INCREASED IMMUNOREACTIVE ENDOTHELIN-1 LEVELS IN BLOOD-VESSELS AND GLOMERULI OF RATS WITH REDUCED RENAL MASS

Elevated plasma and urinary endothelin-1 (ET-1) levels have been repor ted in patients with renal failure as well as in remnant kidney models of chronic renal failure. We investigated whether these changes are r elated to increased ET-1 production in cardiovascular and renal tissue s of rats with reduced renal mass, In uremic rats, systolic blood pres sure rose in parallel with the progression of renal insufficiency. At week 6, changes in systolic blood pressure were positively correlated with serum creatinine levels (r = 0.728, p < 0.01). Plasma immunoreact ive ET-1 (ir-ET-1) concentration was similar in uremic rats and sham-o perated controls. In contrast, urinary ir-ET-1 excretion was significa ntly greater in uremic rats and was correlated with the elevation of s erum creatinine and proteinuria (r = 0.795, and 0.922, p < 0.01, respe ctively). Compared to the controls, ir-ET-1 concentration in the thora cic aorta, preglomerular arteries and glomeruli were 1.4-, 3.5- and 6. 7-fold higher, respectively, in uremic rats (p < 0.01) than in the con trols. However, ir-ET-1 concentration in the mesenteric arterial bed a nd the left ventricle remained similar in the 2 groups, whereas it was significantly lower in the renal papilla of uremic rats (p < 0.01). T hus, ET-1 production is unchanged or slightly increased in extrarenal cardiovascular tissues of rats with reduced renal mass. In contrast, E T-1 production is significantly augmented in preglomerular arteries an d glomeruli, but reduced in the papilla, suggesting that increased uri nary ir-ET-1 excretion in uremic rats reflects ET-1 overproduction in the former renal tissues. Elevated ET-1 production in blood vessels an d glomeruli may thus play a key role in the aggravation of hyper tensi on and the progression of renal insufficiency in this rat remnant kidn ey model of chronic renal failure.