Upregulation of renal endothelin receptors in rats with cyclosporine A-induced nephrotoxicity

“…The exact role played by ET in CsA-induced vasoconstriction is uncertain. A number of investigators have demonstrated an increase in urinary ET excretion in rats after acute CsA infusion (10,11). The study of Bunchman et al ( 12) showing concentration-dependent CsA induction of ET synthesis in cultured endothelial cells would indicate that CsA may directly stimulate increased ET activity in the systemic or renal vasculature.…”

Section: Introductionmentioning

confidence: 99%

Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles.

Lanese¹,

Conger²

1993

J. Clin. Invest.

205

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Recent evidence suggests that the potent constrictor peptide, endothelin (ET) has a mediating role in cyclosporine A (CsA)-related renal vasoconstriction. However, the nature of the CsA-ET interaction and effect on the renal vasculature is uncertain. The purpose of the present study was twofold: (a) to determine if CsA exposure caused direct local release of ET from the endothelium of the renal microvasculature and (b) to determine if locally generated ET has paracrine effects on the underlying vascular smooth muscle to induce vasoconstriction. Experiments were performed in isolated rat renal arterioles. First it was determined that both afferent arteriole (AA) and efferent arteriole (EA) exhibited concentration-dependent decreases in lumen diameter to increasing molar concentrations of CsA. The AA was more sensitive to the vasoconstrictive effects of CsA than the EA. Next, the blocking effect of a recently synthesized putative ETA receptor antagonist was verified in both the AA and EA, where it was found that the cyclic peptide cyclo D-Asp-L-Pro-D-Val-L-Leu-D-Trp totally inhibited the vasoconstriction observed with ET addition. Finally, the role of locally stimulated ET in CsA-induced vasoconstriction was tested by determining the effect of the ETA receptor antagonist on CsA-induced AA and EA constriction. In the AA the vasoconstrictor effect of 1011 M CsA was completely blocked by the ETA receptor antagonist. However, in contrast to AA, 10 1 M CsA in EA in the presence of the ETA receptor antagonist decreased EA lumen diameter by a mean of 41% from baseline (4.80±0.75 ,um vs 7.80±0.84 ,tm, P < 0.05). This change in lumen diameter was similar to that induced by CsA alone. These data suggest that CsA directly constricts renal microvessels. This effect is mediated by ET in the AA but not the EA. (J.

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“…[13][14][15] Endothelin receptors are distributed in a variety of cells and tissues in different proportions, suggesting potentially opposite regulatory functions. Endothelin receptor expression is up-regulated by ischemia, 16 cyclosporin, 17 and interleukin-1␤ (IL-1␤). 18 Production of endothelin or endothelin receptor knock-out mice allowed the evaluation of the role and biologic significance of different members of the endothelin family.…”

Section: Introductionmentioning

confidence: 99%

Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops

Guruli

Pflug

Pecher

et al. 2004

Blood

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Upregulation of renal endothelin receptors in rats with cyclosporine A-induced nephrotoxicity

Cited by 97 publications

References 5 publications

Vasoconstrictor endothelin receptors characterized in human renal artery and vein in vitro

Vasoconstrictor endothelin receptors characterized in human renal artery and vein in vitro

Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles.

Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops

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