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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The obese gene product, leptin, plays a central role in food intake and energy metabolism. The physiological roles of leptin in human bodily function have been broadened over the past decade since leptin was first discovered in 1994. Evidence has suggested that leptin plays a specific role in the intricate cascade of cardiovascular events, in addition to its well-established metabolic effects. Leptin, a hormone linking adiposity and central nervous circuits to reduce appetite and enhance energy expenditure, has been shown to increase overall sympathetic nerve activity, facilitate glucose utilization and improve insulin sensitivity. In addition, leptin is capable of regulating cardiac and vascular contractility through a local nitric oxide-dependent mechanism. However, elevated plasma leptin levels or hyperleptinemia, have been demonstrated to correlate with hyperphagia, insulin resistance and other markers of the metabolic syndrome including obesity, hyperlipidemia and hypertension, independent of total adiposity. Elevated plasma leptin levels may be an independent risk factor for the development of cardiovascular disease. Although mechanisms leading to hyperleptinemia have not been well described, factors such as increased food intake and insulin resistance have been shown to rapidly enhance plasma leptin levels and subsequently tissue leptin resistance. These findings have prompted the speculation that leptin in the physiological range may serve as a physiological regulator of cardiovascular function whereas elevated plasma leptin levels may act as a pathophysiological trigger and/or marker for cardiovascular diseases due to tissue leptin resistance.
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PMID:Leptin and hyperleptinemia - from friend to foe for cardiovascular function. 1507 62

Although excess hypothalamic agouti-related peptide (AGRP), an endogenous antagonist of the melanocortin 3/4 receptor, causes hyperphagia and obesity, its role in regulating cardiovascular function is unclear. This study examined control of mean arterial pressure (MAP), heart rate (HR), and metabolism during chronic central administration of AGRP in rats. A cannula was placed in the lateral ventricle for intracerebroventricular infusion, and arterial and venous catheters were implanted for monitoring MAP and HR 24 hours per day, as well as intravenous infusions. After a 5-day control period, rats received AGRP (n=6; 0.02 nmol per hour ICV) or artificial cerebrospinal fluid (aCSF; n=9; 0.02 nmol per hour ICV) for 12 days, followed by a 5-day recovery period. A third group was infused intracerebroventricularly with AGRP and pair-fed to match food intake of control rats (n=7). AGRP produced a peak decrease in MAP and HR of -7+/-2 mm Hg and -68+/-7 bpm, respectively, despite increased food intake (from 23+/-0.5 to 36+/-3 g per day) and weight gain (from 350+/-8 to 454+/-5 g). AGRP also increased glomerular filtration rate, plasma insulin, glucose, and leptin. AGRP infusion in pair-fed rats produced a peak decrease in HR of -70+/-8 bpm but did not alter MAP or other variables. The metabolic effects of AGRP may be secondary to hyperphagia because they were abolished in pair-fed rats. aCSF infusion did not change any of the variables studied. These results demonstrate that increased central nervous system AGRP levels produce chronic reductions in MAP and HR despite marked increases in food intake and weight gain that normally tend to raise arterial pressure.
Hypertension 2004 Dec
PMID:Cardiovascular, renal, and metabolic responses to chronic central administration of agouti-related peptide. 1554 13

The adipose-derived hormone leptin was first described as a satiety factor, but recent studies have demonstrated that leptin acts on various physiologic processes and plays an important role in obesity and the associated hypertension. In this article, we review recent data on leptin signaling as it relates to nutrition. Plasma leptin levels are positively correlated to body fat and adipocyte size and, therefore, levels are higher during obesity. The hyperphagia in the presence of hyperleptinemia in obesity is a paradoxical effect. Leptin signaling primarily depends on the leptin receptor (Ob-R). The suppressor of cytokine-signaling (SOCS) protein, in particular SOCS-3, was shown as a leptin-regulated inhibitor of proximal leptin signaling, although its role during obesity remains uncertain.
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PMID:Nutritional regulation of leptin signaling. 1568 81

