Endothelin (ET-1) is a potent
vasoconstrictor that plays an important role in the control of renal circulation and tubular function. The contribution of this
peptide to the pathogenesis of systemic
hypertension and
renal failure remains largely undefined. In spontaneously hypertensive rats (SHR) uninephrectomized at 20 weeks of age (UNX-SHR) and followed until 45 weeks of age, we determined ET-1 gene expression in renal tissue by reverse transcription-polymerase chain reaction and its localization by in situ hybridization in
paraffin-embedded kidney sections. Age-matched SHR and normotensive Wistar-Kyoto (WKY) rats were chosen as controls. At the end of the follow-up, UNX-SHR had high systolic blood pressure, intense
proteinuria, mesangial expansion, focal and segmental glomerular
sclerosis, and tubulointerstitial lesions. In relation to WKY and SHR, UNX-SHR exhibited an increase in ET-1 gene expression in renal cortex and medulla. By in situ hybridization and immunoperoxidase staining, an overexpression of ET-1 gene and
protein were seen in mesangial and glomerular epithelial cells and in some proximal tubules and vessels.
Angiotensin-converting enzyme (ACE) activity was significantly increased in the renal brush border. Since in mesangial cells,
angiotensin II induces ET-1 synthesis, a group of UNX-SHR received the
ACE inhibitor quinapril from the time of UNX. These animals had a decrease in blood pressure,
proteinuria, and serum and brush border ACE activity and in the expression and synthesis of ET-1 in all renal areas. On the whole, these data show that UNX-SHR have an upregulation of ET-1 gene and
protein in several structures of the kidney compared with SHR and WKY rats.
Quinapril diminished ACE activity and ET-1 expression and synthesis coincidentally with an improvement in
proteinuria and morphological lesions. The beneficial effects of
ACE inhibitors may be due to the diminution of both
angiotensin II and ET-1 generation.