Endothelin peptides and receptors in human kidney

1. Animal kidneys are exquisitely sensitive to the vasoconstrictor and antinatriuretic effects of the endogenous vascular peptide endothelin. Animal studies have implicated endothelin in cyclosporin A and ischaemia-mediated renal damage. 2. In man, endothelin levels are raised in various disorders. Orally active endothelin antagonists are now being developed, but little was known of endothelin's role as a renal peptide in humans. These studies therefore aimed to characterize endothelin peptides and receptors ETA and ETB in human kidney, to direct potential therapeutic endeavours. 3. Ligand binding, immunocytochemical, radioimmunoassay and molecular biological studies were used to establish endothelin as a renal peptide in man. 4. The identification of species differences between man and rat directed further development of quantitative molecular biological methodology to permit analysis of endothelin receptors in human renal biopsies, and demonstrated perturbation of the system in the context of cyclosporin A therapy in renal transplantation.