P. Nambi et al., ENDOTOXIN-MEDIATED CHANGES IN PLASMA ENDOTHELIN CONCENTRATIONS, RENALENDOTHELIN RECEPTOR AND RENAL-FUNCTION, Pharmacology, 48(3), 1994, pp. 147-156
The purpose of these studies was to examine the changes in renal endot
helin (ET) receptor, renal function and plasma ET (ET-1) concentration
in male Sprague-Dawley rats injected with nonlethal doses of Escheric
hia coli endotoxin (LPS). Prior to the injection of LPS, kidney ET rec
eptor density was 59 +/- 5 fmol/mg protein (n = 20). At 24 h after the
injection of 1 or 3 mg/kg LPS, [I-125]ET-1 binding to kidney membrane
s was increased by 70% in both LPS groups (p < 0.001). Scatchard analy
sis of the saturation binding experiments confirmed that the increase
in ([)125)I]ET-1 binding was due to an increase in receptor density wi
th no change in affinity (202 pmol/l at baseline and 168 pmol/1 and 24
6 pmol/l at 24 h after the injection of 1 and 3 mg/kg LPS, respectivel
y). At 7 days after the injection of LPS, kidney ET-1 receptor density
was still increased by 30 +/- 5% and 58 +/- 16%, respectively (p < 0.
05, compared to the baseline value). Baseline values for Na+ and K+ ex
cretion were approximately 115 mu Eq/h and 214 +/- mu Eq/h respectivel
y, and were decreased with LPS. Maximal decreases in Na+ and K+ excret
ion occurred at 48 h (-85%) and 30 h (-82%), respectively, following t
he injection of 3 mg/kg LPS and returned to baseline levels in 7 days.
Following the injection of 3 mg/kg LPS, plasma immunoreactive ET-1, a
s measured by radioimmunoassay, increased in a time-dependent manner:
the maximal increase of 60% occurred within 1 h after the injection of
LPS (p < 0.05), and thereafter returned to baseline levels. Kidney ti
ssue levels of ET-1 increased from baseline values of 2.6 fmol/mg prot
ein to a peak of 4.6 fmol/mg protein 1 h after the injection of LPS. T
issue ET-1 levels were still significantly elevated at 6 h but not 24
h after LPS injection. These studies suggest that ET-1, either by incr
eases in plasma concentration and/or altered receptor density, may be
involved in the LPS-induced impairment of renal function.