Biomedical subjects

S Brovkovych

Publications and source records attributed to S Brovkovych.

3 recordsLinked to original sources

PubMed2001

Nitric oxide measurements during endotoxemia.

BACKGROUND: Excessive continuous NO release from inducible NO synthase over prolonged periods under pathological conditions, such as endotoxemia, contributes significantly to circulatory failure, hypotension, and septic shock. This NO production during endotoxemia is accompanied by superoxide release, which contributes to the fast decay of NO. Therefore, the amount of NO that diffuses to target sites may be much lower than the total amount released under pathological conditions. METHODS: We performed in vivo and ex vivo measurements of NO (electrochemical) and ex vivo in situ measurements of superoxide, peroxynitrite (chemiluminescence), and nitrite and nitrate (ultraviolet-visible spectroscopy). We determined the effect of lipopolysaccharide administration (20 mg/kg) on diffusible NO, total NO (diffusible plus consumed in chemical reactions), and superoxide and peroxynitrite release in the pulmonary arteries of rats. RESULTS: An increase in diffusible NO generated by constitutive NO synthase was observed immediately after administration of lipopolysaccharide, reaching a plateau (145 +/- 18 nmol/L) after 540 +/- 25 s. The plateau was followed by a decrease in NO concentration and its subsequent gradual increase after 45 min because of NO production by inducible NO synthase. The concentration of superoxide increased from 16 +/- 2 nmol/L to 30 +/- 3 nmol/L after 1 h and reached a plateau of 41 +/- 4 nmol/L after 6 h. In contrast to the periodic changes in the concentration of diffusible NO, the total concentration of NO measured as a sum of nitrite and nitrate increased steadily during the entire period of endotoxemia, from 2.8 +/- 0.2 micromol/L to 10 +/- 1.8 micromol/L. CONCLUSIONS: The direct measurement of NO concentrations in the rat pulmonary artery demonstrates dynamic changes throughout endotoxemia, which are related to the production of superoxide and the subsequent increase in peroxynitrite. Monitoring endotoxemia with total nitrate plus nitrite is not sensitive to these fluctuations in NO concentration.

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PubMed1999

Nitric oxide release from normal and dysfunctional endothelium.

The endothelium plays a critical role in maintaining vascular tone by releasing vasoconstrictor and vasodilator substances. Endothelium - derived nitric oxide (NO) is a vasodilator rapidly inactivated by superoxide (O2-) found in significant quantities. The porphyrinic sensor (0.5-8 microm diameter) and chemiluminescence methods were used to measure NO and (O2-) respectively. Effects of hypertension, low density lipoprotein (LDL), and heart preservation on the release of NO and O2- were delineated. In the single endothelial cell (rat aorta) NO concentration was the highest in the cell membrane decreasing exponentially with distance from cell, and becoming undetectable beyond 50 microm and 25 microm for normotensive (WKY) and hypertensive (SHR) rats respectively. The endothelium of SHR released 40% less NO (300+/-25 nmol L(-1)) than that of normotensive rats (500+20 nmol L(-1)), due to the higher production of O2- in SHR rats. An exponentially decreasing NO production (from 1.20 +/- 0.15 to 0.16 +/- 0.05 micromol (L-1)) and concomitant increase of O2- generation (from 10 +/- 0.3 to 300 +/- 25 nmol L(-1) were observed in left ventricle of stored (eight hours) rabbit heart. Native and oxidized low density lipoproteins (nLDL and oxLDL) inhibited NO generation and increased O2- production. The local depletion of the L-arginine substrate may disarrange the nitric oxide synthase, leading to production of O2- from oxygen.

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PubMed1997

In situ measurement of nitric oxide, superoxide and peroxynitrite during endotoxemia.

We report in vivo and ex vivo measurements of nitric oxide (electrochemical), ex vivo in situ measurements of superoxide (chemiluminescence) and peroxynitrite (chemiluminescence) and delineate the effect of endotoxemia on nitric oxide, superoxide and peroxynitrite release in aorta of rats. Nitric oxide release was measured in the aorta wall. An increase of nitric oxide concentration was observed immediately after administration of lipopolysaccharide (Escherichia coli serotype 0127: B8, 20 mg/kg), reaching a plateau ((50 nmol/L) after 180 +/- 50 seconds; the plateau was followed by decreasing nitric oxide concentration and its subsequent gradual small increase after 45 minutes. Superoxide and peroxynitrite production increased dramatically during endotoxemia. Superoxide concentration increased from 10 +/- 2 nmol/L to 28 +/- 3 nmol/L at one hour, and reached a 50 nmol/L plateau at 4 hours. The pattern of peroxynitrite release paralleled the pattern of superoxide release during the time course of endotoxemia. Diametrical alteration of nitric oxide and superoxide concentration with subsequent production of peroxynitrite may be a major cause of endothelial cell injury during endotoxemia.

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