PROSTAGLANDIN-F2-ALPHA INDUCES CARDIAC MYOCYTE HYPERTROPHY IN-VITRO AND CARDIAC GROWTH IN-VIVO

Several prostaglandins [prostaglandin (PG) A(2), -B-2, -D-2, -E(2), -F -2 alpha, and -I-2 and carbaprostacyclin] and the thromboxane analogue U-46619 were analyzed for the ability to induce hypertrophy of rat ne onatal cardiac ventricular myocytes. Myocyte hypertrophy was induced s pecifically by PGF(2 alpha). Myocytes exposed to this prostanoid in cu lture increased in size and protein content. The contractile fibrils w ithin the cells became organized into parallel arrays, and the cells t ended to cluster and beat spontaneously. PGF(2 alpha) also induced the expression of c-fos, atrial natriuretic factor (ANF), and alpha-skele tal actin in these cells. The effects of PGF(2 alpha) were compared wi th several known cardiac myocyte hypertrophy factors (phenylephrine, e ndothelin-l, leukemia inhibitory factor, cardiotrophin-1, and angioten sin II). PGF(2 alpha) was found to be intermediate in potency among th e factors but induced a level of ANF production that was similar to 10 -fold higher than any of the other effecters. Responsiveness to PGF(2 alpha) was not limited to neonatal cardiocytes. Ventricular myocytes i solated from adult rats also responded specifically to PGF(2 alpha) wi th a morphological change similar to that observed with phenylephrine and by producing ANF. In rats, chronic administration of fluprostenol, a potent agonist analogue of PGF(2 alpha), resulted in a dose-depende nt increase in heart weight- and ventricular weight-to-body weight rat ios. The amount of PGF(2 alpha) extractable from the hearts of rats wi th cardiac hypertrophy induced by myocardial infarction was also found to be greater than that in sham-operated control rats. These results indicate that PGF(2 alpha) may play an important role in inducing card iac hypertrophy.