Effects of angiotensin II blockade on nitric oxide blood levels in IgA nephropathy.
BACKGROUND
The effects of renin-angiotensin system blockade on nitric oxide (NO), especially in pathological conditions, are far from being established. The influence of kinins and angiotensin type 2 receptor are largely speculative and based mainly on animal studies. This study was aimed to address these aspects in humans.


METHODS
Eight IgA nephropathy patients with documented clinical and histological indicators of poor prognosis were given 50 mg of losartan, 10 mg of enalapril, and 40 mg of the NO donor isosorbide 5 mononitrate (as a control of NO generation) in randomized order for 7 days each. Treatment periods were separated by washout periods of 7 days each. Laboratory investigations were performed before and after each study period. Seven healthy controls received losartan and enalapril according to the same study design.


RESULTS
Glomerular filtration rate remained stable while effective renal plasma flow increased with each treatment (P<0.05). Under losartan and enalapril, filtration fraction fell (P=0.02), plasma renin activity increased (P<0.05) and urinary aldosterone concentration decreased (P=0.02). Angiotensin-converting enzyme activity was reduced to the limit of detection under enalapril (P<0.001). Blood NO, detected as nitrosylhaemoglobin by a recently developed technique of spin-trap electron paramagnetic resonance, increased significantly, as expected, during treatment with isosorbide 5 mononitrate (P=0.01), with enalapril (P<0.05), and also with losartan (P<0.05). Unlike losartan, enalapril significantly reduced albuminuria (P=0.01) in this short-term period. In the seven healthy controls, neither enalapril nor losartan were able to increase blood NO levels significantly.


CONCLUSIONS
Blood levels of nitrosylhaemoglobin, a surrogate marker of NO, increased under blockade of the renin-angiotensin system in patients with IgA nephropathy, but not in healthy volunteers. This increase could contribute to changes of effective renal plasma flow in renal disease states.
Roccatello
D
D
Centro di Immunopatologia (CMID), Ospedale L. Einaudi, Torino, Italy.
Mengozzi
G
G
Gigliola
G
G
Rossi
D
D
Mosso
R
R
Cacace
G
G
Polloni
R
R
Cesano
G
G
Picciotto
G
G
Paradisi
L
L
Bancale
E
E
Piccoli
G
G
Sena
L M
LM
D000328:Adult; D000368:Aged; D000419:Albuminuria; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000627:therapeutic use; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D020030:Nitric Oxide Donors / Q000627:therapeutic use; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D006454:Hemoglobins; D020030:Nitric Oxide Donors; C008657:nitrosyl hemoglobin; D000804:Angiotensin II; D009569:Nitric Oxide; D004656:Enalapril; D007548:Isosorbide Dinitrate; D019808:Losartan; C030397:isosorbide-5-mononitrate