Negative inotropic effect of basic fibroblast growth factor on adult rat cardiac myocyte

Circulation. 1997 Oct 21;96(8):2501-4. doi: 10.1161/01.cir.96.8.2501.

Abstract

Background: Basic fibroblast growth factor (bFGF) is highly expressed in the myocardium in some cardiac disorders, such as ischemia-reperfusion and cardiac allograft rejection. However, whether bFGF has any effects on myocardial contraction is unknown.

Methods and results: We examined the effects of bFGF on myocardial contractility using isolated adult rat cardiac myocyte preparations. bFGF exerted a direct negative inotropic effect that was concentration and time dependent. The pretreatment of myocytes with a neutralizing anti-bFGF antibody (100 ng/mL) abolished the negative inotropic effects of bFGF (100 ng/mL). Platelet-derived growth factor (12.5 ng/mL) and transforming growth factor-beta (1 ng/mL) did not exert such effects, which indicated that bFGF-induced negative inotropism was considered to be specific for this growth factor. bFGF decreased the peak intracellular Ca2+ transient by 46% during systole. The enhanced production of nitric oxide was unlikely to be responsible for the bFGF-induced negative inotropic effect.

Conclusions: bFGF, primarily a potent growth promoter, produced acute negative inotropic effects in the adult cardiac myocyte that could have resulted from alterations in intracellular Ca2+ homeostasis. The negative inotropic effect of bFGF may contribute to myocardial dysfunction associated with ischemia-reperfusion injury and heart transplant rejection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Depression, Chemical
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Fibroblast Growth Factor 2 / pharmacology*
  • Heart / drug effects*
  • Myocardial Contraction / drug effects*
  • Myocardium / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Rats

Substances

  • Enzyme Inhibitors
  • Fibroblast Growth Factor 2
  • Calcium
  • NG-Nitroarginine Methyl Ester