Consequences of acute nitric oxide synthesis inhibition in experimental glomerulonephritis.
To assess the functional relevance of the enhanced glomerular nitric oxide (NO) synthesis during acute nephrotoxic serum (NTS) nephritis, a NO synthesis inhibitor (NOI) NG-monomethyl-L-arginine was administered to normal (N + NOI) and acutely nephritic (NTS + NOI) Munich-Wistar rats, and systemic and glomerular hemodynamic responses were contrasted with those observed in vehicle-treated normal and nephritic (NTS) controls. Urinary protein excretion rates were equal in normal and N + NOI rats but were markedly elevated in NTS animals and further increased in NTS+NOI. NO inhibition in normal animals (normal versus N + NOI) led to reductions in glomerular plasma flow rate and the glomerular capillary ultrafiltration coefficient (Kf) and elevations in afferent and efferent arteriolar resistances and net transcapillary hydraulic pressure difference (delta P), as well as an increase in systemic arterial pressure. The increase in delta P offset the falls in glomerular plasma flow rate and Kf, and GFR was preserved. Directionally similar responses in efferent resistance occurred in NTS + NOI compared with NTS, however, afferent resistance was not further affected by NOI. Additionally, although Kf was severely depressed in the NTS group (approximately 60% versus normal), it was not further depressed by NOI treatment. Polymorphonuclear cell (PMN) infiltration/glomerulus was mildly increased in N + NOI over normal. In contrast, PMN number in NTS + NOI rats was diminished as compared with NTS.(ABSTRACT TRUNCATED AT 250 WORDS)
Ferrario
R
R
Farmitalia Carlo Erba-Biotechnology, Nerviano, Italy.
Takahashi
K
K
Fogo
A
A
Badr
K F
KF
Munger
K A
KA
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009504:Neutrophils / Q000473:pathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D011507:Proteinuria / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000502:physiology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine