Phosphoinositide turnover in erythrocyte membranes in human and experimental hypertension.
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 (PI-P2) and of phosphatidylinositol 4-phosphate (PI-P) following the incubation of membranes with [gamma-32P] ATP. In untreated essential hypertensives (n = 31) or in hypertensive patients whose blood pressure was controlled by beta-blocker therapy (n = 20), 32P-PI-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-PI-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-PI-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.
Marche
P
P
Koutouzov
S
S
Girard
A
A
Elghozi
J L
JL
Meyer
P
P
Ben-Ishay
D
D
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; D008563:Membrane Lipids; D010716:Phosphatidylinositols; D002118:Calcium