Laboratory Investigation

Kidney International (1987) 32, 652–663; doi:10.1038/ki.1987.257

The influence of concomitant experimental hypertension and glomerulonephritis

Roland C Blantz, Francis Gabbai, Leslie C Gushwa and Curtis B Wilson

Department of Medicine, Veterans Administration Medical Center and School of Medicine, University of California, San Diego, and Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California USA

Correspondence: Roland C Blantz MD, Veterans Administration Medical Center, 111H, 3350 La Jolla Village Drive, San Diego, California 92161, USA.

Received 30 May 1986; Revised 22 March 1987; Re-revised 22 June 1987.

Top

Abstract

The influence of concomitant experimental hypertension and glomerulonephritis. Utilizing the two kidney–one clip Goldblatt model (CH), we have examined the influence of hypertension upon the course of antiglomerular basement membrane antibody-induced glomerulonephritis (GN) over a period of 10 to 14 weeks after induction of CH and GN, utilizing evaluations in the awake rat by renal micropuncture of the undipped kidney and morphologic analysis (control [C], GN, CH, and GN+CH). Metabolic studies revealed that GN and GN+CH rats developed proteinuria, elevations in serum creatinine and blood pressure (P <0.05). GN+CH resulted in significant reductions in two kidney glomerular filtration rate (GFR) below values in C, and GFR in the undipped kidney was markedly reduced when compared to CH. The glomerular capillary hydrostatic pressure and the pressure gradient (DeltaP) were elevated approx4 to 5 mm Hg in GN and CH rats and 6 mm Hg above GN and CH values in the GN+CH rats. The glomerular ultrafiltration coefficient (LpA) was reduced to approx40% of C in both GN and GN+CH in spite of further increases in DeltaP. Surface nephron filtration rate was similar in all groups, suggesting glomerular dysfunction was primarily in nephrons below the surface in GN+CH. Morphologic evaluation revealed that GN+CH exhibited a combination of diffuse and focally sclerotic lesions characteristic of GN and CH, respectively. Documented further increases in PG did not worsen glomerular morphology, but kidney GFR did decrease. Hypertension induced deterioration of glomerular function in nephrons below the surface was not associated with marked morphologic deterioration, but a combination of the characteristics of GN and CH.

