Phosphoinositide Turnover in Erythrocyte Membranes in Human and Experimental Hypertension


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Abstract

The metabolism of phosphoinositides, a class of membrane lipids involved in Ca2+ -transport and/or mobilization systems, was investigated in patients with moderate essential hypertension and in Sabra rats. Experiments were performed in vitro on isolated erythrocyte membranes by measuring the 32P-labelling of phosphatidylinositol 4,5-bisphosphate (Pl-P2) and of phosphatidylinositol 4-phosphate (Pl-P) following the incubation of membranes with [γ -32P] ATP. In untreated essential hypertensives (n=31) or in hypertensive patients whose blood pressure was controlled by beta-blocker therapy (n=20), 32P-Pl-P2 was significantly higher than in normotensive controls (n=30); no significant difference was observed between the two groups of hypertensive patients. In Sabra rats fed on a low Na diet, 32P-Pl-P2 levels were significantly higher in hypertensive-prone animals (SBH) than in hypertensive-resistant animals (SBN). When the animals were fed a high Na diet or were DOCA/ salt treated, 32P-Pl-P2 did not change in either substrain, although such conditions differentially affected the blood pressure of SBH and SBN. Our data indicate that the modification of phosphoinositide metabolism is not a consequence of the blood pressure elevation, but can be considered as an intrinsic membrane defect which may be associated with functional alterations of Ca2+ fluxes which in hypertensives result in an enhanced intracellular Ca2+ level.

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