title: Exaggerated natriuresis during clamping of systemic NO supply in healthy young men.
abstract: NO (nitric oxide) may be involved in fluid homoeostasis. We hypothesized that increases in NO synthesis contribute to acute, saline-induced natriuresis, which, therefore, should be blunted when NO availability is stabilized. Young men were studied during simultaneous infusions of L-NAME [NG-nitro-L-arginine methyl ester; bolus of 750 μg·kg⁻¹ of body weight and 8.3 μg·min⁻¹·kg⁻¹ of body weight] and SNP (sodium nitroprusside), the latter at a rate preventing L-NAME from increasing total peripheral resistance ('NO-clamping'). Slow volume expansion (saline, 20 μmol of NaCl·min⁻¹·kg⁻¹ of body weight for 3 h) was performed with and without concomitant NO-clamping. NO-clamping itself decreased RPF (renal plasma flow; P~0.02) and tended to decrease arterial blood pressure [MABP (mean arterial blood pressure)]. Volume expansion markedly decreased the plasma levels of renin, AngII (angiotensin II) and aldosterone (all P<0.001), while MABP (oscillometry), heart rate, cardiac output (impedance cardiography), RPF (by p-aminohippurate), GFR [glomerular filtration rate; by using 51Cr-labelled EDTA] and plasma [Na+] and [K+] remained constant. Volume expansion increased sodium excretion (P<0.02) at constant filtered load, but more so during NO-clamping than during control (+184% compared with 52%; P<0.0001). Urinary nitrate/nitrite excretion increased during volume expansion; plasma cGMP and plasma vasopressin were unchanged. The results demonstrate that NO-clamping augments sodium excretion in response to volume expansion at constant MABP and GFR, reduced RPF and decreased renin system activity, a response termed hypernatriuresis. The results indicate that mediator(s) other than MABP, RPF, GFR and renin system activity contribute significantly to the homoeostatic response to saline loading, but the specific mechanisms of hypernatriuresis remain obscure.
authors.affiliation: Institute of Molecular Medicine, University of Southern Denmark, and Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark. Jane.Simonsen@ouh.regionsyddanmark.dk
authors.forename: Jane A
authors.initials: JA
authors.lastname: Simonsen
authors.forename: Mona S
authors.initials: MS
authors.lastname: Rasmussen
authors.forename: Werner
authors.initials: W
authors.lastname: Vach
authors.forename: Poul F
authors.initials: PF
authors.lastname: Høilund-Carlsen
authors.forename: Peter
authors.initials: P
authors.lastname: Bie
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008954:Models, Biological; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009318:Natriuresis / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000008:administration & dosage; D017595:Renal Plasma Flow / Q000187:drug effects / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012965:Sodium Chloride / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D000804:Angiotensin II; D009599:Nitroprusside; D009569:Nitric Oxide; D012965:Sodium Chloride; D000450:Aldosterone; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester