| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
In the first series of the experiments, we describe the results regarding the Ca-sensitivity and neurotransmitter release in hypertension. The Ca channel blocker, nicardipine, significantly inhibited the stimulation-evoked norepinephrine release and vasoconstrictor responses in rat mesenteric arteries. The inhibitory effect was more pronounced in spontaneously hypertensive rats(SHR) than in age-matched normotensive Wistar-Kyoto(WKY) rats.
In the second series of the study, in order to assess the possible link among hypertension, obesity and diabetes mellitus, we investigated the mechanisms of actions of insulin and leptin on membrane function in subjects with hypertension. Membrane fluidity is a physicochemical feature of biomembranes and is an important factor modulating microcirculation. Using the electron paramagnetic resonance and spin-labeling method, we examine the alterations in membrane fluidity of erythrocytes in hypertensive subjects with obesity and diabetes mellitus. We demo
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nstrated that the higher plasma insulin level, the lower the membrane fluidity of erythrocytes. This might indicate that hyperinsulinemia is involved in the regulation of membrane fluidity of erythrocytes. In an in vitro study, we showed that insulin alone and in combination with calcium decreased the membrane fluidity of erythrocytes. The decreased membrane fluidity of erythrocytes might cause a disturbance in the blood rheologic behavior and the microcirculation, which could contribute, at least in part, to the pathophysiology of hypertension. One hypothesis is that insulin might accelerate abnormalities in intracellular Ca-metabolism and membrane functionin erythrocytes, which could partially explain the vascular complications in subjects with hyperinsulinemia. On the other hand, it was demonstrated that leptin increased the membrane fluidity of erythrocytes and improved the rigidity of cell membranes via the nitric oxide(NO)-and cGMP-dependent mechanism, suggesting that insulin and leptin may exert opposite effects on membrane microviscosity of erythrocytes.
In this context, we speculate that abnormalities in membrane function and Ca-metabolism might contribute, at least in part, to the pathophysiology of hypertension with obesity and diabetes mellitus. Less
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