Prevention of Diabetic Glomerulopathy by Pharmacological Amelioration of Glomerular Capillary Hypertension

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1986 Jun 1

PMID 3011862

Citations 206

Authors

R Zatz

B R Dunn

T W Meyer

S Anderson

H G Rennke

B M Brenner

Affiliations

Soon will be listed here.

Abstract

Two groups of adult male Munich-Wistar rats and a third group of nondiabetic age-matched and weight-matched normal control rats underwent micropuncture study 1 mo, and morphologic studies 14 mo, after induction of streptozotocin diabetes or sham treatment. All animals were fed standard rat chow. Diabetic rats received daily ultralente insulin to maintain stable moderate hyperglycemia (approximately 350 mg/dl). In addition, one group of diabetic rats was treated with the angiotensin I converting enzyme inhibitor, enalapril, 15 mg/liter of drinking water. Average kidney weight, whole kidney and single-nephron glomerular filtration rate, and glomerular plasma flow rate were elevated to similar values in both groups of diabetic rats, relative to normal control rats. Non-enalapril-treated diabetic rats exhibited significant elevations in mean glomerular capillary hydraulic pressure and transcapillary hydraulic pressure gradient, compared with the other groups studied, and only this group eventually developed marked and progressive albuminuria. Likewise, histological examination of the kidneys at 14 mo disclosed a high incidence of glomerular structural abnormalities only in non-enalapril-treated diabetic rats. These findings indicate that prevention of glomerular capillary hypertension in rats with diabetes mellitus effectively protects against the subsequent development of glomerular structural injury and proteinuria. This protection is afforded despite pronounced hyperglycemia and elevated levels of glucosylated hemoglobin, further supporting our view that hemodynamic rather than metabolic factors predominate in the pathogenesis of diabetic glomerulopathy.

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References

Landis E, Jonas L, Angevine M, Erb W . THE PASSAGE OF FLUID AND PROTEIN THROUGH THE HUMAN CAPILLARY WALL DURING VENOUS CONGESTION. J Clin Invest. 1932; 11(4):717-34. PMC: 435847. DOI: 10.1172/JCI100445. View

Drury P . Diabetes and arterial hypertension. Diabetologia. 1983; 24(1):1-9. DOI: 10.1007/BF00275938. View

Mogensen C, Christensen C . Predicting diabetic nephropathy in insulin-dependent patients. N Engl J Med. 1984; 311(2):89-93. DOI: 10.1056/NEJM198407123110204. View

Ditzel J, Junker K . Abnormal glomerular filtration rate, renal plasma flow, and renal protein excretion in recent and short-term diabetics. Br Med J. 1972; 2(5804):13-9. PMC: 1789055. DOI: 10.1136/bmj.2.5804.13. View

Jensen P, Christiansen J, Steven K, Parving H . Renal function in streptozotocin-diabetic rats. Diabetologia. 1981; 21(4):409-14. View

Longhurst J, CAPONE R, Zelis R . Evaluation of skeletal muscle capillary basement membrane thickness in congestive heart failure. Chest. 1975; 67(2):195-8. DOI: 10.1378/chest.67.2.195. View

Hostetter T, Rennke H, Brenner B . The case for intrarenal hypertension in the initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982; 72(3):375-80. DOI: 10.1016/0002-9343(82)90490-9. View

Olson J, de Urdaneta A, HEPTINSTALL R . Glomerular hyalinosis and its relation to hyperfiltration. Lab Invest. 1985; 52(4):387-98. View

Hostetter T, Troy J, Brenner B . Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int. 1981; 19(3):410-5. DOI: 10.1038/ki.1981.33. View

10.

Viets J, Deen W, Troy J, Brenner B . Determination of serum protein concentration in nanoliter blood samples using fluorescamine or 9-phthalaldehyde. Anal Biochem. 1978; 88(2):513-21. DOI: 10.1016/0003-2697(78)90451-7. View

11.

Parving H, Smidt U, Friisberg B, Bonnevie-Nielsen V, Andersen A . A prospective study of glomerular filtration rate and arterial blood pressure in insulin-dependent diabetics with diabetic nephropathy. Diabetologia. 1981; 20(4):457-61. DOI: 10.1007/BF00253407. View

12.

Mancini G, Carbonara A, Heremans J . Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965; 2(3):235-54. DOI: 10.1016/0019-2791(65)90004-2. View

13.

Zatz R, Meyer T, Rennke H, Brenner B . Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy. Proc Natl Acad Sci U S A. 1985; 82(17):5963-7. PMC: 390674. DOI: 10.1073/pnas.82.17.5963. View

14.

Rasch R . Control of blood glucose levels in the streptozotocin diabetic rat using a long-acting heat-treated insulin. Diabetologia. 1979; 16(3):185-90. DOI: 10.1007/BF01219796. View

15.

Steffes M, Brown D, MAUER S . Diabetic glomerulopathy following unilateral nephrectomy in the rat. Diabetes. 1978; 27(1):35-41. DOI: 10.2337/diab.27.1.35. View

16.

Baylis C, Deen W, Myers B, Brenner B . Effects of some vasodilator drugs on transcapillary fluid exchange in renal cortex. Am J Physiol. 1976; 230(4):1148-58. DOI: 10.1152/ajplegacy.1976.230.4.1148. View

17.

Parving H, Andersen A, Smidt U, Christiansen J, Oxenboll B, Svendsen P . Diabetic nephropathy and arterial hypertension. The effect of antihypertensive treatment. Diabetes. 1983; 32 Suppl 2:83-7. DOI: 10.2337/diab.32.2.s83. View

18.

Zatz R, Brenner B . Pathogenesis of diabetic microangiopathy. The hemodynamic view. Am J Med. 1986; 80(3):443-53. DOI: 10.1016/0002-9343(86)90719-9. View

19.

Viberti G, Keen H . The patterns of proteinuria in diabetes mellitus. Relevance to pathogenesis and prevention of diabetic nephropathy. Diabetes. 1984; 33(7):686-92. DOI: 10.2337/diab.33.7.686. View

20.

Mogensen C . Glomerular filtration rate and renal plasma flow in short-term and long-term juvenile diabetes mellitus. Scand J Clin Lab Invest. 1971; 28(1):91-100. DOI: 10.3109/00365517109090667. View