The various mechanisms that may explain the association between brain dysfunction and the pathogenesis of metabolic syndrome (MS) leading to cardiovascular disease and type 2 diabetes have been reviewed. A Medline search was conducted until September 2003, and articles published in various national and international journals were reviewed. Experts working in the field were also consulted. Compelling evidence was found that saturated and total fat and low dietary n-3 fatty acids and other long-chain polyunsaturated fatty acids (PUFAs) in conjunction with sedentary behavior and mental stress combined with various personality traits can enhance sympathetic activity and increase the secretion of catecholamine, cortisol and serotonin, all of which appear to be underlying mechanisms involved in MS. Excess secretion of these neurotransmitters in conjunction with underlying long-chain PUFA deficiency may damage the neurons in the ventromedial hypothalamus and insulin receptors in the brain, in particular during fetal life, infancy and childhood, and lead to their dysfunction. Since 30-50% of the fatty acids in the brain are long-chain PUFAs, especially omega-3 fatty acids which are incorporated in the cell membrane phospholipids, it is possible that their supplementation may have a protective effect. Omega-3 fatty acids are also known to enhance parasympathetic activity and to increase the secretion of anti-inflammatory cytokines as well as acetylecholine in the hippocampus. It is possible that a marginal deficiency of long-chain PUFAs, especially n-3 fatty acids, due to poor dietary intake during the critical period of brain growth and development in the fetus, and later in the infant and also possibly in the child, adolescent and adult may enhance the release of tumor necrosis factor-alpha (TNF-alpha) interleukin (IL)-1, 2 and 6 and cause neuronal dysfunction. Experimental studies indicate that ventromedial hypothalamic lesions in rats induce hyperphagia, resulting in glucose intolerance and insulin resistance. Treatment with neuropeptide Y abolished hyperphagia and ob mRNA (leptin mRNA) in this animal model. Long-term infusion of norepinephrine and serotonin into the ventromedial hypothalamus impaired pancreatic islet function inasmuch as ventromedial hypothalamic norepinephrine and serotonin levels were elevated in hyperinsulinemic and insulin-resistant animals. Treatment with insulin was associated with restoration of hypothalamic neurotransmitter abnormalities, indicating that ventromedial hypothalamus dysfunction can impair pancreatic beta cells resulting in metabolic abnormalities consistent with MS. Treatment with omega-3 fatty acids, beta blockers, ACE inhibitors, estrogen, and meditation may have a beneficial effect on insulin receptors and ventromedial hypothalamic dysfunction. However, no definite or precise insight into the pathophysiological link between MS, brain function and nutrition is available. Despite this, epidemiological studies and intervention trials indicate that treatment with n-3 fatty acids may be adopted in clinical practice and used to direct therapy for prevention of type 2 diabetes, hypertension, coronary artery disease (CAD), and atherosclerosis, thereby indicating that MS may also respond to this treatment.
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PMID:Can brain dysfunction be a predisposing factor for metabolic syndrome? 1575 41

McKusick-Kaufman syndrome (MKS) is an autosomal recessive disorder characterized by post-axial polydactyly, congenital heart defects and hydrometrocolpos, a congenital structural abnormality of female genitalia. Mutations in the MKKS gene have also been shown to cause some cases of Bardet-Biedl syndrome (BBS) which is characterized by obesity, pigmentary retinopathy, polydactyly, renal abnormalities and hypogenitalism with secondary features of hypertension and diabetes. Although there is overlap in clinical features between MKS and BBS, MKS patients are not obese and do not develop retinopathy or have learning disabilities. To further explore the pathophysiology of BBS and the related disorder MKS, we have developed an Mkks(-/-) mouse model. This model shows that the absence of Mkks leads to retinal degeneration through apoptosis, failure of spermatozoa flagella formation, elevated blood pressure and obesity. The obesity is associated with hyperphagia and decreased activity. In addition, neurological screening reveals deficits in olfaction and social dominance. The mice do not have polydactyly or vaginal abnormalities. The phenotype of the Mkks(-/-) mice closely resembles the phenotype of other mouse models of BBS (Bbs2(-/-) and Bbs4(-/-)). These observations suggest that the complete absence of MKKS leads to BBS while the MKS phenotype is likely to be due to specific mutations.
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PMID:Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome. 1577 95

