Abstract
The effect of administration of N-desulfated/acetylated heparin, almost completely devoid of anticoagulant activity, on the progression of renal disease was examined in rats with 13/4 nephrectomy. Three groups of rats with 13/4 nephrectomy were studied. Group I (control, n = 11) received 0.15 ml of 0.15 M NaCl subcutaneously twice daily for 5 wk; group 2 (n = 11) received 0.15 ml twice daily of N-desulfated/acetylated heparin (5.4 mg/ml; less than 0.5 U/ml); group 3 (n = 9) received 0.15 ml twice daily of standard beef lung heparin (5.4 mg/ml; 977 U/ml). Clearances and renal histological studies were done at the end of 5 wk of heparin or saline administration. Rats given the heparin preparations had significantly higher inulin clearances (2.55 +/- 0.38 ml/min per body weight (BW) for group 2, or 2.60 +/- 0.24 ml/min per kg BW for group 3) than control rats (1.59 +/- 0.20 ml/min per kg BW). Histological analysis revealed a greater number of glomeruli with segmental or global sclerosis, hyalinosis, or fibrosis (36.6%) in control rats than in rats receiving N-desulfated/acetylated heparin (6.2%) or standard heparin (3.0%). Blood pressure averaged 169.4 +/- 6.2 mmHg in controls, 119.1 +/- 6.1 in rats of group 2, and 124.3 +/- 2.5 in rats of group 3. The values for blood pressure were significantly lower in the two groups receiving heparin than in controls. These studies indicate that a heparin preparation, almost completely devoid of anticoagulant properties, affords the same degree of protection against progression of renal disease as does standard heparin in rats with subtotal renal ablation. It is suggested that other biological properties of heparin may be responsible for the effects observed.
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- BITTER T., MUIR H. M. A modified uronic acid carbazole reaction. Anal Biochem. 1962 Oct;4:330–334. doi: 10.1016/0003-2697(62)90095-7. [DOI] [PubMed] [Google Scholar]
- Castellot J. J., Jr, Beeler D. L., Rosenberg R. D., Karnovsky M. J. Structural determinants of the capacity of heparin to inhibit the proliferation of vascular smooth muscle cells. J Cell Physiol. 1984 Sep;120(3):315–320. doi: 10.1002/jcp.1041200309. [DOI] [PubMed] [Google Scholar]
- Castellot J. J., Jr, Hoover R. L., Harper P. A., Karnovsky M. J. Heparin and glomerular epithelial cell-secreted heparin-like species inhibit mesangial-cell proliferation. Am J Pathol. 1985 Sep;120(3):427–435. [PMC free article] [PubMed] [Google Scholar]
- Clowes A. W., Karnowsky M. J. Suppression by heparin of smooth muscle cell proliferation in injured arteries. Nature. 1977 Feb 17;265(5595):625–626. doi: 10.1038/265625a0. [DOI] [PubMed] [Google Scholar]
- Diamond J. R., Karnovsky M. J. Nonanticoagulant protective effect of heparin in chronic aminonucleoside nephrosis. Ren Physiol. 1986;9(6):366–374. doi: 10.1159/000173102. [DOI] [PubMed] [Google Scholar]
- Fishman J. A., Karnovsky M. J. Effects of the aminonucleoside of puromycin on glomerular epithelial cells in vitro. Am J Pathol. 1985 Mar;118(3):398–407. [PMC free article] [PubMed] [Google Scholar]
- Guyton J. R., Rosenberg R. D., Clowes A. W., Karnovsky M. J. Inhibition of rat arterial smooth muscle cell proliferation by heparin. In vivo studies with anticoagulant and nonanticoagulant heparin. Circ Res. 1980 May;46(5):625–634. doi: 10.1161/01.res.46.5.625. [DOI] [PubMed] [Google Scholar]
- Hoover R. L., Rosenberg R., Haering W., Karnovsky M. J. Inhibition of rat arterial smooth muscle cell proliferation by heparin. II. In vitro studies. Circ Res. 1980 Oct;47(4):578–583. doi: 10.1161/01.res.47.4.578. [DOI] [PubMed] [Google Scholar]
- Hök M., Riesenfeld J., Lindahl U. N-[3H]Acetyl-labeling, a convenient method for radiolabeling of glycosaminoglycans. Anal Biochem. 1982 Jan 15;119(2):236–245. doi: 10.1016/0003-2697(82)90580-2. [DOI] [PubMed] [Google Scholar]
- Inoue Y., Nagasawa K. Selective N-desulfation of heparin with dimethyl sulfoxide containing water or methanol. Carbohydr Res. 1976 Jan;46(1):87–95. doi: 10.1016/s0008-6215(00)83533-8. [DOI] [PubMed] [Google Scholar]
- KOLETSKY S., GOODSITT A. M. Natural history and pathogenesis of renal ablation hypertension. Arch Pathol. 1960 Jun;69:654–662. [PubMed] [Google Scholar]
- Nasjletti A., Malik K. U. Renal kinin-prostaglandin relationship: implications for renal function. Kidney Int. 1981 Jun;19(6):860–868. doi: 10.1038/ki.1981.90. [DOI] [PubMed] [Google Scholar]
- Olson J. L. Role of heparin as a protective agent following reduction of renal mass. Kidney Int. 1984 Feb;25(2):376–382. doi: 10.1038/ki.1984.27. [DOI] [PubMed] [Google Scholar]
- Purkerson M. L., Hoffsten P. E., Klahr S. Pathogenesis of the glomerulopathy associated with renal infarction in rats. Kidney Int. 1976 May;9(5):407–417. doi: 10.1038/ki.1976.50. [DOI] [PubMed] [Google Scholar]
- Purkerson M. L., Joist J. H., Greenberg J. M., Kay D., Hoffsten P. E., Klahr S. Inhibition by anticoagulant drugs of the progressive hypertension and uremia associated with renal infarction in rats. Thromb Res. 1982 May 15;26(4):227–240. doi: 10.1016/0049-3848(82)90287-0. [DOI] [PubMed] [Google Scholar]
- Purkerson M. L., Joist J. H., Yates J., Valdes A., Morrison A., Klahr S. Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation. Proc Natl Acad Sci U S A. 1985 Jan;82(1):193–197. doi: 10.1073/pnas.82.1.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenberg R. D. Biologic actions of heparin. Semin Hematol. 1977 Oct;14(4):427–440. [PubMed] [Google Scholar]
- Shimamura T., Morrison A. B. A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats. Am J Pathol. 1975 Apr;79(1):95–106. [PMC free article] [PubMed] [Google Scholar]
- Tollefsen D. M., Majerus D. W., Blank M. K. Heparin cofactor II. Purification and properties of a heparin-dependent inhibitor of thrombin in human plasma. J Biol Chem. 1982 Mar 10;257(5):2162–2169. [PubMed] [Google Scholar]
