ISSN:
1440-1681
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
〈list xml:id="l1" style="custom"〉1Endothelium-derived nitric oxide (NO), a major modulator of vascular tone, is synthesized from the terminal guanidino nitrogen of l-arginine. This reaction is inhibited by analogues of l-arginine, such as N-nitro-l-arginine methyl ester (l-NAME). Many of the biological effects of NO are mediated by the second messenger cGMP. NO is rapidly oxidized to NO3− which, like cGMP, is eliminated via excretion into the urine. In a placebo controlled study, we investigated whether oral bolus administration of l-arginine and l-NAME affects the urinary excretion rates of NO3− and cGMP in Munich Wistar Frömmter (MWF) rats.2Twenty MWF rats were kept in metabolic cages and received l-arginine (3 g/kg body weight), l-NAME (50mg/kg), or placebo (0.9% saline) in randomized order. Urine samples were sequentially collected for 10 h and analysed for creatinine, NO3− and cGMP.3l-Arginine induced a slight, but prolonged increase in urine flow, whereas l-NAME induced an early, transient increase in urine flow which was followed by a decrease. Creatinine clearance decreased by 65% after l-NAME, but was not affected by l-arginine or placebo.4Urinary NO3− and cGMP excretion rates transiently increased after l-arginine (NO3−: + 29%; cGMP: + 16%) for 4–5h, whereas l-NAME induced an immediate, pronounced and lasting inhibition of urinary NO3− and cGMP excretion (NO3−:-76%; cGMP:-46%). Urinary NO3− and cGMP excretions were significantly correlated (r = 0.755; P〈 0.001).5Urinary excretion rates of NO3− and cGMP, expressed as μmol/h, were correlated to urine flow (mL/h; r = 0.617 and 0.649, respectively; both P〈0.05), whereas after correction by urinary creatinine (μmol/mmol creatinine) no correlation with urine flow was observed, indicating that these excretion rates were independent of renal excretory function. Thus we conclude that changes in the urinary excretion rates of NO3− and cGMP represent changes in NO production rates in vivo when expressed in relation to urinary creatinine. Urinary NO3− and cGMP excretion is modulated by acute NO synthase inhibition or substrate provision.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1440-1681.1996.tb03055.x
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