The connection of gout and hyperuricaemia with gluttony, overindulgence in food and alcohol and obesity dates from ancient times. Studies from different parts of the world suggest that the incidence and severity of hyperuricaemia and gout may be increasing. Uric acid (urate) is the end product of purine degradation. Although most uric acid is derived from the metabolism of endogenous purine, eating foods rich in purines contributes to the total pool of uric acid. Sustained hyperuricaemia is a risk factor for acute gouty arthritis, chronic tophaceous gout, renal stones and possibly cardiovascular events and mortality. Before starting lifelong urate-lowering drug therapy, it is important to identify and treat underlying disorders that may be contributing to hyperuricaemia. It is relevant to recognize the strong association of the insulin resistance syndrome (IRS) (abdominal obesity, dyslipidaemia, hypertension, raised serum insulin levels and glucose intolerance) with hyperuricaemia. Consumption of meat, seafood and alcoholic beverages in moderation and attention to food portion size is important. Moderation in the consumption of not only beer but also other forms of alcohol is essential. In the obese, controlled weight management has the potential to lower serum urate in a quantitatively similar way to relatively unpalatable "low purine" diets. Non-fat milk and low-fat yogurt have a variety of health benefits and dairy products may have clinically meaningful antihyperuricaemic effects. In addition, fruits, such as cherries and high intakes of vegetable protein diet may reduce serum urate levels.
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PMID:Dietary factors and hyperuricaemia. 1637 34

A sedentary lifestyle, in conjunction with excessive food intake, is contributing to the worldwide increasing prevalence of obesity. Overeating is associated with insulin resistance, hypertension, dyslipoproteinaemia and endothelial dysfunction. A complicated network of cellular mechanisms has recently been suggested to play a central role in the control of energy homeostasis and metabolic response to overfeeding in animals. Understanding these mechanisms will substantially increase our knowledge about the physiological and biochemical factors leading to obesity and insulin resistance in humans.
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PMID:[Metabolic consequences of overeating]. 1640 47

Our simple definition of ethics is good thought, speak and action. Epistemology means the hypothesis of facts about thought, speech and action. Medical practice is all means of medicine. Medicine classifies people into normal and abnormal. The abnormal are the sick. They loose some organs or those normal looking organs are dysfunctional. They are social problems, some can be treated, and some do not get the appropriate care. The problems of society of normal people are overeating and obesity, abortion, drug abuse, promiscuity, torture, terrorism, disobeying rules and order, corruption, brain-washing and unethical advertisements, etc. On the other hand, the social problems of the abnormal are down, deafness, blindness, dumb, hypertension, hypercholesterolemia, diabetes mellitus and cancer, etc. An example of the social-doctor problem is the mal distribution of doctors in rural areas. It was reported by the ministry of public health that the ratio of doctor to population to be 1:800 in Bangkok and 1:5, 700 in some rural areas in the north eastern part of Thailand. The doctors, themselves, are at a high grade of worker and intelligent quotient. They know all the problem and, at the same time, create problems, both, faster than the general population can do. It affects good and bad in the society. In the past, present and the foreseeable future the medical students get their studies in the western style. Their medical schools are situated in big cities. These schools are old and famous. They learn their medical procedure in a big hospital of more than 400 beds in the inpatient department wards. Their instructors and professors are highly qualified, are middle class people and well accepted in the society. Their families are lovely and warm. Their children study in the first class schools in town. The medical students feel very happy and appreciate seeing their professors in television routinely at prime time. In conclusion, their professors are an example of role model for them to follow. Everyone looks for security in her/his profession. Facts need no proof and reference. People with justice in mind should believe and understand the above mentioned. This leads to the problem of mal distribution of doctors in rural areas, why do doctors live in big cities or wish to be in the private sector? In fact, not many a number of doctors serve in the rural area. About 4-5 of them, their name will be announced yearly as the best rural doctor award. After the big ceremony, lasted not longer than a month, it is hard to remember their name. They are proud to be praised, it pushes them into stress intentionally with all the best of their intelligence and the total of their body strength to work harder in rural. Unfortunately their earning, the security of their profession, the increased chance of being sued, to get caught in the medical litigation, the expenses of their family social status and the study of their children cannot be compared to of those doctors in big city and/or in the private sector. Mal distribution of doctors in remote rural areas has been a persisting unresolved problem in many parts of the world, why not apply the principles of ethics and epistemology? They have been left, untouched forever.
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PMID:Ethics and the comprehensive application of epistemology in medical practice. 1651 4

