Electron Spin Resonance Study of Membrane Abnormality and Microcirculatory Dysfunction in Subjects with Hypertension and the Metabolic Syndrome: In Relation to Endothelial Function and Obesity-associated Vasoactive Substances

Abstract

Abnormalities in physical properties of the cell membranes may strongly be linked to hypertension and other cardiovascular diseases. The purpose of the present review is to elucidate the possible relationships among atherosclerosis, endothelial function, and membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in hypertensive and normotensive subjects using an electron spin resonance (ESR) and spin-labeling method. The ESR study showed that membrane fluidity was significantly decreased in hypertensive subjects compared with normotensive subjects. The reduced membrane fluidity of RBCs was associated with decreased levels of plasma nitric oxide (NO)-metabolites and increased levels of plasma asymmetric dimethylarginine (ADMA: an endogenous NO synthase inhibitor), indicating that endothelial function could be a determinant of membrane fluidity of RBCs. Higher levels of plasma adiponectin were linked to increased membrane fluidity of RBCs. In contrast, elevated levels of plasma homocysteine, oxidative stress, and inflammation were associated with decreased membrane fluidity of RBCs. Intervention with non-pharmacologic therapy (low-salt diet and aerobic physical exercise) and pharmacologic therapy (administration of the Ca channel blocker, benidipine) significantly improved membrane f luidity of RBCs in hypertensive subjects. In this context, it is strongly suggested that atherosclerotic changes might have a close correlation with impaired rheologic behavior of RBCs and microcirculatory dysfunction in hypertension, at least in part, via the NO-dependent mechanism.