Increased endothelin excretion in rats with renal failure induced by partial nephrectomy

Abstract

1 Six weeks following partial nephrectomy in rats, significant increases in serum urea nitrogen and serum creatinine concentration and a significant decrease in creatinine clearance were observed. 2 Measurement of systolic blood pressure by tail plethysmography indicated that animals that had undergone partial nephrectomy were hypertensive. 3 Compared to sham-operated animals, there were 4 fold increases in both urinary protein excretion and urinary endothelin excretion. 4 There was a significant correlation between urinary protein and urinary endothelin excretion (r = 0.77). There was also a correlation (r = 0.65) between urinary endothelin excretion and systolic blood pressure.5 Plasma endothelin concentrations were not different in sham-operated and partially nephrectomized rats.6 The data indicate that there is an increased renal endothelin production in rats with chronic renal failure.

Increased Immunoreactive Endothelin-1 Levels in Blood Vessels and Glomeruli of Rats with Reduced Renal Mass

“…The results presented in this study are also consistent with recent reports suggesting that urinary ET-1 levels re flect renal production [13,14,30]. Based on our data, we propose that urinary ir-ET-l levels in rats with reduced renal mass reflect ET-1 overproduction in preglomcrular arteries and glomeruli.…”

“…Consistent with results from other investigators [14,25], and in keeping with data from nondialyzed patients with chronic renal failure [II], plasma ir-ET-1 level was un changed in rats with reduced renal mass. Flowever, in heniodialyzed patients, plasma ET-1 levels are increased [12].…”

“…12]. Elevated plasma ET-1 levels reported in he modialysis patients have been correlated with heightened blood pressure [12], In rats with reduced renal mass, in creased urinary ET-1 excretion correlated with hypertension as well as proteinuria and glomerulosclerosis [13,14], Chronic treatment of uremic rats with a selective ET,X re ceptor antagonist significantly blunted the rise of blood pressure and attenuated the development of glomeruloscle rosis [15]. These observations strongly support a role for ET-I in the pathogenesis of hypertension and the progres sion of renal insufficiency in chronic renal failure.…”

Endothelin in Chronic Renal Failure

“…Thus, urinary endothelin does not reflect plasma IR endothelin concentrations. Renal endothelin production was in creased in the rat with reduced renal mass [71], and endo thelin excretion was increased in rats with renal failure induced by partial nephrectomy [72], Therefore, increased endothelin production may be another possible cause of elevated plasma IR endothelin concentrations in patients with chronic renal failure. But it is not clear whether or not impaired kidneys of dialyzed patients could secrete endo thelin.…”

Role of endothelin in cardiovascular disease

“…Renal ET-1 generation correlated positively with glomerulosclerosis and urinary protein excretion in such animals. 166,167 Glomerular expression of ET A -and ET B -receptor mRNA is increased in experimental glomerulosclerosis. 168 Endothelin apparently participates in the induction and progression of sclerotic renal changes, leading to progression to end-stage renal disease.…”