Faculty Collaboration Database

Mesangial cell immune injury: effects of thromboxane receptor antagonism. J Am Soc Nephrol 1991 Feb;1(8):1041-7

Date

02/01/1991

Pubmed ID

1832980

DOI

10.1681/ASN.V181041

Scopus ID

2-s2.0-0026110985 (requires institutional sign-in at Scopus site)   3 Citations

Abstract

We assessed the renal hemodynamic changes occurring acutely after glomerular mesangial cell immune injury and the effects of thromboxane receptor antagonism on these changes. A single intravenous proteinuric dose of a monoclonal antibody raised against the rat thymocyte antigen Thy 1.1 (ER4), which is also expressed in rat mesangial cells, induced acute decrements in glomerular filtration rate and in renal blood flow in male Munich-Wistar rats. One hour after administration of 4 to 6 mg/kg of ER4 antibody, glomerular filtration rate and renal blood flow decreased by 80 and 36%, respectively. These decrements were associated with significant increments in basal thromboxane B2 synthesis in isolated glomeruli and no changes in glomerular prostaglandin E2 synthesis. Pretreatment of animals with the thromboxane receptor antagonist SQ-29,548 (2 mg/kg) significantly ameliorated decrements in glomerular filtration rate and renal blood flow. Pretreatment with a structurally dissimilar thromboxane receptor antagonist, L-670,596 (3 mg/kg) had no effect. Both antagonists at the doses employed abolished the decrements in renal blood flow induced by systemic administration of the thromboxane mimetic U-46619. Whereas the SQ-29,548 antagonist had no effect on glomerular leukotriene B4 and 12-hydroxyeicosatetraenoic acid synthesis, the L-670,596 thromboxane receptor antagonist significantly inhibited glomerular synthesis of these eicosanoids in immunologically injured glomeruli. These observations indicate that in mesangial cell immune injury the protective effect of thromboxane A2 receptor antagonism on glomerular filtration rate and renal blood flow is not solely due to inhibition of the vasoconstrictor effects of thromboxane A2. An effect on the synthesis of arachidonate lipoxygenation products may also play a role.

Author List

Bresnahan BA, Roman RJ, Bagchus WM, Lianos EA

Author

Barbara A. Bresnahan MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Animals
Antilymphocyte Serum
Bridged Bicyclo Compounds, Heterocyclic
Carbazoles
Eicosanoids
Fatty Acids, Unsaturated
Glomerular Filtration Rate
Glomerular Mesangium
Hydrazines
Male
Prostaglandin Endoperoxides, Synthetic
Rats
Rats, Inbred Strains
Receptors, Prostaglandin
Receptors, Thromboxane
Thromboxane A2