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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is associated with profound alterations of the cardiovascular system including an increase in systemic blood pressure. Several vasoactive factors, including non-esterified fatty acids, angiotensin II, prostaglandins, and nitric oxide are known to be produced by adipose tissue, and are therefore of particular interest regarding their potential role for the regulation of vascular tone and structure. In addition, central nervous system actions of the adipose tissue-derived hormone leptin may contribute to increased sympathetic nervous system activity that is typically found in obesity. Enhanced leptin-driven renal sympathetic out-flow, in combination with low atrial natriuretic peptide plasma levels possibly due to over-expression of the natriuretic peptide clearance receptor in adipocytes, may enhance sodium retention and volume expansion, both key features in the pathophysiology of obesity-associated hypertension. In this review, we discuss these and other possible contributions of adipose tissue to the regulation of cardiovascular-renal function and speculate on the role of adipose tissue for the development of obesity-associated hypertension.
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PMID:Role of adipose tissue for cardiovascular-renal regulation in health and disease. 1124 14

Hypertension develops in almost 60% of obese individuals. Apart from the recent observation of obesity-associated structural changes in kidney structure that may lead to enhanced tubular sodium reabsorbtion, reports of paracrine and hormonal factors derived from adipose tissue have prompted speculations about the role of adipose tissue in the pathophysiology of obesity-induced hypertension. We summarize recent data on leptin's sympathoexcitatory actions, the possible influence of adipose tissue on atrial natriuretic peptide levels, and the formation of vasoactive substances, such as angiotensin II and nonesterified fatty acids, by adipocytes. The mechanisms discussed herein may contribute to the typical findings in obesity-induced hypertension, including volume expansion, sodium retention, enhanced sympathetic nervous system activity, increased activity of the systemic renin-angiotensin system, low atrial natriuretic peptide levels, and disturbed glucose and insulin metabolism. Together, these data strengthen the hypothesis that adipose tissue is potentially a major regulator of cardiovascular-renal function.
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PMID:New developments in mechanisms of obesity-induced hypertension: role of adipose tissue. 1127 98

We recently demonstrated that natriuretic peptides and especially the atrial natriuretic peptide (ANP) are powerful lipolytic agents on isolated human fat cells. To search for a possible influence of obesity on ANP responsiveness, we compared the lipolytic effects of human ANP (h-ANP) on isolated subcutaneous abdominal adipose tissue (SCAAT) fat cells from young healthy lean and obese men. The lipid-mobilizing effects of an intravenous infusion of h-ANP was studied, as well as various metabolic and cardiovascular parameters that were compared in the same subjects. h-ANP (50 ng/min/kg) was infused iv for 60 min. Microdialysis probes were inserted in SCAAT to measure modifications of the extracellular glycerol concentrations during h-ANP infusion. Spectral analysis of blood pressure and heart rate oscillations that were recorded using digital photoplethysmography were used to assess changes in autonomic nervous system activity. h-ANP induced a marked and similar increase in glycerol and nonesterified fatty acids, and a weak increase in insulin plasma levels in lean and obese men. Plasma norepinephrine concentrations rose similarly during h-ANP infusion in lean and obese men. The effects of h-ANP infusion on the autonomic nervous system were similar in both groups, with an increase in the spectral energy of the low-frequency band of systolic blood pressure variability and a decrease in the spectral energy of the high-frequency band of heart rate. In SCAAT, h-ANP infusion increased extracellular glycerol concentration and decreased blood flow similarly in both groups. The increase in extracellular glycerol observed during h-ANP infusion was not modified when 0.1 mM propranolol was added to the microdialysis probe perfusate to prevent beta-adrenoceptor activation. These data show that ANP is a potent lipolytic hormone independent of the activation of the sympathetic nervous system, and that obesity did not modify the lipid-mobilizing effect of ANP in young obese subjects.
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PMID:The lipid-mobilizing effect of atrial natriuretic peptide is unrelated to sympathetic nervous system activation or obesity in young men. 1129 Aug 25

In the last several decades, the concept of "endocrinology" has been greatly changed. One major change was due to the discovery of peptide hormones secreted by the organs that were not "classical" endocrine organs. For example, corticotropin-releasing hormone and many neuropeptides are secreted by the neurons, atrial natriuretic peptide by the heart, endothelin-1 by the vascular endothelial cells, and leptin by the adipose tissues. Now, the brain, heart, vascular tissue and adipose tissue can be considered to be endocrine organs. Cardiovascular diseases and obesity are therefore important targets of the endocrine research. Adrenomedullin is a potent vasodilator peptide consisting of 52 amino acids. It was originally discovered from a human pheochromocytoma, and belongs to the calcitonin gene-related peptide (CGRP) family. Adrenomedullin is produced and secreted by various types of cells, for example, vascular endothelial and smooth muscle cells, cardiomyocytes, fibroblasts, macrophages, neurons, glial cells, and retinal pigment epithelial cells. Such ubiquitous expression has not been observed in other neuropeptides, including neuropeptide Y and CGRP. Expression of adrenomedullin is induced by hypoxia and proinflammatory cytokines. In addition to vasodilator actions, this peptide has central inhibitory actions on water drinking and salt appetite, effects on the secretion of some hormones and cytokines, inotropic actions and effects on cell growth and apoptosis. Adrenomedullin is produced by various non-endocrine tumors, as well as endocrine tumors, and acts as a growth stimulatory factor for the tumor cells. Adrenomedullin seems to be involved in the pathophysiology of many diseases, including ischemic heart diseases, inflammatory diseases, tumors, and even eye diseases. The adrenomedullin research implies that "the neuroendocrine system" exists in much broader types of cells than previously thought, and that the endocrine research is able to contribute to the understanding of the pathophysiology of many diseases.
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PMID:Adrenomedullin from a pheochromocytoma to the eye: implications of the adrenomedullin research for endocrinology in the 21st century. 1131 31

