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      Alteration of Endothelin-1 Concentration in STZ-Induced Diabetic Rat Nephropathy

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          Background: Recently, an endothelin (ET-1) with a potent vasoconstrictive activity and stimulative activity of vascular muscular cell growth was discovered and blood ET-1 levels were higher in diabetic patients than in healthy subjects, suggesting that high ET-1 levels assist development and progression of diabetic microangiography. Methods: We examined renal function, and serum and tissue ET-1 levels in streptozotocin (STZ)-induced diabetic rats treated with a prostaglandin (PG) I<sub>2</sub> derivative to investigate the effect of PGI<sub>2</sub> in diabetic vascular disturbance. Results: Renal weight, urinary albumin, urinary N-acetyl-β, D-glucosaminidase (NAG) and serum ET-1 levels increased in STZ-induced diabetic rats, and a tendency to increase in renal tissue ET-1 levels was observed. Furthermore, electron-microscopic findings in the kidneys showed mesangial cell proliferation and mesangial matrix expansion which might be caused by diabetic nephropathy. The PGI<sub>2</sub> derivative reduced urinary albumin and NAG levels in STZ-induced rats. It was considered, therefore, that the PGI<sub>2</sub> derivative is effective in diabetic nephropathy. As the PGI<sub>2</sub> derivative also reduced renal tissue ET-1 levels, improvement of diabetic nephropathy partially was considered to result from the reduction of renal tissue ET-1 levels. Conclusion: In STZ-induced rats, increased serum ET-1 levels and a tendency to increase in renal tissue ET-1 levels were associated with increases in urinary albumin and NAG levels, and these levels were decreased by a PGI<sub>2</sub> derivative. These findings suggested that increased ET-1 concentrations assist development and progression of diabetic nephropathy, especially diabetic microangiopathy, and the PGI<sub>2</sub> derivative may be effective for inhibition of diabetic microangiopathy mediated by reduction of ET-1 concentrations.

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          Most cited references 3

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          Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: Identity of human and porcine endothelin

          A cDNA encoding a human endothelium-derived vasoconstrictor peptide, endothelin, was isolated from a human placenta cDNA library. The nucleotide sequence of this cDNA clone showed that the primary structure of the human preproendothelin has 212 amino acid residues and is highly homologous to porcine preproendothelin, and that human endothelin is identical with porcine endothelin.
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            Presence of immunoreactive endothelin in human plasma.

             Y Hirata,  T. Emori,  K Ando (1989)
            A highly specific and sensitive radioimmunoassay has been established for measurement of human endothelin (hET) in human plasma. After extraction of plasma with an octyl-silica column, this assay allowed for detection of immunoreactive (IR) hET as low as 0.2 fmol/ml. In 16 healthy subjects, the mean concentration of plasma IR-hET was 0.6 fmol/ml. Reverse-phase HPLC coupled with radioimmunoassay revealed two major IR-hET components, one corresponding to authentic hET(1-21) and another with more hydrophilicity than hET(1-21). These data indicate that ET is a circulating vasoconstrictor hormone in man.
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              A thromboxane A2 synthetase inhibitor retards hypertensive rat diabetic nephropathy


                Author and article information

                Horm Res Paediatr
                Hormone Research in Paediatrics
                S. Karger AG
                14 March 2002
                : 56
                : 5-6
                : 165-171
                Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan
                48113 Horm Res 2001;56:165–171
                © 2002 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 3, References: 30, Pages: 7
                Original Paper


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