Insulin, Leptin, and Membrane Microviscosity in Blood Pressure Regulation

Insulin, Leptin, and Membrane Microviscosity in Blood Pressure Regulation To the Editor: We read with great interest the recent article by Vecchione and colleagues1 dealing with a possible link between insulin and leptin in the regulation of vascular tone in rats.1 The results of their presented study demonstrated that insulin and leptin cooperated in the modulation of vascular tone through enhancement of endothelial nitric oxide (NO) release. Vecchione et al proposed that direct cross-talk between insulin and leptin at the vascular level could have a major impact on the regulation of cardiovascular system in metabolic disorders and hypertension. Numerous studies have already shown a strong relationship between obesity and hypertension.2,3 However, the contribution of insulin and leptin to the pathogenesis of hypertension is not fully understood. Recently, Sela et al4 demonstrated that polymorphonuclear leukocytes (PMN) in essential hypertension showed increased level of intracellular calcium content correlating positively with the individual’s blood pressure and plasma insulin. They proposed that, because PMN priming may lead to oxidative stress and inflammation, intracellular calcium and insulin are involved in the pathogenesis of hypertension-induced vascular injury. In a study we presented earlier, a relationship between membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes and insulin was investigated in essential hypertension by means of an electron paramagnetic resonance method.5 The membrane fluidity of erythrocytes was significantly lower in patients with essential hypertension than in normotensive subjects. In addition, it was demonstrated that the higher the plasma insulin level, the lower the membrane fluidity of erythrocytes, which might indicate that hyperinsulinemia might be involved in the regulation of membrane fluidity of erythrocytes in essential hypertension. In an in vitro study, we showed that insulin alone and in combination with calcium decreased membrane fluidity of erythrocytes in essential hypertension.6 It is likely that the insulin-evoked decrease in membrane fluidity of erythrocytes may partially be mediated by the increased intracellular calcium content.7 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 hypertension.8,9 One hypothesis is that insulin might accelerate abnormalities in intracellular calcium metabolism and membrane function in blood cells such as PMN and erythrocytes, which could partially explain the vascular complications in hypertensive subjects with hyperinsulinemia. In contrast, it was demonstrated that leptin significantly increased the membrane fluidity of erythrocytes and improved the rigidity of cell membranes via the NOand cGMP-dependent mechanism.10 The result might be consistent with the finding of Vecchione et al showing that leptin enhanced NO release. It is possible that insulin and leptin may exert opposite effects on membrane microviscosity of erythrocytes, although the precise mechanism underlying their modulatory effects on the membrane function is still uncertain. In this context, it can be speculated that a functional interaction between insulin and leptin may differ among tissues. It would be necessary to assess more precisely the roles of insulin and leptin and their contribution to the pathophysiology of hypertension.