Assays for natriuretic peptides have received considerable attention as potential screening tests for congestive heart failure and left ventricular dysfunction. However, information regarding the impact of age, sex, and other physiologic characteristics on natriuretic peptide levels is limited. We examined a healthy reference sample of 911 subjects (mean age 55 years, 62% women) from the Framingham Heart Study who were free of hypertension, valvular disease, diabetes, atrial fibrillation, obesity, coronary heart disease, congestive heart failure, and renal failure, and who had normal left ventricular systolic function. Plasma brain natriuretic peptide and N-terminal atrial natriuretic peptide levels were measured, and multivariable regression used to assess correlates of natriuretic peptide levels. The strongest predictors of higher natriuretic peptide levels were older age and female sex. Other multivariable predictors included lower diastolic blood pressure (higher pulse pressure), lower body mass index, and higher left atrial size. Reference limits were then formulated based on the empirical distribution of natriuretic peptide levels by gender both across all ages and partitioned by age. Age-pooled reference limits compared with age-specific limits classified a higher proportion of healthy elderly subjects (17% vs 2.5%), but a lower proportion of healthy young subjects (1% vs 2.5%) as "abnormal." We conclude that interpretation of natriuretic peptide levels should take into consideration gender and possibly age. The reference limits derived from this large, healthy community-based sample will aid in the identification of elevated natriuretic peptide levels in clinical practice.
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PMID:Impact of age and sex on plasma natriuretic peptide levels in healthy adults. 1212 13

Little is known about essential hypertension in Hispanic Americans, despite the fact that they are the fastest-growing minority in the United States and have a disproportionate degree of hypertensive target organ damage. The authors studied 89 Caribbean Hispanic hypertensive patients who participated in six double-blind, randomized trials of antihypertensive agents. Demographics, laboratory data, sodium excretion, plasma renin activity, and atrial natriuretic peptide were obtained after 3-4 weeks on placebo. Blood pressure responses to angiotensin-converting enzyme (ACE) inhibitors, beta blockers, calcium channel blockers, hydrochlorothiazide (HCTZ), and fixed combinations of ACE inhibitors and HCTZ, were compared to the placebo values after 8-12 weeks of treatment. Patients had a multiple risk factor profile (obesity and diabetes) and a wide spectrum of blood pressure elevation, left ventricular hypertrophy, and hypertensive renal damage. Urine sodium excretion rates indicated inability to comply with salt restriction in 65% of patients. Plasma renin activity was lower than that of Hispanic normotensive controls, and 62% of patients had low-renin essential hypertension by renin profiling to sodium excretion. On analysis of variance, blood pressure reductions by calcium channel blockers, HCTZ, and ACE inhibitor/HCTZ combinations were significantly greater than that with placebo, while those of ACE inhibitors and beta blockers as monotherapy were not. The authors conclude that essential hypertension of Caribbean Hispanics is associated with multiple risk factors and is largely of the low-renin type. Responses to therapy are consistent with those observed in other populations with the low-renin phenotype and suggest salt-sensitivity of blood pressure in this population. Confirmation of the latter has implications for prevention and treatment of essential hypertension in Hispanics.
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PMID:Essential hypertension of Caribbean Hispanics: sodium, renin, and response to therapy. 1214 29

Endurance training increases natriuretic peptide synthesis in the hypertrophied myocardium of spontaneously hypertensive rats. We examined the effects of 22-week-long treadmill exercise on plasma and tissue atrial natriuretic peptide in Zucker rats, a model of genetic obesity and moderate hypertension without clear cardiac hypertrophy. The blood pressures of the animals were measured by the tail-cuff method, and plasma and tissue samples for the peptide determinations were taken at the end of the study. The training increased heart weight to body weight ratio, while atrial natriuretic peptide contents in the right and left atrium, ventricular tissue, and plasma did not change. The exercise prevented the elevation of blood pressure, which was observed in non-exercised obese Zucker rats, and also reduced blood pressure in the lean rats. In conclusion, these results suggest that in the absence of preceding myocardial hypertrophy, the long-term exercise-induced workload is not deleterious to the heart in experimental obesity, since no changes in plasma and tissue atrial natriuretic peptide were detected.
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PMID:Long-term physical exercise and atrial natriuretic peptide in obese Zucker rats. 1219 55

