Inhibition of nitric oxide activity by arginine analogs in human renal arteries.
BACKGROUND
Plasma levels of endogenous guanidine compounds are increased in various pathologic conditions, including chronic renal failure. In the present study we tested the effects of some of these compounds on basal and stimulated nitric oxide activity in human renal arteries.


METHODS
Rings from human renal arteries were obtained from 22 patients undergoing nephrectomy. The rings were suspended in organ baths for isometric recording of tension. We then studied the effects of N(G)-monomethyl-L-arginine (L-NMMA), N(G),N(G)-dimethyl-L-arginine (asymmetrical dimethylarginine [ADMA]), aminoguanidine (AG), and methylguanidine (MG) on artery rings under basal and stimulated conditions.


RESULTS
In precontracted arteries, L-NMMA (1 micromol/L to 1 mmol/L) and ADMA (1 micromol/L to 3 mmol/L) caused concentration- and endothelium-dependent contractions (median effective concentrations [EC50] = 13.3 micromol/L and 17.5 micromol/L, respectively; Emax = 15+/-4% and 17+/-4% of the response to 100 mmol/L KCl, respectively). Aminoguanidine (0.01 to 3 mmol/L) and MG (0.01 to 3 mmol/L) produced endothelium-independent contractions (Emax = 9+/-3% and 16+/-2% of the response to 100 mmol/L KCl, respectively). L-arginine (1 mmol/L) but not D-arginine (1 mmol/L) prevented the contractions by L-NMMA and ADMA, but did not change contractions induced by AG and MG. In precontracted arteries, the relaxation to acetylcholine was decreased but not abolished by L-NMMA and ADMA. The remaining relaxation was reduced by charybdotoxin (0.1 mol/L) and tetraethylammonium (1 mmol/L).


CONCLUSIONS
The results demonstrate that L-NMMA and ADMA reduce basal and stimulated nitric oxide activity in human renal arteries. An increase in the plasma concentrations of methylarginines associated with renal disease should be considered as a risk factor for endothelial dysfunction and abnormal vasomotor tone in human renal arteries.
Segarra
G
G
Department of Fisiología, Universidad de Valencia, Spain.
Medina
P
P
Vila
J M
JM
Chuan
P
P
Domenech
C
C
Torondel
B
B
Lluch
A
A
D000109:Acetylcholine / Q000378:metabolism; D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D012077:Renal Artery / Q000378:metabolism*; D012307:Risk Factors
D015415:Biomarkers; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine