Up-regulation of endothelin-converting enzyme during the development of transplant renal arteriosclerosis in human renal allografts

Tanabe, Shigeru; Ueda, Makiko; Han, Young-Sin; Kojima, Akiko; Nakatani, Tatsuya; Kishimoto, Toshifumi; Takahashi, Masaaki; Tanzawa, Kazuhiko

doi:10.1016/s0041-1345(96)00657-4

Cited by 15 publications

(6 citation statements)

References 8 publications

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“…The immediate and long‐term role of the renal ET system in kidney diseases, e.g. in patients with kidney transplants (Watchinger & Sayegh 1996, Tanabe et al . 1997) and in cyclosporine‐induced renal and systemic side‐effects (Fogo et al .…”

Section: Discussionmentioning

confidence: 99%

Endothelin synthesis and receptors in porcine kidney

Bäcker

Bokemeyer

Kramer

2001

Acta Physiologica Scandinavica

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As insufficient information on the endothelin (ET) system in the porcine kidney is available at present, we investigated renal ET-1 synthesis and ET receptors in this species. Because ET specifically affects renal and glomerular haemodynamics and distal tubular reabsorption, we studied ET-1 synthesis in isolated glomeruli and in inner medullary collecting duct (IMCD) cells and preproET-1 mRNA in renal cortex, isolated glomeruli and papillary tissue. In addition, we characterized density and properties of ET receptors in membranes from isolated glomeruli and papillary tissue. In contrast to isolated IMCD cells, which synthesized 120 +/- 11 fmol h(-1) mg-1 protein of ET-1, no such synthesis was found with isolated glomeruli in our assay system. Nevertheless, with RT-PCR preproET(-1) mRNA was clearly present in renal cortex and glomeruli as well as in papillary tissue. Glomerular membranes were found to have ET receptors with Bmax of 1.6 +/- 0.2 pmol mg-1 protein and Kd of 311 +/- 33 pmol L(-1). Using BQ-123 (10-5 M), a specific blocker of ETA receptors, we found that 58% of total receptors are ETA receptors. Thus, presumably 42% are ETB receptors (Bmax 0.7 +/- 0.1 pmol mg-1 protein; Kd 429 +/- 110 pmol L(-1)). Bosentan (10-5 M), an ETA- and ETB-receptor antagonist, blocked all ET receptors in glomerular membranes. Papillary membranes showed ET receptors with Bmax of 2.1 +/- 0.2 pmol mg-1 protein and Kd of 137 +/- 11 pmol L(-1). In the presence of BQ-123 (10-5 M) we found that all receptors are ETB receptors (Bmax 2.3 +/- 0.4 pmol mg-1 protein; Kd 162 +/- 25 pmol L(-1)). Bosentan (10-5 M) again blocked all ET receptors in papillary membranes, thus confirming our previous finding that IMCD cells possess high-affinity ETB receptors mediating the diuretic effects of ET. Thus, in the porcine kidney the ET system may act in an autocrine/paracrine manner at the glomerular as well as at the IMCD level.

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Section: Discussionmentioning

confidence: 99%

Endothelin synthesis and receptors in porcine kidney

Bäcker

Bokemeyer

Kramer

2001

Acta Physiologica Scandinavica

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“…It is possible, therefore, that in addition to increasing endothelin levels, NEP inhibition may increase levels of angiotensin II, which has been shown to be important in the development of IH in organ-cultured human saphenous vein. 23 Investigators of several studies have reported the expression of ECE in rat arterial injury models, 24,25 in human transplant arteriosclerosis, 26 and in human coronary atherosclerosis. 24 However, none to date have examined human saphenous vein.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of neointima formation in an organ culture of human saphenous vein: A comparison of dual endothelin-converting enzyme/neutral endopeptidase and selective neutral endopeptidase inhibition

Porter

Dickinson

London

2001

Journal of Vascular Surgery

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“…377"71 1.657"0.237* 1.70"0.39z 97"27 36"18 3.10"0.44* 1.06"0.23* 0.322"0.102z 32"39y TXqcombination treatment (ns12) 368"35 1.761"0.237 1.82"0.50z 92"26 38"8 3.00"0.46* 1.08"0.21* 0.341"0.089z 66"90* Data are mean"SD. TX, allograft; S Cr , serum creatinine.…”

mentioning

confidence: 99%

Combination treatment with an ETA-receptor blocker and an ACE inhibitor is not superior to the respective monotherapies in attenuating chronic transplant nephropathy in a 'Fisher-to-Lewis' rat model

Adams¹

2002

Nephrology Dialysis Transplantation

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We conclude that ET(A)-receptor blockade abrogates GS, tubulointerstitial and vascular damage in the 'Fisher-to-Lewis' model of CTN to a similar extent as ACE inhibition. However, only ACE inhibition inhibits glomerular hypertrophy. In contrast to ACE inhibition, the effect of ET(A)-receptor blockade is independent of BP. This finding is consistent with the notion that ET(A)-receptor mediated events play a partly BP-independent role in the genesis of CTN. Combination therapy exerts no additive nephroprotection.

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Up-regulation of endothelin-converting enzyme during the development of transplant renal arteriosclerosis in human renal allografts

Cited by 15 publications

References 8 publications

Endothelin synthesis and receptors in porcine kidney

Endothelin synthesis and receptors in porcine kidney

Inhibition of neointima formation in an organ culture of human saphenous vein: A comparison of dual endothelin-converting enzyme/neutral endopeptidase and selective neutral endopeptidase inhibition

Combination treatment with an ETA-receptor blocker and an ACE inhibitor is not superior to the respective monotherapies in attenuating chronic transplant nephropathy in a 'Fisher-to-Lewis' rat model

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