thromboxane-a2 and Nephritis

Because of their vasodilator and vasoconstrictor properties, vasoactive prostaglandins and thromboxane A2 have been proposed as modulators of the hemodynamic changes that occur in experimental models of renal disease. Increased synthesis of vasodilatory prostaglandins (PGE2) and perhaps prostaglandin I2 (PGI2) play a role in the maintenance of renal blood flow and GFR during states of impaired perfusion. In contrast, thromboxane A2 has been implicated as the vasoconstrictor responsible for the reduction of renal blood flow and GFR in certain animal models of experimental renal disease. These products and other metabolites of arachidonic acid may also participate in the immunological events underlying the onset and/or progression of experimental renal disease. It is evident that the pathophysiologic role of eicosanoids in experimental renal disease is not fully understood. Additional studies and further understanding of the many other potential roles of eicosanoids on immunological events, hemodynamic states, mesangial cell physiology, etc. are needed to comprehend more fully the extent of the participation of eicosanoids in the pathogenesis and pathophysiology of renal disease.

Topics: Animals; Dietary Fats; Eicosanoids; Glomerulonephritis; Hypertension; Kidney Diseases; Nephritis; Prostaglandins; Rabbits; Rats; Thromboxane A2; Ureteral Obstruction

To study the changes and roles of plasma thromboxane A2 (TXA2) and prostaglandin I2 (PGT2) levels and their ratio in Henoch-Schonlein purpura nephritis (HSPN) in children.. Plasma levels of TXA2 and PGI2 were measured using ELISA in 45 children with HSPN and 20 healthy children.. Plasma TXA2 level was significantly higher, while plasma PGI2 level was significantly lower in HSPN children in the acute phase than in the control (P<0.01). The ratio of TXA2/PGI2 in HSPN children in the acute phase was statistically higher than in the control (9.55+/-3.56 vs 0.87+/-0.21; P<0.01). In the convalescence phase, plasma TXA2 level remained higher and plasma PGI2 level was elevated and higher than in the control, so the ratio of TXA2/PGI2 was reduced to normal level.. The imbalance of TXA2 and PGI2 may be involved in the development of renal damage in children with HSPN. The balance of TXA2 and PGI2 contributes to renal recovery.

Topics: Adolescent; Child; Child, Preschool; Epoprostenol; Female; Humans; IgA Vasculitis; Male; Nephritis; Thromboxane A2

Recently, it has been demonstrated that the production of prostaglandins and thromboxane is increased in patients with chronic glomerulonephritis and lupus nephritis. We recently demonstrated that thromboxane A(2) delayed the clearance of heat-aggregated bovine serum albumin deposited in glomeruli. In the present study, we investigated the effect of thromboxane A(2) on the clearance of macromolecules in nephritic glomeruli. First, we attempted to clarify the conditions for the clearance of heat-aggregated bovine serum albumin in nephritic glomeruli, using glomeruli isolated from control and anti-glomerular basement membrane nephritic mice. Heat-aggregated bovine serum albumin was injected twice into each mouse. The glomeruli were then isolated and incubated in culture medium. The heat-aggregated bovine serum albumin content of control glomeruli gradually diminished with incubation time up to 24 h. The heat-aggregated bovine serum albumin content of nephritic glomeruli was 69% higher than that of control glomeruli at 24 h incubation. The production of thromboxane B(2) (the stable metabolite of thromboxane A(2)) in nephritic glomeruli showed about a sevenfold increase compared with control. DP-1904 [6-(1-imidazolylmethyl)-5,6,7,8-tetrahydro-naphthalene-2-carboxylic acid hydrochloride], a thromboxane A(2) synthase inhibitor, and KT2-962 [sodium 3-(4-(4-chlorophenyl-butylsulfonamido) butyl)-6-isopropylazulene-1-sulfonate], a selective thromboxane A(2) receptor antagonist, significantly reduced the heat-aggregated bovine serum albumin content in nephritic glomeruli. Normal glomeruli treated with U-46619 [15S-hydroxy-11a,9a-(epoxymethano)prosta-5Z,13E-dienoic acid], a stable analogue of thromboxane A(2), had significantly more heat-aggregated bovine serum albumin than control glomeruli. We next investigated whether thromboxane A(2) could affect the uptake/disposal of heat-aggregated bovine serum albumin by cultured rat mesangial cells. U-46619 significantly enhanced the uptake and inhibited the disposal of heat-aggregated bovine serum albumin by mesangial cells. Finally, we performed experiments to elucidate the role of the thromboxane A(2) receptor (TP receptor) in the clearance of heat-aggregated bovine serum albumin using TP-deficient mice. The glomerular heat-aggregated bovine serum albumin content of TP-receptor knockout [TP(-/-)] mice was lower than that of wild-type [WT(+/+)] mice. U-46619 dose dependently increased the uptake of heat-aggregated bovine s

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Antibodies; Autoantibodies; Benzenesulfonates; Cells, Cultured; Cycloheptanes; Enzyme Inhibitors; Glomerular Mesangium; Hot Temperature; Imidazoles; Kidney Glomerulus; Lupus Nephritis; Male; Mice; Mice, Inbred ICR; Mice, Knockout; Nephritis; Receptors, Thromboxane; Serum Albumin, Bovine; Tetrahydronaphthalenes; Thromboxane A2; Thromboxane-A Synthase; Vasoconstrictor Agents

To clarify the role of thromboxane A2 (TxA2), endothelin-1 (ET-1) and endothelin-3 (ET-3) in the progression of glomerular injury in accelerated nephrotoxic serum nephritis (NTN) in the rat, we studied the expression of ET-1 and ET-3 at the kidney by immunohistochemical method and examined the effect of a novel TxA2 receptor antagonist, S-1452. The S-1452-treated group showed significantly lowered 24-hr proteinuria and milder glomerular cell proliferation and lobulation than the non-treated group (NT group) on experimental day 10. There was no significant difference in the glomerular polymorphonuclear cell (PMN) exudation between the 2 groups. Immunofluorescent findings revealed that ET-1 and ET-3 were seen along the glomerular capillary wall and partly in the mesangial area in all rats of the NTN group. The degree and positive rate of ET-1 and ET-3 staining were significantly higher in the NTN group than in the S-1452 group. These findings suggest that TxA2 may be an important mediator in the development of NTN, and that TxA2 receptor antagonist may be useful for the reduction of glomerular injury in this type of nephritis. In addition, local production of ET may contribute to the development of this nephritis.

Topics: Animals; Bridged Bicyclo Compounds; Chromium; Endothelin-1; Endothelin-3; Fatty Acids, Monounsaturated; Immunohistochemistry; Kidney Glomerulus; Male; Microscopy, Fluorescence; Nephritis; Prostaglandin Antagonists; Proteinuria; Rabbits; Rats; Rats, Wistar; Receptors, Thromboxane; Sodium; Thromboxane A2

Late heterologous and autologous stages of serum nephritis together with glomerular cells in culture are studied biochemically, morphologically and immunohistochemically for the assessment of the role of mononuclear leucocyte mediator system. The heterologous stage of the nephrotoxic nephritis is associated with the increase of Interleukin-I and TxA2 production. Role of Interleukin-I in the autologous stage is less pronounced in spite of proliferative activity of cultured mesangial cells. The effect of suppressive factors prevails in the glomerulus.

Topics: Animals; Cell Division; Immunohistochemistry; Interleukin-1; Male; Nephritis; Rats; Rats, Inbred Strains; Thromboxane A2