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Impairment of afferent arteriolar myogenic responsiveness in the galactose-fed rat is prevented by tolrestat.
- Source :
-
Diabetologia [Diabetologia] 1996 Aug; Vol. 39 (8), pp. 907-14. - Publication Year :
- 1996
-
Abstract
- 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 prevent 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 auto-regulation in galactose-fed rats, a model of diabetic nephropathy, but is not involved in the loss of afferent arteriolar responsiveness to angiotensin II.
- Subjects :
- Angiotensin II pharmacology
Animals
Arterioles drug effects
Arterioles physiology
Blood Pressure drug effects
Blood Pressure physiology
Cohort Studies
Diabetes Mellitus, Experimental physiopathology
Diet
Disease Models, Animal
Enzyme Inhibitors therapeutic use
Galactitol metabolism
Galactose administration & dosage
Image Processing, Computer-Assisted
In Vitro Techniques
Kidney drug effects
Kidney physiology
Male
Muscle, Smooth, Vascular drug effects
Naphthalenes therapeutic use
Perfusion
Rats
Rats, Sprague-Dawley
Vasoconstriction drug effects
Vasoconstrictor Agents pharmacology
Aldehyde Reductase antagonists & inhibitors
Diabetic Nephropathies prevention & control
Enzyme Inhibitors pharmacology
Kidney blood supply
Muscle, Smooth, Vascular physiology
Naphthalenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0012-186X
- Volume :
- 39
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Diabetologia
- Publication Type :
- Academic Journal
- Accession number :
- 8858212
- Full Text :
- https://doi.org/10.1007/BF00403909