Role of glutathione in stabilization of nitric oxide during hypertension developed by inhibition of nitric oxide synthase in the rat.
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 N(G)-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.
Pechánová
O
O
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Kashiba
M
M
Inoue
M
M
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004791:Enzyme Inhibitors; D005978:Glutathione / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester