title: Volume expansion during NOS substrate donation with L-arginine: regulatory offsetting of renal response?
abstract: The responses to infusion of nitric oxide synthase substrate (L-arginine 3 mg.kg(-1).min(-1)) and to slow volume expansion (saline 35 ml/kg for 90 min) alone and in combination were investigated in separate experiments. L-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 +/- 2 beats/min) and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 +/- 0.0 to 0.7 +/- 0.1 ml/min). Volume expansion increased arterial blood pressure (102 +/- 3 to 114 +/- 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 +/- 31 micromol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 +/- 1.7 to 1.6 +/- 0.3 pg/ml). Combined volume expansion and L-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 +/- 23 micromol/min at plasma ANG II levels of 3.0 +/- 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, L-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus L-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess.
authors.affiliation: Department of Medical Physiology, University of Copenhagen, DK-2200, Denmark.
authors.forename: Jens Lundbaek
authors.initials: JL
authors.lastname: Andersen
authors.forename: Niels C F
authors.initials: NC
authors.lastname: Sandgaard
authors.forename: Peter
authors.initials: P
authors.lastname: Bie
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001810:Blood Volume / Q000502:physiology*; D003404:Creatinine / Q000378:metabolism; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009994:Osmolar Concentration; D012084:Renin-Angiotensin System / Q000502:physiology; D012964:Sodium / Q000652:urine; D014867:Water / Q000378:metabolism
chemical_list: D014867:Water; D000804:Angiotensin II; D001120:Arginine; D012964:Sodium; D003404:Creatinine; D019001:Nitric Oxide Synthase