Exaggerated natriuresis during clamping of systemic NO supply in normal man
Abstract
Nitric oxide (NO) may be involved in fluid homeostasis. 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 Nω-nitro-L-arginine methyl ester (L-NAME, 750 µg*(kg body weight)-1 bolus and 8.3 µg*kg-1*min-1) and sodium nitroprusside, the latter at a rate preventing the L-NAME from increasing total peripheral resistance ('NO-clamping'). Slow volume expansion (saline, 20 µmol NaCl*kg-1*min-1 for 3 h) was performed with and without concomitant NO-clamping. NO-clamping per se decreased renal plasma flow (RPF, P ~0.02) and tended to decrease arterial blood pressure (MABP). Volume expansion markedly decreased the plasma levels of renin, angiotensin II (AngII), and aldosterone (all P <0.001), while MABP (oscillometry), heart rate, cardiac output (impedance cardiography), RPF (by p-aminohippurate), glomerular filtration rate (GFR by 51Cr-ethylenediaminetetraacetate), plasma [Na+] and [K+] remained constant. Volume expansion increased sodium excretion (P <0.02) at constant filtered load; however, more so during NO-clamping than during control (+184% vs. 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 homeostatic response to saline loading, but the specific mechanisms of the hypernatriuresis remain obscure.
Domains
Human health and pathology
Origin : Files produced by the author(s)
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