phosphatidylinositol-4-phosphate and Hypertension

Undernutrition during childhood leads to chronic diseases in adult life including hypertension, diabetes and chronic kidney disease. Here we explore the hypothesis that physiological alterations in the bioactive lipids pattern within kidney tissue might be involved in the progression of chronic kidney disease.. Membrane fractions from kidney homogenates of undernourished rats (RBD) were submitted to lipid extraction and analysis by thin layer chromatography and cholesterol determination.. Kidneys from RBD rats had 25% lower cholesterol content, which disturb membrane microdomains, affecting Ca. Results point to an imbalance in the bioactive lipid generation with further consequences to key events related to kidney function, thus contributing to the establishment of chronic kidney disease.

Topics: 1-Phosphatidylinositol 4-Kinase; Animals; Animals, Newborn; Ceramides; Cholesterol; Diacylglycerol Kinase; Gene Expression Regulation; Hypertension; Kidney; Lipid Metabolism; Male; Malnutrition; Membrane Microdomains; Phosphatidic Acids; Phosphatidylinositol Phosphates; Phospholipases A2; Phosphotransferases (Alcohol Group Acceptor); Rats; Rats, Wistar; Renal Insufficiency, Chronic

The effects of substance P on inositol phospholipids of adrenal medulla slices from spontaneously hypertensive and normotensive Wistar-Kyoto rats were investigated. Substance P reduces [32P] incorporation into inositol phospholipids of both rat strains. This effect was most expressed in hypertensive rats, which showed a higher basal 32P incorporation into phosphatidylinositol phosphates compared to normotensive control rats (probably due to the higher turnover of monoester-phosphate groups). Substance P causes a less potent diesteratic hydrolysis of [3H]inositol prelabelled phospholipids in spontaneously hypertensive rats compared with Wistar-Kyoto rats. A possible consequence of the reduced diesteratic hydrolysis by endogenous substance P and related substances of inositol phospholipids in adrenal medulla from spontaneously hypertensive rats is discussed.

Topics: Adrenal Medulla; Animals; Hydrolysis; Hypertension; Inositol; Male; Phosphates; Phosphatidic Acids; Phosphatidylcholines; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phosphatidylinositols; Phosphatidylserines; Phosphorus Radioisotopes; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Substance P

The metabolism of phosphoinositides was investigated in erythrocyte membranes of essential hypertensive patients, normotensive offspring of hypertensive patients and matched controls. Measurement of 32P-labelling of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate revealed no differences in the rate of incorporation of the isotope in essential hypertensive patients compared with controls. In the normotensive offspring of essential hypertensive patients there was a highly significant increase in the rate of 32P incorporation (P less than 0.01), compared with matched controls, indicating a higher rate of metabolic turnover in these subjects. These data demonstrate that phosphoinositide metabolism is enhanced in subjects genetically at risk of hypertension, before the blood pressure has risen, but once the blood pressure is established, it is no different from control values. Abnormal phosphoinositide metabolism may be a further manifestation of a genetically determined defect of membrane physicochemical function underlying essential hypertension.

Topics: Erythrocyte Membrane; Female; Humans; Hypertension; Male; Middle Aged; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositol Phosphates; Phosphatidylinositols