Objective: Intracellular glutathione in its reduced state is a principal cellular biomolecule with antioxidant activity. Glutathione and homocysteine metabolism are closely associated. As both oxidative stress and hyperhomocystinemia are associated with hypertension, we assessed the relationships between these variables.
Design and setting: An observation-based case-control study, performed at a university teaching hospital.
Patients: Middle-aged male patients with untreated uncomplicated essential hypertension (mean +/- standard deviation age 53.0 +/- 7.2 years, n = 48) before any treatment and controls with similar age distributions (age 51.6 +/- 5.5 years, n = 28) were evaluated.
Methods: In all subjects, the plasma levels of homocysteine, lipids, creatinine, protein, and glucose were measured. Reduced and oxidized glutathione and folic acid were measured from red blood cells (RBC).
Results: The hypertensive patients had decreased levels of red blood cell reduced glutathione (RBC-GSH) and increased levels of oxidized glutathione, which resulted in elevated ratio of oxidized/reduced glutathione as compared to controls (P < 0.001). Plasma homocysteine levels were significantly higher in the hypertensive patients versus the age-matched controls (P < 0.004). In the hypertensive patients, RBC-GSH correlated inversely with systolic blood pressure, serum creatinine, protein and RBC folic acid. No correlation was detected between RBC-GSH and homocysteine. In the controls, RBC-GSH correlated inversely with homocysteine, RBC folic acid and creatinine. According to multiple regression, in the hypertensive patients RBC-GSH was related to systolic blood pressure, hemoglobin, plasma homocysteine, creatinine and protein. Such a relationship was not detected for the controls.
Conclusion: In untreated hypertensive patients both homocysteine and systolic blood pressure are associated with intracellular oxidative stress as determined by RBC-GSH.