The metabolic syndrome (MS) is a cluster of metabolic abnormalities with insulin resistance as a major characteristic. The main adverse consequence of the MS is cardiovascular disease (CVD). Complex, mutually reinforcing interactions between obesity and insulin resistance largely account for the pathogenesis of MS. Central pathophysiologic features include: insulin resistance, atherogenic dyslipidemia, chiefly present as low HDL-C together with increases in triglycerides and small dense, low density lipoprotein particles, hypertension, a proinflammatory state, with increases in acute-phase reactants, and a prothrombotic state. Although lifestyle and overeating seem to be the triggering pathogenic factors, genetic elements are also involved in the pathogenesis of MS. When present, insulin resistance results in impaired insulin action in insulin-sensitive tissues such as muscle, fat, and liver. Insulin resistance results in abnormalities of glucose metabolism, with reduced peripheral disposal of glucose in muscle and increased hepatic glucose output in the fasting state. But, most importantly, the progressively increasing concentration in circulating glucose leads to various abnormalities in insulin secretion. Elevated insulin levels themselves are atherogenic by inducing an oxidative stress and by stimulating sympathetic-nerve activity. Ectopic fat deposition, stress, proinflammatory state, and a maladaptive response of innate immunity may together concur to the development of the MS. When this condition is acknowledged, substantial modification of life style and correction of each single risk factor should be pursued without uncertainties and without hierarchical approach; this means that each risk factor should be treated and brought to target.
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PMID:Insulin resistance: trigger or concomitant factor in the metabolic syndrome. 1663 26

The increased prevalence of obesity in Western society has been well established for many years, and with this trend, the prevalence of other associated pathologies including insulin resistance, dyslipidaemia, hypertension and the genesis of a proinflammatory and prothrombotic environment within individuals is also rapidly increasing, resulting in a condition known as the~metabolic syndrome. From a physiological perspective, one of the most severe consequences of the metabolic syndrome is a progressive inability of the cardiovascular system to adequately perfuse tissues and organs during either elevated metabolic demand and, if sufficiently severe, under basal levels of demand. For the study of the metabolic syndrome, the OZR (obese Zucker rat) represents an important tool in this effort, as the metabolic syndrome in these animals results from a chronic hyperphagia, and thus can be an excellent representation of the human condition. As in afflicted humans, OZR experience an attenuated functional and reactive hyperaemia, and can ultimately experience an ischaemic condition in their skeletal muscles at rest. The source of this progressive ischaemia appears to lie at multiple sites, as endothelium-dependent vasodilator responses are strongly impaired in OZR, and specific constrictor processes (e.g. adrenergic tone) may be enhanced. Whilst these active processes may contribute to a reduction in blood flow under resting conditions or with mild elevations in metabolic demand, an evolving structural alteration to individual microvessels (reduced distensibility) and microvascular networks (reduced microvessel density) also develop and may act to constrain perfusion at higher levels of metabolic demand. Given that constrained muscle perfusion in the metabolic syndrome appears to reflect a highly integrated, multi-faceted effect in OZR, and probably in humans as well, therapeutic interventions must be designed to address each of these contributing elements.
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PMID:Vascular function in the metabolic syndrome and the effects on skeletal muscle perfusion: lessons from the obese Zucker rat. 1714 86


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