High-protein feeding stimulates renal thromboxane production in rats with streptozocin-induced diabetes.
In diabetic rats glomerular morphologic damage is exacerbated by feeding a protein-rich diet. Protein feeding alters arachidonic acid metabolism in other models of renal disease, and there is evidence that the arachidonic acid metabolite thromboxane plays a pathophysiologic role in protein-induced renal injury. In this study we evaluated the effect of high-protein feeding on renal thromboxane production, renal hemodynamics, and renal morphologic condition in rats with experimentally induced diabetes. We induced diabetes in male Sprague-Dawley rats by streptozocin administration. Rats then received high (60% casein)- or low (8% casein)-protein diets. Eight to 11 weeks later, clearance of inulin and PAH and renal blood flow were measured. Rats fed 60% casein had higher glomerular filtration rate and renal blood flow than rats fed low-protein diets. Rats fed high-protein diets had more glomerular hypercellularity, tubular hypertrophy, and arteriolar thickening than their protein-restricted counterparts. Renal production of 6-keto-PGF1a and PGE2 was not different between dietary groups. Renal thromboxane production, however, was greater in rats fed 60% protein than in rats fed 8% protein. We conclude that protein feeding stimulates renal thromboxane production and exacerbates morphologic injury in the diabetic rat. Short-term administration of the thromboxane synthetase-inhibitor UK 38,485 did not further increase glomerular filtration rate or renal blood flow in animals fed high protein. Thus thromboxane did not appear to play a role in protein-induced injury in this model by a vasoconstrictive mechanism. Other possible mechanisms by which thromboxane may contribute to the renal damage observed are discussed.
Collins
D M
DM
Duke University Medical Centers, Durham, N.C.
Coffman
T M
TM
Ruiz
P
P
Klotman
P E
PE
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000096:biosynthesis*
D004044:Dietary Proteins; D011453:Prostaglandins; D013931:Thromboxanes; D013930:Thromboxane-A Synthase