Ol'ga Pechanova1, Misato Kashiba2 and Masayasu
Inoue2
1Institute of Normal and Pathological Physiology, Slovak Academy
of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovak Republic
2Department of Biochemistry, Osaka City University Medical School,
Osaka 545 - 8585, Japan
Abstract: The present study examined the role of glutathione
in the development of hypertension induced by long-term inhibition of nitric
oxide (NO)-synthase. Three groups of rats were investigated: control group,
L-NAME group: group with NO-synthase inhibition by NG-nitro-l-arginine
methyl ester (L-NAME, 40 mg/kg per day) for 2 weeks, and BSO group: group
with glutathione synthesis inhibitor l-buthionine sulfoximine (BSO, 1.4
mmol/kg per 12 h) for 3 days. All the groups were subjected to an acute
i.v. experiment in which the given substances were exchanged between groups.
There was no change in systolic blood pressure (SBP) in the control group
after 1 and 2 h of acute BSO (1.4 mmol/kg, i.v.) treatment. In the L-NAME
group, SBP increased significantly by 10% after 2 h of acute BSO treatment.
In the BSO group, SBP did not change vs control; however, after 2 h of acute
L-NAME (10 mg/kg, i.v.) treatment, the increase in SBP exceeded by 12% (P<0.05)
that of the control group. Along with the increase in SBP, acute BSO treatment
significantly potentiated the decrease in plasma nitrite/nitrate concentration
in the L-NAME group. The acute BSO-induced glutathione decrease was significantly
greater in the L-NAME group than in the control group. In NO-deficient hypertensive
rats, the results are indicative of a decrease in glutathione synthesis
and a stabilizing role of glutathione.
Keywords: Glutathione, Nitric oxide (NO), NO-synthase, NG-nitro-l-arginine
methyl ester, Hypertension