In this study we wanted to evaluate the relationship between the ob gene product leptin and blood pressure, as well as plasma renin activity and plasma aldosterone levels. We studied 139 subjects with a mean ؎ ؎ SD age of 50 ؎ ؎ 14 years and a body mass index of 26.5 ؎ ؎ 5.3 kg/m 2 ; 110 subjects had essential hypertension and 29 were healthy nonhypertensive controls. Blood pressure was measured in resting conditions in the morning and blood was drawn for the determination of the plasma renin activity, aldosterone, and leptin levels. The mean blood pressure of the population was 155/97 mm Hg. The relationship between these parameters was studied by univariate regression analysis according to gender and, whenever indicated, adjusted for age and body mass. The mean ؎ ؎ SEM plasma leptin level in the whole population was 9.5 ؎ ؎ 0.6 ng/mL (range, 1.1-43.3). Subjects with stage I hypertension had significantly higher plasma leptin levels than normotensive subjects. Systolic blood pressure correlated with the plasma leptin levels and the leptin levels adjusted for body weight in women (r ‫؍‬ ‫؍‬ 0.422, P < < .01) and nonhypertensive men (r ‫؍‬ ‫؍‬ 0.644, P ‫؍‬ ‫؍‬ .03) only.Plasma renin activity (r ‫؍‬ ‫؍‬ 0.329, P ‫؍‬ ‫؍‬ .03) and aldosterone levels (r ‫؍‬ ‫؍‬ 0.342, P ‫؍‬ ‫؍‬ .026) correlated with the leptin concentration. A significant relationship between the peripheral expression of the ob gene product leptin and systolic blood pressure was found in women and nonhypertensive men. In view of the multiple functions of leptin a causal relationship is postulated and potential mechanisms may involve modulatory effects of leptin on neuropeptide Y, angiotensinogen gene expression, the modulation of the autonomous nervous system, or effects on the pituitary adrenal axis. Direct relationships between both plasma renin activity and aldosterone levels and leptin support the potential importance of the relationship between leptin and blood pressure. Our observation may be of future importance for the understanding of the link between the increase in blood pressure and increasing body weight.

Abstract-This study investigated mechanisms underlying native low-density lipoprotein (LDL)-stimulated proliferation of human vascular smooth muscle cells (VSMC). Experiments were performed to determine whether native LDL affects reactive oxygen species (ROS) formation and activity of extracellular signal-regulated kinase 1/2 (ERK1/2), and whether redox-sensitive pathways contribute to LDL-induced cell proliferation. Native LDL (100 g/mL, 24 hours) increased cell proliferation (to 303 to 388% of control, PϽ0.

The effect of human recombinant platelet‐derived growth factor (PDGF) isoforms, (r)PDGF‐AA, PDGF‐AB and PDGF‐BB, on contractility of rat aortic rings as well as on intercellular free Ca2+ ([Ca2+]i), intracellular pHi (pHi) and thromboxane A2 (TXA2) formation in cultured vascular smooth muscle cells (VSMC) was examined. PDGF‐BB behaved similar to PDGF‐AB and both have features characteristic of conventional vasocontrictor‐agonists that directly increase [Ca2+]i, activate the Na+/H+ exchanger, stimulate the TXA2 formation, and induced contraction in VSMC whereas PDGF‐AA induced contraction without increasing of [Ca2+]i, pHi, and TXA2 formation.

Low density lipoprotein (LDL), at concentrations high enough for receptor binding but not high enough to saturate the receptor, induces activation of phosphatidylinositot (PtdIns) turnover in a variety of cell types with various biological functions. Using both biochemical and electron microscopic studies, we have shown that blood platelets take up and degrade LDL in a manner reminiscent of phagocytic cell types. The activation of both PtdlIns turnover and LDL metabolism is inhibited by high density lipoprotein. Thus, LDL at hormonal concentrations causes general cellular activation.Since all cell types studied responded to LDL with increased PtdIns turnover and uptake of LDL cholesterol, the PtdIns cycle may also be involved in the cellular regulation of LDL cholesterol metabolism.It has recently been demonstrated that low density lipoprotein (LDL), at concentrations in the range of its dissociation constant (Kd) for receptor binding, =1 nM, rapidly affects human platelets in several ways: (i) their shape and ultrastructural morphology are transiently altered; (ii) phosphatidylinositol (PtdIns) turnover and the molar concentration of intracellular free calcium, [Ca2+]i, are increased; and (iii) thromboxane B2 formation is enhanced (1). All of these effects are inhibited by high density lipoprotein fraction 3 (HDL3), which is known to interfere with LDL binding in platelets (2).Studies with fibroblasts have shown that Ca2+-and phospholipid-dependent protein kinase C, which is activated by stimulation ofPtdIns turnover, controls the activity ofcertain enzymes involved in cellular LDL cholesterol (LDL-Chol) metabolism (3-5). This suggests an interrelationship between the PtdIns response and LDL-Chol metabolism, but it is not known whether low concentrations of LDL stimulate the PtdIns cycle in cells other than platelets. Furthermore, it remains to be clarified whether platelets, like other cells, are capable of metabolizing LDL-Chol. Although platelets, which freely exchange cholesterol with plasma under normocholesteremic conditions, are unable to synthesize cholesterol, there is an unexplained increase in the cholesterol-phospholipid ratio in familial and experimental hypercholesterolemia (6-9). Also HDL fractions are known to be internalized and degraded by platelets (10). These findings suggested to us that there might be a catabolic pathway for LDL-Chol in the platelets.We show here that the LDL-induced activation of the PtdIns cycle occurs not only in platelets but also in various cell types that metabolize LDL-Chol, including arterial smooth muscle cells, lung fibroblasts, lymphocytes, and vascular endothelial cells. We also establish that the catabolism of lipoproteins occurs not only in these cell types but also in platelets. Thus, LDL induces general cellular activation at concentrations near the Kd for receptor binding, which appears to be comparable to hormonal effects. MATERIALS AND METHODSLipoprotein Isolation. LDL (density, 1.019-1.063 g/ml) and HDL3 (density, 1.125-1.3 g/ml) were isolate...

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