Restoration of glomerular haemodynamics and renal injury independent of arterial hypertension in rats with subtotal renal ablation.
To study whether prevention of renal injury using the anti-inflammatory drugs pentosan polysulphate (PPS) and mycophenolate mofetil (MMF) is associated with improvement of glomerular haemodynamics, PPS and MMF were compared with losartan. The awake systolic blood pressure (SBP), proteinuria (Uprot) and micropuncture studies were performed 30 days after five-sixths nephrectomy in untreated rats and in rats treated with PPS (100 mg/kg per day), MMF (30 mg/kg per day) or losartan (30 mg/kg per day). In the rats receiving no treatment, there was a rise in SBP (to 180-200 mmHg) and in Uprot, which were prevented by losartan. In the PPS and MMF groups, the SBP was elevated but the Uprot did not increase. In the untreated rats the total glomerular filtration rate (GFR) decreased (-80%) and the single-nephron GFR (37-42%), plasma flow (67-127%) and glomerular pressure (10-15 mmHg) increased. These changes were prevented by PPS and MMF to the same extent as by losartan: the rise in single-nephron GFR and plasma flow were reduced by 50% and the glomerular pressure was normal. In rats receiving losartan, this was due to the fall in arterial pressure, whereas in PPS- and MMF-treated rats it was due to a rise in afferent resistance, indicating autoregulatory capacity. Total GFR was similar, despite the lower single-nephron GFR in treated groups, suggesting a larger proportion of functioning nephrons. Losartan, PPS and MMF significantly reduced glomerular sclerosis and tubular dilation and atrophy in association with a reduction in the lymphocyte and macrophage infiltrate. These results suggest an interaction between the haemodynamic and inflammatory changes that perpetuate each other during progression of renal injury. Renal protection provided by anti-inflammatory drugs is partially mediated by the prevention of glomerular haemodynamic alterations.
Instituto Nacional de Cardiología, Departamento de Nefrología, Juan Badiano 1-Tlapan 1, D.F. 4080-1408 Mexico, D.F., México. jherrera@rtn.net.mx
Jaime
J
Herrera-Acosta
Edilia
E
Tapia
Laura G
LG
Sánchez-Lozada
Martha
M
Franco
Liliane J
LJ
Striker
Gary E
GE
Striker
Iturbe Bernardo
IB
Rodríguez
D000818:Animals; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009392:Nephrectomy; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology; D051381:Rats; D013599:Systole
D010426:Pentosan Sulfuric Polyester; D009173:Mycophenolic Acid