title: Long-term administration of L-arginine improves nitric oxide release from kidney in deoxycorticosterone acetate-salt hypertensive rats.
abstract: 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 mmHg, 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.
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hirata
authors.forename: E
authors.initials: E
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Kikuchi
authors.forename: T
authors.initials: T
authors.lastname: Nagano
authors.forename: M
authors.initials: M
authors.lastname: Hirobe
authors.forename: M
authors.initials: M
authors.lastname: Omata
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D010477:Perfusion; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride; D013997:Time Factors
chemical_list: D009569:Nitric Oxide; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D001120:Arginine; D000109:Acetylcholine