol inhibited the high K(+) (60 mM) and Ca(2+) (0.03 - 3 mM) induced cumulative contractions in a concentrationdependent manner, while it did not affect the phasic and tonic contractions elicited by norepinephrine. The tonic contractions elicited by KCl (60mM) and Bay K 8644 were also relaxed by 14-acetoxycedrol. It is concluded that the antiplatelet effect of 14-acetoxycedrol is due to the inhibition of thromboxane formation and phosphoinositides breakdown and the vasorelaxing action of 14-acetoxycedrol is due to inhibition of Ca(2+) influx through the voltage-dependent Ca(2+) channel.