Prostaglandin F2 alpha induces cardiac myocyte hypertrophy in vitro and cardiac growth in vivo.

Several prostaglandins [prostaglandin (PG) A2, -B2, -D2, -E2, -F2 alpha, and -I2 and carbaprostacyclin] and the thromboxane analogue U-46619 were analyzed for the ability to induce hypertrophy of rat neonatal cardiac ventricular myocytes. Myocyte hypertrophy was induced specifically by PGF2 alpha. Myocytes exposed to this prostanoid in culture increased in size and protein content. The contractile fibrils within the cells became organized into parallel arrays, and the cells tended to cluster and beat spontaneously. PGF2 alpha also induced the expression of c-fos, atrial natriuretic factor (ANF), and alpha-skeletal actin in these cells. The effects of PGF2 alpha were compared with several known cardiac myocyte hypertrophy factors (phenylephrine, endothelin-1, leukemia inhibitory factor, cardiotrophin-1, and angiotensin II). PGF2 alpha was found to be intermediate in potency among the factors but induced a level of ANF production that was approximately 10-fold higher than any of the other effectors. Responsiveness to PGF2 alpha was not limited to neonatal cardiocytes. Ventricular myocytes isolated from adult rats also responded specifically to PGF2 alpha with a morphological change similar to that observed with phenylephrine and by producing ANF. In rats, chronic administration of fluprostenol, a potent agonist analogue of PGF2 alpha, resulted in a dose-dependent increase in heart weight- and ventricular weight-to-body weight ratios. The amount of PGF2 alpha extractable from the hearts of rats with cardiac hypertrophy induced by myocardial infarction was also found to be greater than that in sham-operated control rats. These results indicate that PGF2 alpha may play an important role in inducing cardiac hypertrophy.
AuthorsJ Lai, H Jin, R Yang, J Winer, W Li, R Yen, K L King, F Zeigler, A Ko, J Cheng, S Bunting, N F Paoni
JournalThe American journal of physiology (Am J Physiol) Vol. 271 Issue 6 Pt 2 Pg. H2197-208 (Dec 1996) ISSN: 0002-9513 [Print] UNITED STATES
PMID8997275 (Publication Type: Journal Article)
Chemical References
  • Prostaglandins
  • Prostaglandins F, Synthetic
  • RNA, Messenger
  • Phenylephrine
  • fluprostenol
  • Atrial Natriuretic Factor
  • Dinoprost
  • Aging (physiology)
  • Animals
  • Animals, Newborn
  • Atrial Natriuretic Factor (biosynthesis, genetics)
  • Cardiomegaly (chemically induced, pathology)
  • Cells, Cultured
  • Dinoprost (pharmacology)
  • Heart (drug effects, growth & development)
  • Male
  • Myocardial Infarction (metabolism)
  • Myocardium (metabolism, pathology)
  • Phenylephrine (pharmacology)
  • Prostaglandins (pharmacology)
  • Prostaglandins F, Synthetic (pharmacology)
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors

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