Plasma levels of aldosterone are not always predictable from the activity of renin and the concentration of potassium. Among the unexplained are elevated levels of aldosterone in some obese humans. Obesity is characterized by increased plasma fatty acids and oxidative stress. We postulated that oxidized fatty acids stimulate aldosteronogenesis. The most readily oxidized fatty acids are the polyunsaturated, and the most abundant of those is linoleic acid. We tested oxidized derivatives of linoleic acid for effects on rat adrenal cells. One derivative, 12,13-epoxy-9-keto-10(trans)-octadecenoic acid (EKODE), was particularly potent. EKODE stimulated aldosteronogenesis at concentrations from 0.5 to 5 micromol/L, and inhibited aldosteronogenesis at higher doses. EKODE's stimulatory effect was most prominent when angiotensin and potassium effects were submaximal. The lipid's mechanism of action was on the early pathway leading to pregnenolone; its action was inhibited by atrial natriuretic peptide. Plasma EKODE was measured by liquid chromatography/mass spectrometry. All human plasmas tested contained EKODE in concentrations ranging from 10(-9) to 5x10(-7) mol/L. In samples from 24 adults, levels of EKODE correlated directly with aldosterone (r=0.53, P=0.007). In the 12 blacks in that cohort, EKODE also correlated with body mass index and systolic pressure. Those other correlations were not seen in white subjects. The results suggest that oxidized derivatives of polyunsaturated fatty acids other than arachidonic are biologically active. Compounds like EKODE, derived from linoleic acid, may affect adrenal steroid production in humans and mediate some of the deleterious effects of obesity and oxidative stress, especially in blacks.
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PMID:Epoxy-keto derivative of linoleic acid stimulates aldosterone secretion. 1471 55

Hyperleptinemia may be involved in the pathogenesis of obesity-associated hypertension, however, the mechanism of hypertensive effect of leptin has not been elucidated. We investigated the effect of experimental hyperleptinemia on renal function, renal Na(+), K(+)-ATPase and ouabain-sensitive H(+), K(+)-ATPase activities in the rat. Leptin administered for 7 days (0.25 mg/kg twice daily sc) decreased food intake on 6th and 7th day of treatment but had no effect on body weight. Systolic blood pressure was 30.5% higher in leptin-treated animals. Urinary excretion of sodium decreased by 35.0% following leptin treatment. Leptin had no effect on potassium and phosphate excretion as well as on creatinine clearance. The activity of Na(+), K(+)-ATPase in the renal cortex and medulla was higher in leptin-treated rats by 32.4% and 84.2%, respectively. In contrast, leptin had no effect on either cortical or medullary ouabain-sensitive H(+), K(+)-ATPase. In pair-fed group, in which food intake was reduced to the level observed in leptin-treated group, no changes in sodium metabolism and renal Na(+), K(+)-ATPase were observed. Leptin decreased urinary excretion of nitric oxide metabolites by 55.0% and urinary excretion of cGMP by 26.3%. Plasma concentration of atrial natriuretic peptide tended to be higher and urinary excretion of urodilatin was 64.9% higher in leptin-treated animals. These data suggest that hyperleptinemia decreases natriuresis by up-regulating Na(+), K(+)-ATPase and stimulating tubular sodium reabsorption. This effect is mediated, at least in part, by deficiency of nitric oxide (NO). Abnormal renal sodium retention and vasoconstriction associated with NO deficiency may contribute to leptin-induced hypertension and to blood pressure elevation in hypertensive obese individuals.
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PMID:Up-regulation of renal Na+, K+-ATPase: the possible novel mechanism of leptin-induced hypertension. 1515 72

Essential hypertension is a heterogeneous disorder that is thought to develop because of several overlapping subsets of underlying mechanisms. One such causal pathway may involve pathophysiological alterations induced by obesity. In the present study, we examined whether investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, facilitates the search for its genes. Fifty-five extended families were selected on the basis of having > or =2 siblings affected by hypertension from a geographically remote French-Canadian population. Fifteen of these families showed a high prevalence (> or =70%) of obesity. Genome-wide scan using qualitative multipoint linkage analysis (GeneHunter 2.1; marker density <10 cM) was performed in the entire set of hypertensive families and the subset with high prevalence of obesity. In the scan involving all 55 families, the most significant loci (logarithm of odds [LOD] score=2.5) were identified on chromosomes 1 (D1S1597) and 11 (D11S1999). In the scan including only the subset of families with obesity-hypertension, the most significant locus (LOD score=3.1) was found on chromosome 1 in the same region as the scan involving all families (D1S1597). Genotyping additional markers increased the significance of this locus (LOD score=3.5) and refined its position (D1S2672). Several candidate genes of obesity-hypertension are located in close proximity; these include the tumor necrosis factor receptor 2 and atrial natriuretic peptide genes. These results suggest that investigating clinically defined subtypes of hypertension, such as obesity-associated hypertension, may facilitate the search for genes of this complex disorder.
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PMID:Genome-wide scan for linkage to obesity-associated hypertension in French Canadians. 1623 May 14


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