Myocardial Expression of the Endothelin System in Endotoxin- Treated Rats

Although circulating plasma levels of endothelin (ET)-1 are elevated in endotoxemia, little is known about the myocardial expression of the ET system in endotoxic shock. We assessed the temporal mRNA expression pattern of key components of the ET system (pre-pro ET (ppET) -1, -2, ET-converting enzyme-1, ETA and ETB receptors) by reverse transcription polymerase chain reaction in a rat model of early endotoxic shock. Lipopolysaccharide (5 mg/kg, i.p.) caused a transient increase (p < 0.05) in inducible nitric oxide synthase mRNA expression. ppET-1 mRNA expression was increased at 2 h (~12-fold increase; p < 0.05) in the lipopolysaccharide compared with the saline group and ppET-2 mRNA expression was unaltered. ET-converting enzyme-1, ETA, and ETB receptor mRNA expression was unaltered in the lipopolysaccharide compared with the saline group. While ppET-1 mRNA expression is selectively upregulated in ventricular myocardium of lipopolysaccharide-treated rats, an absence of alteration in ET-converting enzyme-1 mRNA expression suggests an excess capacity of ET-converting enzyme-1 to cope with the increased expression of ET-1. At the level of the receptor, endotoxic shock did not affect the expression of either ETA or ETB receptor mRNA. These data are consistent with the increased expression of myocardial ET-1 as an acute-phase response due to hemodynamic instability associated with the early stages of endotoxic shock.