IngentaConnect Implication of steady state concentrations of nitrite and nitrate...

Authors: Mariko Himeno¹; Takaharu Ishibashi²; Shigeru Nakano¹; Keisuke Furuya¹; Junko Yoshida²; Toshikazu Kigoshi¹; Kenzo Uchida¹; Matomo Nishio²

Source: Clinical and Experimental Pharmacology and Physiology, Volume 31, Number 9, September 2004 , pp. 591-596(6)

Publisher: Blackwell Publishing

Abstract:

Summary

1. The aim of the present study was to determine whether the steady state NO_x concentration reflects NO_x formation in vivo.

2. A NO₃^– load study was performed after achieving NO_x steady state. Chronological changes in NO_x concentrations in plasma and whole blood samples from nine healthy subjects were determined by the HPLC–Griess system and NO_x concentrations in erythrocytes were estimated as a possible NO_x compartment influential in regulating plasma NO_x concentrations.

3. Analysis was performed using the first-order one-compartment open model and the NO_x formation rate was subsequently calculated.

4. The mean (±SEM) steady state NO_x concentration of plasma (15.5 ± 1.6 µmol/L), whole blood (12.8 ± 1.2 µmol/L) and erythrocytes (11.9 ± 0.7 µmol/L) did not correlate with the NO_x formation rate in the compartments (0.50 ± 0.05, 0.61 ± 0.04 and 0.91 ± 0.17 µmol/kg per h, respectively), whereas a significant correlation was found between the steady state NO_x concentration and NO_x elimination rate (K_el) in plasma (r = -0.69; P = 0.04) and whole blood (r = -0.79; P = 0.01).

5. Although there was no direct correlation between steady state NO_x concentrations and serum creatinine levels, the correlation between half-life and serum creatinine levels was significant (plasma: r = 0.60, P = 0.02; whole blood: r = 0.49, P = 0.04).

6. Plasma NO_x concentrations correlated significantly with erythrocyte NO_x concentrations (r = 0.92, P < 0.01; erythrocyte NO_x = 0.66 × plasma NO_x).

7. The results of the present study indicate that NO_x does not accumulate excessively into erythrocytes at steady state and during a NO₃^– load and that the steady state NO_x concentration in whole blood and plasma preferentially implies NO_x elimination (mainly depending on renal function) rather than NO_x formation.

Keywords: blood; erythrocytes; nitrate; nitric oxide; nitrite; plasma; steady state

Document Type: Research article

DOI: 10.1111/j.1440-1681.2004.04060.x

Affiliations: 1: Division of Endocrinology, Department of Internal Medicine and 2: Department of Pharmacology, Kanazawa Medical University, Uchinada, Ishikawa, Japan

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Implication of steady state concentrations of nitrite and nitrate metabolites of nitric oxide in plasma and whole blood in healthy human subjects