Role for local prostaglandin and thromboxane production in the regulation of glomerular filtration rate in the rat with streptozocin-induced diabetes.
We examined the relationship between glomerular filtration rate (GFR), as assessed by inulin clearance, and glomerular prostaglandin and thromboxane production as a function of glycemic control in control rats and rats that had had streptozocin-induced diabetes for 2 months. In severely hyperglycemic (plasma glucose level 644 +/- 40 mg/dl) rats with streptozocin-induced diabetes that had not been treated with insulin, GFR was reduced to values below those in control rats by 2 months, whether data were expressed as milliliters per minute or as a function of kidney weight. By contrast, treatment of the diabetic rats with insulin to maintain moderate hyperglycemia (plasma glucose concentration 398 +/- 40 mg/dl) resulted in a persistent elevation of GFR compared with values in control rats. Basal production of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolic product of prostaglandin I2 (PGl2), by glomeruli isolated from the moderately hyperglycemic rats was higher than corresponding values of glomeruli from control rats. Differences in PGE2 and 6-keto-PGF1 alpha production by glomeruli from moderately hyperglycemic and control rats were abolished by addition of arachidonate to the incubation mixture, supporting a role for enhanced availability of arachidonate in the mediation of altered vasodilatory prostaglandin production. By contrast, glomerular production of thromboxane B2 (TXB2), the stable metabolic product of thromboxane A2 (TXA2), was not different in moderately hyperglycemic rats compared with controls. Thus, enhanced production of vasodilatory prostaglandins by glomeruli from moderately hyperglycemic rats was associated with an increase in GFR.(ABSTRACT TRUNCATED AT 250 WORDS)
Craven
P A
PA
Department of Medicine, Veterans Administration Medical Center, Pittsburgh, PA 15240.
DeRubertis
F R
FR
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000628:therapy; D015232:Dinoprostone / Q000032:analysis; D005260:Female; D005919:Glomerular Filtration Rate; D007328:Insulin / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000378:metabolism / Q000503:physiopathology*; D009929:Organ Size; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D013929:Thromboxane B2 / Q000032:analysis; D013931:Thromboxanes / Q000096:biosynthesis / Q000502:physiology*
D001786:Blood Glucose; D007328:Insulin; D011453:Prostaglandins; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013311:Streptozocin; D015232:Dinoprostone