To the Editor:

We note with interest the study by Redon et al¹ on antioxidant activities and oxidative stress byproducts in human hypertension. The authors have reported an increase in oxidative stress and a reduction in the activity of antioxidant mechanisms in hypertensive subjects which appeared to be independent of the blood pressure levels. Although oxidative stress is known to occur in hypertension, direct cause-and-effect relationships have not been clearly delineated. Several factors inherent to hypertensive status such as enhanced activity of angiotensin II, hyperinsulinemia, and increased NAD(P)H oxidase activity have been implicated in inducing altered oxidative state in hypertension. Oxidative stress has been seen to promote the entry of Ca²⁺ into vascular myocytes, stimulating neointimal hyperplasia and vasoconstriction.² Although no relationship between oxidative stress and blood pressure values was observed by Redon et al,¹ such a relationship cannot be excluded. In fact, we have observed a significant negative correlation between diastolic blood pressure and several endogenous antioxidants in hypertensive patients. We found a negative correlation between glutathione-S-transferase (GST; r=−0.52), glutathione peroxidase (GPx; r=−0.46), ascorbic acid (r=−0.40), and non-protein thiols (r=−0.482). The levels of GST, GPx, ascorbic acid, and non-protein thiols were observed to be significantly low in hypertensives as compared with normotensives. We also observed a significant decrease in plasma ferric-reducing antioxidant power (FRAP) in hypertensives as compared to normotensive controls, which also showed a negative correlation (r=−0.52) with diastolic pressure. FRAP is a direct indicator of antioxidant status and measures endogenous reduction of Fe⁺³ to Fe⁺². A low FRAP activity would lead to increased Fe⁺³, which is a potent pro-oxidant and would result in increased oxidative stress. The increased oxidative stress observed in hypertensive patients could lead to endothelial dysfunction by increasing intracellular Ca levels. Antioxidants such as probucol and ascorbic acid have been shown to improve endothelium-dependent relaxation, suggesting the role of reactive oxygen species (ROS) in endothelial dysfunction. Redon et al¹ have also proposed that ROS products released from peripheral mononuclear cells may also contribute to endothelial dysfunction and organ damage present in hypertensive subjects. We have observed significantly lower nitric oxide levels in hypertensive patients. There was, however, no correlation between severity of disease, organ damage, and plasma nitric oxide levels. Patients on antihypertensive therapy (Ca channel blockers or ACE inhibitors) showed a significant increase in nitric oxide levels, but their antioxidant levels remained lower as compared with normotensives. Thus, there appear to be other factors contributing to oxidative stress, which need to be further investigated.