The role of Hexose Monophosphate Pathway (HMP) in cardiac hypertrophy

30 THE ROLE OF HEXOSE MONOPHOSPHATE PATHWAY(HMP) IN CARDIAC HYPERTROPHY. A. Kizu, K. Nakamura,*M. Fujiwara, H. Okamori, I. Kimura, M. Yasumi, T. Minaga, M. Tanaka and H. Ijichi. 2nd Dept. of Med., Kyoto Pref. Univ. of Med., Kyoto and *Akashi Municipal Hospital, Akashi, Japan In order to evaluate biochemical alterationsincardiac hypertrophy of rats subjected to isoproterenol(ISP) injection or banding of ascending aorta, experiments were conducted on whole heart, isolated cardiac myocytes and non-myocytes obtained from hypertrophied heart. [Whole heart]; Ventricular G6PDH and 6PGDH activities were significantly increased 24 hrs after treatment. Following twice administration of ISP, these activities were elevated to be maximum coincided with remarkable prolifera tion of fibroblasts in myocardium, and thereafter returned to normal range. Similar patterns were observed in rats subjected to banding of aorta. 14 On the other hand, decarboxylation from lC-glucose in ventricular slices obtaiyfd from ISP treated rats accelerated cmpared with 6C-glucose as substrate. These phenomena were associated with increase in RNA content and DNA dependent RNA polymerase activation in their time course. [Isolated cardiac myocytes and non-myocytes]; Specific activity of GGPDH in non-myocyte fraction was 2.2 times higher than that of myocyte fraction in normal rat heart. Definite difference in both fractions was maintained during G6PDH activity elevation following ISP injection, while maximum elevation of enzyme activity in myocytes was observed earlier than in non-myocyte fraction. Those enzyme activities remarkably suppressed by injection of cycloheximide. The isozyme pattern of GGPDH were also determined using Davis's method and revealed to be composed of four elevation in activities of all isozymes were isozymes, demonstrated to be intensified in zymogram after ISP injection. Above all, the fourth band from cathod was mainly participated in non-myocyte fraction. These results indicate that HMP is activated in the process of myocardial hypertrophy and this activation of HMP is principally associated with increased synthesis of RNA and these alterations were considered to be reasonable in their time sequence. Participation of non-myocytes for biochemical alteration in cardiac hypertrophy should be also emphasized as far as G6PDH induction is concerned. In biochemical aspects in myocardium, role of non-mYocYte should be studied more intensively in details in future.