L-Arginine improves endothelial function in renal artery of hypertensive Dahl rats.
OBJECTIVE
To clarify whether endothelium-derived contracting factor (EDCF) is developed in renal artery of hypertensive Dahl rats and whether prolonged oral L-arginine treatments prevent development of EDCF and hypertension.


METHODS
The effect of prolonged salt treatment with or without L-arginine on the renal artery was examined.


RESULTS
Dahl salt-sensitive and -resistant rats were fed a 0.4 or an 8% NaCl diet for 4 weeks. High sodium intake increased arterial pressure in Dahl salt-sensitive rats. The rings of renal arteries were suspended for isometric tension recording. Only in the hypertensive rats, more than 1 micromol/l acetylcholine induced an endothelium-dependent contraction response. The contraction was completely inhibited by indomethacin or ONO-3708 [prostaglandin H2 (PGH2)/thromboxane A2 (TXA2) receptor antagonist], and partially inhibited by OKY-046 (TXA2 synthetase inhibitor). Acetylcholine-induced relaxation was significantly depressed in hypertensive rats, which was partially improved by SQ29548 (PGH2/TXA2 receptor antagonist). Oral L-arginine, but not ONO-8809 (orally active PGH2/TXA2 receptor antagonist) treatment, inhibited the contraction and amended the relaxation. The endothelium-independent contraction to TXA2 receptor agonist U46619 and relaxation to nitroprusside were not altered by L-arginine treatment The L-Arginine treatment reduced blood pressure and sodium retention with increases in urinary NO2-/NO3- and cGMP excretion. Hydralazine treatment also inhibited development of EDCF.


CONCLUSIONS
The present results suggest that impaired endothelium-dependent relaxation to acetylcholine is caused in part by induction of EDCF synthesis/release in renal arteries of hypertensive Dahl rats. L-arginine can attenuate sodium retention and development of hypertension, which lead to a decrease in EDCF synthesis in renal arteries.
Zhou
M S
MS
The Second Department of Physiology, Kagawa Medical University, Japan.
Kosaka
H
H
Tian
R X
RX
Abe
Y
Y
Chen
Q H
QH
Yoneyama
H
H
Yamamoto
A
A
Zhang
L
L
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D006152:Cyclic GMP / Q000652:urine; D016232:Endothelins / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D005231:Fatty Acids, Unsaturated; D006830:Hydralazine / Q000494:pharmacology; D006834:Hydrazines; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D020303:Rats, Inbred Dahl; D012077:Renal Artery / Q000187:drug effects* / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016232:Endothelins; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D008689:Methacrylates; D009566:Nitrates; D009573:Nitrites; D009599:Nitroprusside; D006830:Hydralazine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; C049855:ONO 3708; D001120:Arginine; D006152:Cyclic GMP; C034364:ozagrel; D000109:Acetylcholine; D007213:Indomethacin