Impairment of afferent arteriolar myogenic responsiveness in the galactose-fed rat.
Previous studies from our laboratory have demonstrated impaired afferent arteriolar responsiveness to pressure in rats 4-6 weeks after the induction of diabetes mellitus. Although the responsible mechanisms mediating this renal autoregulatory defect have not been fully defined, increased polyol metabolism has been implicated as a possible factor involved in the pathogenesis of diabetic complications. We therefore investigated the possible role of this metabolic disturbance in renal autoregulation using the galactose-fed rat, a model characterized by increased polyol pathway activity independent of hyperglycemia or insulin deficiency. Hydronephrosis was induced to permit direct visualization of renal microvessels. Pressure-induced vasoconstriction of afferent arterioles was assessed by quantitating vessel diameter following stepwise increments of renal perfusion pressure (RAP; from 80 to 180 mm Hg) in the hydronephrotic kidneys from control rats and rats fed a 50% galactose diet for 2 or 4 weeks. Vessel diameters were measured from video images by computer-assisted image processing. Control rats exhibited progressive afferent arteriolar vasoconstriction when RAP was increased from 80 to 180 mm Hg (-17.3% +/- 1.0%; P < 0.001). In contrast, myogenic responses to increases in pressure were absent in the afferent arterioles of rats fed a 50% galactose diet for either 2 (-4.1% +/- 1.9%; not significant) or 4 weeks (-2.9 +/- 3.4%; not significant). Our demonstration that the impairment of afferent arteriolar responsiveness to increasing RAP in the normoglycemic galactose-fed rat was identical to that observed in the STZ-diabetic rat suggests that increased polyol accumulation may contribute to the impairment of renal autoregulation in the diabetic rat.
Forster
H G
HG
Nephrology Section, Department of Veterans Affairs Medical Center, Miami, Florida 33125.
ter Wee
P M
PM
Takenaka
T
T
Hohman
T C
TC
Epstein
M
M
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure; D016861:Cyclooxygenase Inhibitors; D003921:Diabetes Mellitus, Experimental; D004032:Diet; D004195:Disease Models, Animal; D004376:Galactitol / Q000378:metabolism; D005690:Galactose / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006706:Homeostasis; D006869:Hydronephrosis; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D008297:Male; D010477:Perfusion; D011108:Polymers / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D011108:Polymers; C024617:polyol; D004376:Galactitol; D007052:Ibuprofen; D005690:Galactose