Top

References

  1. Baldwin DS: Chronic glomerulonephritis: Nonimmunologic mechanisms of progressive glomerular damage. Kidney Int 21:109–120, 1982
  2. Neugarten J, Feiner HD, Schacht RG, Gallo GR, Baldwin DS: Aggravation of experimental glomerulonephritis by superimposed clip hypertension. Kidney Int 22:257–263, 1982 | PubMed | ISI | ChemPort |
  3. Okuda S, Onoyama K, Fujima S, Yukinori O, Nomoto K, Omae T: Influence of hypertension on the progression of experimental autologous immune complex nephritis. J Lab Clin Med 101:461–471, 1983 | PubMed | ISI | ChemPort |
  4. Raij L, Azar S, Keane W: Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats. Kidney Int 26:1372–143, 1984
  5. Motoki K, Kusuyama Y, Ueno Y, Miyamoto Y, Nishio I, Masuyama Y: Chronic nephrotoxic nephritis in spontaneously hypertensive rats. Jap Heart J 19:662–664, 1978
  6. Knowlton AL, Stoerk H, Seegal BC, Loeb EN: Influence of adrenal cortical steroids upon the blood pressure and the rate of progression of experimental nephritis in rats. Endocrinology 38:315–324, 1946
  7. Tikkanen I, Fyhrquist F, Miettinen A, Tornroth T: Autologous immune complex nephritis and DOCA-NaCl load: a new model of hypertension. Acta Pathol Microbiol. Scand [À] 88:241–250, 1980
  8. Iversen BM, Ofstad J: Effect of hypertension on experimental glomerulonephritis in rats. Lab Invest 50:163–173, 1984 | PubMed | ISI | ChemPort |
  9. Hostetter TH, Olson JL, Rennke RG, Venkatachalam MA, Brenner BM: Hyperfiltration in remnant nephrons: A potentially adverse response to renal ablation. Am J Physiol 241:F85–F93, 1981 | PubMed | ISI | ChemPort |
  10. Hostetter TH, Troy JL, Brenner BM: Glomerular hemodynamics in experimental diabetes mellitus. Kidney Int 19:410–415, 1981 | PubMed | ISI | ChemPort |
  11. Tomford RC, Karlinslky ML, Buddington B, Alfrey AC: Effect of thyrOparathyroidectomy and parathyroidectomy on renal function and the nephrotic syndrome in rat nephrotoxic serum nephritis. J Clin Invest 68:655–664, 1981 | PubMed |
  12. Maddox DA, Bennett CM, Deen WM, Glassock RJ, Knutson D, Daugharty TM, Brenner BM: Determinants of glomerular filtration in experimental glomerulonephritis in the rat. J Clin Invest 55:305–318, 1975 | PubMed |
  13. Blantz RC, Wilson CB: Acute effects of anti-glomerular basement membrane antibody on the process of glomerular filtration in the rat. J Clin Invest 58:899–911, 1976 | PubMed |
  14. Blantz RC, Tucker BJ, Wilson CB: The acute effects of antiglomerular basement membrane antibody upon glomerular filtration rate in the rat. II. Influence of dose and complement depletion. J Clin Invest 61:910–921, 1978
  15. Ichikawa I, Hoyer JR, Seiler MW, Brenner BM: Mechanism of glomerulotubular balance in the setting of heterogeneous glomerular injury. J Clin Invest 69:185–198, 1982 | PubMed | ISI |
  16. Steiner RW, Tucker BJ, Gushwa LC, Gifford J, Wilson CB, Blantz RC: Glomerular hemodynamics in moderate Goldblatt hypertension in the rat. Hypertension 4:51–57, 1982
  17. Gabbai FB, Gushwa LC, Peterson OW, Wilson CB, Blantz RC: Analysis of the renal function in the two kidney Goldblatt model. Am J Physiol 252:F131–F137, 1987
  18. Schwietzer G, Gertz KH: Changes of hemodynamics and glomerular ultrafiltration in renal hypertension of rats. Kidney Int 15:134–143, 1979 | PubMed | ISI | ChemPort |
  19. Ichikawa I, Ferrone RA, Duchin KL, Manning M, Dzau VJ, BRENNEk BM: Relative contribution of vasopressin and angiotensin II to the altered renal microcirculatory dynamics on two kidney Goldblatt hypertension. Circ Res 53:592–602, 1983
  20. KRakower CA, Greenspon SA: Localization of the nephrotoxic antigen within the isolated renal glomerulus. Arch Pathol 51:629–639, 1951 | ChemPort |
  21. Wilson CB, Dixon FJ, Fortner JG, Cerilli J: Glomerular basement membrane reactive antibody in anti-lymphocyte globulin. J Clin Invest 50:1525–1535, 1971
  22. Blantz RC, Tucker BJ: Measurement of glomerular dynamics, in, Methods in Pharmacology, Renal Pharmacology, edited by Martinez–Maldonado M, New York, Plenum Press, 4B:141–163, 1978
  23. Allison MEM, Wilson CB, Gottschalk CW: Pathophysiology of experimental glomerulonephritis in rats. J Clin Invest 53:1402–1423, 1974 | PubMed | ISI | ChemPort |
  24. Blantz RC, Wilson CB: Acute effects of anti-glomerular basement membrane antibody on the process of glomerular filtration in the rat. J Clin Invest 58:899–911, 1976 | PubMed |
  25. Wilson CB: Immunohistopathology of the kidney, in Manual of Clinical Immunology, (2nd ed), edited by Rose NR, Friedma'n H, Washington, D.C., American Society for Microbiology, pp. 886–894, 1980
  26. Wilson CB, Gushwa LC, Peterson OW, Tucker BJ, Blantz RC: Glomerular immune injury in the rat. The effect of antagonists of histamine activity. Kidney Int 20:628–635, 1981
  27. Blantz RC, Tucker BJ, Gushwa LC, Peterson OW, Wilson CB: Glomerular immune injury in the rat. The influence of All and alpha-adrenergic inhibitors. Kidney Int 20:452ndash;461, 1981 | PubMed | ISI | ChemPort |
  28. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951 | PubMed | ISI | ChemPort |
  29. Dworkin LD, Hostetter TH, Rennke HG, Brenner BM: Hemodynamic basis for glomerular injury in rats with desoxycorticosterone salt hypertension. J Clin Invest 73:1448–1461, 1984 | PubMed | ISI | ChemPort |
  30. Zar JH: Multiple comparisons, in Biostatistical Methods (2nd ed, Chapter 12), Englewood Cliffs, New Jersey, Prentice-Hall, Inc., 1984, pp. 185–205
  31. Dunn O, Clark V: Applied Statistics: Analysis of Variance and Regression. New York, Wiley, 1974
  32. Pelayo JC, Blantz RC: Analysis of renal denervation in the hydropenic rat. Interactions with angiotensin II. Am J Physiol 246:F87–F95, 1984
  33. Blantz RC: Effect of mannitol on glomerular ultrafiltration in the hydropenic rat. J Clin Invest 54:1135–1143, 1974
  34. Brenner BM, Meyer TW, Hostetter TH: Dietary protein intake and the progressive nature of kidney disease: The role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med 307:652–659, 1982 | PubMed | ISI | ChemPort |
  35. Anderson S, Meyer TW, DeGraphenreid RL, Rennke HG, Brenner BM: Control of glomerular hypertension preserves glomerular structure and function in rats with renal ablation. (abstract) Clin Res 32:564A, 1984
  36. Bank N, Alterman L, Aynedjian HS: Selective deep nephron hyperfiltration in uninephrectomized spontaneously hypertensive rats. Kidney Int 24:185–191, 1983
  37. Brenner BM: Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int 23:647–655, 1983 | PubMed | ISI | ChemPort |
  38. Neugarten J, Kaminetsky B, Feiner H, Schacht RG, Liu DT, Baldwin DS: Nephrotoxic serum nephritis with hypertension: Amelioration by antihypertensive therapy. Kidney Int 28:135–139, 1985 | PubMed | ISI | ChemPort |
  39. Okuda S, Onoyama K, Fujimi S, Oh Y, Nomoto K, Omae T: Influence of hypertension on the progression of experimental autologous immune complex nephritis. J Lab Clin Med 101:461–471, 1983 | PubMed | ISI | ChemPort |
  40. Azar S, Keane W, Raij L: Antihypertensive therapy in nephritic spontaneously hypertensive rats: Effects on nephron dynamics and morphology. (abstract) Kidney Int 27:187, 1985

Extra navigation

.
ADVERTISEMENT