Thromboxane mediates the anti-thymocyte antibody and complement
induced impairment of renal hemodynamics in the isolated perfused rat
kidney.
Jocks, Thomas, G. Zahner, U. Helmchen, U. Kneissler, and R. A. K.
Stahl.
Department of Medicine, Division of Nephrology, University of
Hamburg, Germany, Department of Pathology, University of Hamburg,
Germany
APStracts 2:0150F, 1995.
In order to evaluate the possible role of resident glomerular cells in
the formation of thromboxane B2 (Tx) and its hemodynamic consequences
in glomerular immune injury, we studied hemodynamic functions and
glomerular thromboxane formation in a model of the isolated perfused
rat kidney. Glomerular injury was induced in isolated perfused
kidneys by the perfusion with an anti-thymocyte antibody (ATS), which
was followed by rat serum (RS) as complement source. Control kidneys
were either perfused with non-antibody IgG plus RS, RS alone, ATS
plus heat inactivated RS, or ATS alone. Glomerular filtration rate
(GFR), renal vascular resistance (RVR), and renal perfusate flow
(RPF) were assessed over a 80 min period. To study the effect of
immune injury on Tx formation, glomeruli were isolated and TxB2 was
assessed by an enzyme immunoassay. The possible role of Tx on renal
hemodynamics was studied by the pretreatment with a combination of
the Tx synthesis inhibitor UK 38485 and the Tx receptor blocker
Daltroban prior to the perfusions. When rats were perfused with ATS
and RS, GFR fell significantly and was maximally reduced at 10 min
(Control:501 +/- 111, ATS + RS:138 +/- 86 ml/g kidney/min,
significance of F = 0.000) after the application. Similarly RPF (ml/g
kidney/min) fell from 19.2 +/- 1.8 to 6.1 +/- 2.0, (significance of F
= 0.000), whereas RVR (mmHg/ml/g/min) increased threefold from 5.2
+/- 0.4 to 17.9 +/- 5.0 at 10 min after induction of the immune
injury. All these hemodynamic alterations were completely ameliorated
by the pretreatment of the rats with Daltroban and UK 38485. When
erythrocytes were added to the perfusate RVR and GFR increased,
whereas RPF decreased compared with kidneys which were perfused cell
-free only. ATS and RS also induced a decrease in GFR and RPF, an
effect which was abolished by UK 38485 and Daltroban. These
hemodynamic changes appeared without alterations in filtration
fraction. ATS alone, RS alone, and the other combinations had no
effect on renal hemodynamics. Compared to untreated, perfused control
kidneys, glomerular Tx formation (42.4 pg/mg protein/min) was
significantly increased in glomeruli which received ATS and rat serum
(76.9 pg/mg protein/min), whereas glomerular TxB2 formation from rats
which were pretreated with Daltroban and UK 38485 was significantly
reduced (27.2 pg/mg protein/min). These data demonstrate that
glomerular resident cells participate to a large extent in the
formation of thromboxane in kidneys with immune mediated glomerular
injury and play an important role in the mediation of glomerular
hemodynamics in this experimental injury.
Received 6 December 1994; accepted in final form 9 August 1995.
APS Manuscript Number F432-4.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 15 September 1995.