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Impairment of afferent arteriolar myogenic responsiveness in the galactose-fed rat is prevented by tolrestat

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Summary

By permitting the separation of increased aldose reductase activity from hyperglycaemia and insulin deficiency, galactose-fed rats have constituted a useful model for investigating diabetic complications. Such rats manifest an impaired afferent arteriolar responsiveness to pressure similar to that of rats 4 to 6 weeks after induction of diabetes with streptozotocin. In the present study, we investigated whether treatment of galactose-fed rats with the aldose reductase inhibitor tolrestat prevents this autoregulatory defect and whether the blunted afferent arteriolar responsiveness to pressure is associated with impaired responsiveness to angiotensin II. Pressure-induced vasoconstriction of afferent arterioles was assessed in kidneys made hydronephrotic to allow direct visualization of renal microvessels by computer-assisted image processing. Vessel diameters were quantitated following stepwise increments of renal perfusion pressure (RAP; from 80 to 180 mm Hg) in kidneys of control rats and rats fed a diet for 2 weeks with 50% galactose with or without tolrestat. Subsequent to the pressure studies, angiotensin II (0.3 nmol/l) was added to the perfusate, and vessel diameters were reassessed. Control rats exhibited progressive afferent arteriolar vasoconstriction when RAP was increased from 80 to 180mm Hg (−17.2±1.0%; p<0.001). In contrast, myogenic responses to increases in pressure were absent in the arterioles of the galactose-fed rats (−4.1±1.9%; N.S.). Treatment with tolrestat completely prevented this impairment in afferent arteriolar responsiveness (−16.5±1.8%; p<0.001). The angiotensin II-induced vasoconstriction did not differ between control rats and galactose-fed rats. We conclude that increased aldose reductase activity contributes to impaired renal autoregulation in galactose-fed rats, a model of diabetic nephropathy, but is not involved in the loss of afferent arteriolar responsiveness to angiotensin II.

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Abbreviations

STZ:

Streptozotocin

GFR:

Glomerular filtration rate

RAP:

renal artery pressure

AR:

aldose reductase

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Authors and Affiliations

  1. Nephrology Section, Department of Veterans Affairs Medical Center and Division of Nephrology, University of Miami School of Medicine, Miami, Florida, USA

    H. G. Forster, P. M. ter Wee & M. Epstein

  2. Wyeth-Ayerst Research, Princeton, New Jersey, USA

    T. C. Hohman

Authors
  1. H. G. Forster
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  2. P. M. ter Wee
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  3. T. C. Hohman
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  4. M. Epstein
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Forster, H.G., ter Wee, P.M., Hohman, T.C. et al. Impairment of afferent arteriolar myogenic responsiveness in the galactose-fed rat is prevented by tolrestat. Diabetologia 39, 907–914 (1996). https://doi.org/10.1007/BF00403909

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  • DOI: https://doi.org/10.1007/BF00403909

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