These data demonstrate that obesity augments prostanoid-dependent vasoconstriction and markedly increases vascular thromboxane receptor gene expression. These changes are likely to promote the development of vascular disease, hypertension and thrombosis associated with obesity.
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.
A single antibody RIA method for measurement of plasma cortisol concentrations in the bull is described. Antisera were obtained from rabbits immunized against cortisol-3-oxime-bovine serum albumin. By this technique, peripheral cortisol levels were determined in seven adult bulls (one blind) during 24- and 48-h periods, with blood collections every 30 min. Statistical evaluation of the 24-h profiles using time series analysis revealed that cortisol is secreted episodically throughout the day-night cycle (range, 0.4-9.7 ng/ml). Despite individual variability in both frequency and amplitude of secretory episodes, a distinct circadian secretion pattern was recognized. After dividing the 24 h into three 8-h time periods (I, 0900-1700 h; II, 1700-0100 h; III, 0100-0900 h), a depressed secretory activity with small episodic bursts not exceeding 3.5 ng/ml plasma consistently occurred during time period II. Increased cortisol secretion with high fluctuating levels was evident during time periods I and III. Maximum cortisol concentrations greater than 8 ng/ml were noticed in the morning at the onset of daylight, whereas lowest values were recorded in the evening when darkness began. Results from this study indicate that there is a temporal correlation between the rhythm of cortisol secretion and the light-dark cycle in the bovine species.
Human platelet-derived growth factor (PDGF) is mainly composed of two polypeptide chains (PDGF-AB). All three possible dimeric forms of PDGF-i.e., PDGF-AA, PDGF-BB and PDGF-AB-exist in nature. We have used two recombinant PDGF homodimers to determine the roles of each isoform in the activation of phosphatidylinositol turnover in vascular smooth muscle cells (VSMC) isolated from rat thoracic aorta, their mitogenic effect on VSMC, and their vasoconstrictor effect on intact strips of aortic vascular tissue. Three Ca2 -channel blockers, nifedipine, verapamil, and diltiazem, were used as antagonists for investigating the PDGFdependent changes mediated by the homodimers. PDGF-BB had a greater efficacy than PDGF-AA on inositol 1,4,5-trisphosphate release, on the formation of diacylglycerol, and on Ca2+ mobilization, which was also associated with vasoconstrictor activity and effective mitogenicity. PDGF-AA, on the other hand, was more potent than PDGF-BB in stimulating protein kinase C. In all instances, the activation of the phosphatidylinositol turnover by the two homodimers was inhibited by the Ca2+-channel blockers.
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