Abstract
HWA 285 expected to have an anti-arteriosclerotic activity for its inhibitory action on the cyclic AMP phosphodiesterase. The inhibitory activity on the enzyme resulted in improving vasodilative function and erythrocyte deformity as well as repressing platelet coagulation. We have investigated the anti-arteriosclerotic activity of HWA 285 on the following study using arteriosclerotic rabbits: histochemical examinations of six structural components from aorta and one biophysical characteristics of aorta, i. e., the pulse wave velocity (PWV).
Material and methods: twenty eight Japanese albino domesticated rabbits, 38 months old male, were divided into three groups; 13 rabbits for healthy group (H), 9 for arteriosclerosis (S) and 6 for HWA 285 treated (A). Lesions on both intima and media in aorta were made by nitrogen inhalation, intramuscular injection of norepinephrine and cholesterol peroral ingestion. Group A received one dose of HWA 285, 3mg/kg/day, through intravenous injection at the same time the load test was started. An external loop of carotid artery was made and used for measuring both PWV and blood pressure. All animals were sacrificed 16 weeks later and examined for the following items in their thoracic media by MSP method; smooth muscle cell (SMC), nuclear DNA (DNA), elastin (EL), collagen (CL), acid mucopolysacharides (AMPS), glycoprotein (GP) and calcium phosphate (CA). The differences in the six structural materials among three groups were evaluated with the principale component analysis.
Results: The H group showed PWV between 7 and 8m/sec and the S group exhibited it gradual increase to 9m/sec. Whereas, the A group had a declining trend in PWV and significantly lower values than that of the S group (p<0.001). The average regression coefficiencies for the H, S and A group were 0.0109, 0.0626, and -0.056m/sec/ wk, respectively. The S group clearly showed some lesions on SMC, reduction in the amount of EL and CL, increase in diseased connective tissues and deposition of CA under histochemical studies. Among the A group, however in both tissues and the amount of components were observed only in slight. Since HWA 285 has more than three times of efficacy than its analogue, pentoxifylline, further clinical evaluation on this drug should be forthcoming. Besides HWA 285 has the anti-arteriosclerotic function observed in this study, we believe that it has some activity which acts directly on metabolism in smooth muscle cells of aortic wall and connective tissues.
