Hypertension, which is characterized by multiple alterations in the structure and function of the cell membrane, is often associated with important metabolic abnormalities including those concerning lipid metabolism. Dyslipidemia accompanying essential hypertension consists of elevated plasma triglycerides, low HDL cholesterol, and increased levels of atherogenic LDL cholesterol particles. The altered membrane microviscosity seen in hypertensive subjects reflects the changes of membrane lipid composition resulting from intensive exchange between circulating and membrane lipids, as well as from abnormal cellular lipid synthesis and metabolism. The changes of membrane microviscosity are known to modulate the activity of proteins involved in ion transport, signal transduction, cell Ca 2؉ handling, intracellular pH regulation, etc. Alterations in plasma or membrane lipids are indeed closely associated with ion transport abnormalities as well as with impaired control of cytosolic Ca 2؉ T here is no doubt that essential hypertension is associated with multiple membrane alterations, including changes in membrane microviscosity, receptor function, signal transduction, ion transport, calcium mobilization, intracellular pH regulation, and so on. Lipids, as an integral part of the cell membrane, play a decisive role in the modulation of the membrane properties mentioned. Specific lipid-lipid and lipid-protein interactions result in a highly dynamic but precisely controlled architecture of membrane components. Major regulators of membrane architecture are membrane potential, intracellular Ca 2ϩ and pH, lipid composition, cell-to-cell contact, and membrane coupling with the cytoskeleton or extracellular matrix. Intermolecular associations in the membrane and at the membrane-cytoskeleton interface are further selectively controlled by specific phosphorylation and dephosphorylation cascades involving both proteins and lipids. This is regulated by the extracellular matrix as well as by the binding of growth factors and hormones to their specific receptors. 1,2The aim of this review is to outline some interrelationships between abnormal lipid metabolism and altered membrane structure or function in human and experimental hypertension, and to evaluate whether abnormal lipid metabolism, which is responsible for a great part of membrane abnormalities found in hypertension, might be an integral part of its pathogenetic mechanisms. BLOOD PRESSUREMultiple metabolic abnormalities often accompany essential hypertension. Decreased high-density lipoproteins (HDL) together with increased plasma levels of low-density (LDL) and very low-density lipoproteins (VLDL), as well as hypertriglyceridemia, hypercholesterolemia, and insulin resistance, were found in many hypertensive patients. 3,4 There is increasing evidence for a genetic basis for the association of hypertension with insulin resistance and dyslipidemia. The genetic locus associated with dyslipidemia accompanying hypertension or diabetes seems to be closely linked to the LDL recept...

In this review, we attempt to outline the age-dependent interactions of principal systems controlling the structure and function of the cardiovascular system in immature rats developing hypertension. We focus our attention on the cardiovascular effects of various pharmacological, nutritional, and behavioral interventions applied at different stages of ontogeny. Several distinct critical periods (developmental windows), in which particular stimuli affect the further development of the cardiovascular phenotype, are specified in the rat. It is evident that short-term transient treatment of genetically hypertensive rats with certain antihypertensive drugs in prepuberty and puberty (at the age of 4-10 wk) has long-term beneficial effects on further development of their cardiovascular apparatus. This juvenile critical period coincides with the period of high susceptibility to the hypertensive effects of increased salt intake. If the hypertensive process develops after this critical period (due to early antihypertensive treatment or late administration of certain hypertensive stimuli, e.g., high salt intake), blood pressure elevation, cardiovascular hypertrophy, connective tissue accumulation, and end-organ damage are considerably attenuated compared with rats developing hypertension during the juvenile critical period. As far as the role of various electrolytes in blood pressure modulation is concerned, prohypertensive effects of dietary Na+ and antihypertensive effects of dietary Ca2+ are enhanced in immature animals, whereas vascular protective and antihypertensive effects of dietary K+ are almost independent of age. At a given level of dietary electrolyte intake, the balance between dietary carbohydrate and fat intake can modify blood pressure even in rats with established hypertension, but dietary protein intake affects the blood pressure development in immature animals only. Dietary protein restriction during gestation, as well as altered mother-offspring interactions in the suckling period, might have important long-term hypertensive consequences. The critical periods (developmental windows) should be respected in the future pharmacological or gene therapy of human hypertension.

No abstract