High-protein feeding stimulates renal thromboxane production in rats with streptozocin-induced diabetes

J Lab Clin Med. 1989 Nov;114(5):545-53.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dietary Proteins / administration & dosage
  • Dietary Proteins / pharmacology*
  • Hemodynamics / drug effects
  • Kidney / blood supply
  • Kidney / metabolism*
  • Kidney / pathology
  • Male
  • Prostaglandins / biosynthesis
  • Rats
  • Rats, Inbred Strains
  • Thromboxane-A Synthase / antagonists & inhibitors
  • Thromboxanes / biosynthesis*


  • Dietary Proteins
  • Prostaglandins
  • Thromboxanes
  • Thromboxane-A Synthase