Chronic inhibition of nitric oxide synthase in Heymann nephritis.
Effects of nitric oxide (NO) synthase inhibition on blood pressure and on the course of Heymann nephritis was examined in rats. L-NG-nitroarginine-methylester (L-NAME, 10 mg/100 ml in the drinking water for 12 weeks) was used as an inhibitor of NO synthase. Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of NO, was used as an indirect estimate of NO activity. Rats were divided into the following groups: control, nephritis, L-NAME, and nephritis-L-NAME. Urinary cGMP excretion was lower in the nephritis group (p < 0.05) and in the nephritis-L-NAME group (p < 0.005) compared with controls. Plasma atrial natriuretic peptide (ANP) levels were elevated in the nephritis (p < 0.001) and in the nephritis-L-NAME groups (p < 0.05. L-NAME treatment alone did not have any effect on plasma ANP levels. Blood pressure rose progressively in all L-NAME-treated rats. Most marked albuminuria developed in the nephritis-L-NAME group. No differences in the immunohistological findings were observed between the nephritis and the nephritis-L-NAME groups. NO synthase inhibition causes hypertension and aggravates albuminuria in chronic nephritis. Moreover, nephritis itself may decrease then production of cGMP either as a consequence of blunted NO activity or, in addition, because of ANP resistance. It appears that NO synthase inhibition does not change the immunological course of Heymann nephritis but rather the increased hemodynamic load makes the course of nephritis worse.
Uhlenius
N
N
Minerva Foundation Institute for Medical Research, Finland.
Tikkanen
I
I
Tikkanen
T
T
Miettinen
A
A
Törnroth
T
T
Fyhrquist
F
F
D000419:Albuminuria; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001327:Autoimmune Diseases / Q000139:chemically induced; D001794:Blood Pressure; D003176:Complement C3 / Q000032:analysis; D006152:Cyclic GMP / Q000652:urine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000737:chemistry / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000097:blood; D013997:Time Factors
D003176:Complement C3; D004791:Enzyme Inhibitors; D007074:Immunoglobulin G; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D019001:Nitric Oxide Synthase; D012083:Renin; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester