ISSN:
1432-0428
Keywords:
Keywords Diabetic nephropathy
;
renal microcirculation
;
aldose reductase
;
tolrestat
;
galactose-feeding
;
isolated perfused kidney.
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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 180 mm 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. [Diabetologia (1996) 39: 907–914]
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00403909
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