Article

Research in Experimental Medicine

, Volume 197, Issue 4, pp 177-187

First online:

Leukotriene receptor blockade in experimental heart failure

  • Michael PfeiferAffiliated withKlinik und Poliklinik für Innere Medizin II, Universitätsklinikum
  • , Frank MudersAffiliated withKlinik und Poliklinik für Innere Medizin II, Universitätsklinikum
  • , Andreas LuchnerAffiliated withKlinik und Poliklinik für Innere Medizin II, Universitätsklinikum
  • , Friedrich BlumbergAffiliated withKlinik und Poliklinik für Innere Medizin II, Universitätsklinikum
  • , Günter A. J. RieggerAffiliated withKlinik und Poliklinik für Innere Medizin II, Universitätsklinikum
  • , Dietmar ElsnerAffiliated withKlinik und Poliklinik für Innere Medizin II, Universitätsklinikum

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Abstract

The pathophysiological role of endogenous leukotrienes in cardiovascular control and the regulation of renal function in congestive heart failure is not known. Therefore, in six conscious dogs with or without heart failure induced by right ventricular pacing (270/min, 10 days) we studied the effects of the leukotriene receptor antagonist FPL55712 on hemodynamics, plasma hormones and renal function. In healthy dogs, FPL55712 (1 mg kg−1 + 0.01 mg kg−1 min−1 i. v.) had little effect on hemodynamics, only reducing heart rate by 11% and insignificantly increasing systemic vascular resistance. Plasma levels of norepinephrine (−57%), renin (−30%) and aldosterone (−24%) were significantly decreased. Renal function parameters were not changed. In dogs with heart failure, FPL55712 significantly increased systemic vascular resistance (+16%) and decreased cardiac output (−15%). Plasma hormone levels were not changed, but renal plasma flow was decreased (−13%) and glomerular filtration rate (+12%), renal vascular resistance (+13%) and filtration fraction (+23%) were increased. It is concluded that there is no evidence for a contribution of endogenous leukotrienes to the systemic vaso-constriction in experimental heart failure. Whether the increase in systemic and renal vascular resistance induced by the leukotriene antagonist in dogs with heart failure reflects a role for endogenous leukotrienes with vasodilator action is still unclear and deserves further investigation.

Key words

Heart failure Leukotrienes FPL55712 Neurohormones