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

Impairment of afferent arteriolar myogenic responsiveness in the galactose-fed rat is prevented... 125 39 39 8 8 H. G. Forster P. M. ter Wee T. C. Hohman M. Epstein Nephrology Section, Department of Veterans Affairs Medical Center and Division of Nephrology University of Miami School of Medicine Miami Florida USA Wyeth-Ayerst Research Princeton New Jersey USA 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Diabetologia Springer Journals

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

Diabetologia, Volume 39 (8) – Aug 1, 1996

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Publisher
Springer Journals
Copyright
Copyright © 1996 by Springer-Verlag
Subject
Medicine & Public Health; Internal Medicine; Metabolic Diseases; Human Physiology
ISSN
0012-186X
eISSN
1432-0428
DOI
10.1007/BF00403909
Publisher site
See Article on Publisher Site

Abstract

125 39 39 8 8 H. G. Forster P. M. ter Wee T. C. Hohman M. Epstein Nephrology Section, Department of Veterans Affairs Medical Center and Division of Nephrology University of Miami School of Medicine Miami Florida USA Wyeth-Ayerst Research Princeton New Jersey USA 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.

Journal

DiabetologiaSpringer Journals

Published: Aug 1, 1996

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