Stains and Nitric Oxide Production Against Ischemic Stroke
To the Editor:
We wish to respond to the article by Dr Reeves and colleagues1 dealing with the effect of pretreatment of statins on ischemic stroke outcomes. The results of their study demonstrated that pretreatment of statins was associated with an approximately 40% reduction in the odds of poor stroke outcomes in whites. In contrast, the authors indicated that statins increased poor stroke outcomes, although not significantly, in blacks. The authors proposed that pretreatment of statins was associated with better stroke outcomes in whites, but not in blacks, suggesting the possiblility of different effects of statins among whites and blacks with ischemic stroke.
Evidence indicates that nitric oxide (NO) may actively participate in neuroprotection in cerebral ischemia. In a study we presented previously, a relationship between membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes and NO was investigated by means of an electron paramagnetic resonance method.2 The decreased membrane fluidity of erythrocytes might cause a disturbance in the blood rheological behavior and the microcirculation, which could contribute, at least in part, to the pathophysiology of circulatory disorders. We demonstrated that NO increased the membrane fluidity of erythrocytes and improved the rigidity of cell membranes in humans. In the separate series of the study, we showed that the lower membrane fluidity of erythrocytes was associated with decreased levels of plasma NO-metabolites and increased levels of asymmetrical dimethylarginine (an endogenous inhibitor of NO synthase).3 One hypothesis is that NO would be a defense against vascular complications in circulatory disorders. Recently, it was shown that the statin restored endothelial function independent of changes in low-density lipoprotein.4 In addition, it was demonstrated that endothelium-dependent vasodilation might be reduced in black individuals compared with white individuals,5 indicating that racial differences may exist in endothelial function and NO-bioavailability. In this context, we speculate that racial differences in NO production might partially explain the differential effects of statins among whites and blacks with ischemic stroke. Therefore, we would like to know whether endothelial function might be altered between white and black populations in the study of Dr Reeves and colleagues. It would be necessary to assess more precisely the functional interactions between statins and NO, and their contribution to the prevention of ischemic stroke.
Reeves MJ, Gargano JW, Luo Z, Mullard A, Jacobs BS, Majid A. Effect of pretreatment with statins on ischemic stroke outcomes. Stroke. 2008; 39: 1779–1785.
Beckman JA, Liao JK, Hurley S, Garrett LA, Chui D, Mitra D, Creager MA. Atorvastatin restores endothelial function in normocholesterolemic smokers independent of changes in low-density lipoprotein. Circ Res. 2004; 95: 217–223.