Long-term Administration of L-Arginine Improves Nitric Oxide Release From Kidney in Deoxycorticosterone Acetate-Salt Hypertensive Rats

Hayakawa, Hiroshi
Hirata, Yasunobu
Suzuki, Etsu
Kimura, Kenjiro
Kikuchi, Kazuya
Nagano, Tetsuo
Hirobe, Masaaki
Omata, Masao

Second Department of Internal Medicine, Faculty of Medicine (H.H., Y.H., E.S., K. Kimura, M.O.) and the Faculty of Pharmaceutical Sciences (K. Kikuchi, T.N., M.H.), University of Tokyo (Japan).

Correspondence to Yasunobu Hirata, MD, The Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. Previously published in abstract form (Hypertension. 1993; 22:412).

Received February 14, 1994; accepted in revised form March 2, 1994.

Hypertension 23(6):p 752-756, June 1994.

To examine the effects of L-arginine (L-Arg) on endothelial function, we administered 0.5 g/L L-Arg in drinking water to deoxycorticosterone acetate (DOCA)-salt rats for 8 weeks and then measured nitric oxide (NO) release from isolated kidneys using a newly developed real-time chemiluminescence method. Renal pathology was also analyzed. Acetylcholine caused much smaller declines in renal perfusion pressure (10⁻⁷ mol/L acetylcholine: −24±2% [SEM] versus −50±2%, P<.001) and NO release in DOCA-salt rats (+3±1 versus +33±3 fmol/min per gram kidney weight, P<.001) compared with control rats. L-Arg did not influence the time course of systolic blood pressure elevation in DOCA-salt rats (211±5 versus 208±6 mm Hg, DOCA versus L-Arg/DOCA, P=NS). However, oral administration of L-Arg improved acetylcholine- induced declines in renal perfusion pressure (10⁻⁷ mol/L acetylcholine: L-Arg/DOCA, −39±3%, P<.01 versus DOCA). This change was associated with an increase in NO release by acetylcholine (10⁻⁷ mol/L acetylcholine: L-Arg/ DOCA, +10±1 fmol/min per gram kidney weight, P<.05 versus DOCA). However, morphological changes in renal vessels and glomeruli were similar between DOCA and L-Arg/DOCA rats. These results suggest that L-Arg administration partially reverses renal endothelial function with respect to vasorelaxation and NO release independent of blood pressure changes, indicating that hypertensive vessels seem to be depleted of L-Arg and/or have defects in the availability of L-Arg for NO synthesis.