a) Discuss role of endothelin system in health and kidney diseases. [4] b) Role of endothelin receptor antagonists in various kidney diseases. [6]
The endothelin system comprises potent vasoactive peptides, primarily endothelin-1 (ET-1), which regulate vascular tone, cell proliferation, and inflammation. In the kidney, the endothelin system modulates glomerular hemodynamics, sodium and water excretion, and fibrogenesis (Brenner & Rector's The Kidney, 11th ed, Ch. 98).
ET-1 is synthesized by endothelial and renal epithelial cells and acts via two G-protein coupled receptors: ETA and ETB.
| Receptor | Location | Function |
|---|---|---|
| ETA | Vascular smooth muscle | Vasoconstriction, proliferation, inflammation |
| ETB | Endothelium, renal tubules | Vasodilation (via NO, PGI2), clearance of ET-1 |
In health, ET-1 maintains renal vascular tone and promotes natriuresis via ETB receptors. In kidney diseases, ET-1 is upregulated, contributing to:
- Vasoconstriction → ischemia, glomerular hypertension
- Mesangial proliferation and matrix expansion → glomerulosclerosis
- Inflammation and fibrosis via cytokine induction
ET-1 overexpression is implicated in diabetic nephropathy, hypertensive nephrosclerosis, chronic kidney disease (CKD), and acute kidney injury (AKI) (Brenner & Rector's The Kidney, 11th ed).