Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, the relationship between hypertension and abnormal carbohydrate metabolism is explored. A review of the current literature reveals that people with hypertension are also likely to suffer from insulin resistance, glucose intolerance, and hyperinsulinemia. Likewise, hypertension is prevalent in obese and diabetic patients. Deficiency of insulin at the cellular level may be a common mechanism in the development of hypertension in patients with type I or type II diabetes mellitus. Essential hypertension appears to be an insulin-resistant state. Insulin resistance may engender hypertension by increasing peripheral vascular resistance as well as by increasing salt retention at the level of the kidney. Therefore effective antihypertensive therapy should include agents that do not adversely affect carbohydrate metabolic abnormalities. Commonly used antihypertensive agents, such as thiazide, thiazide-like diuretics, and beta-blockers, are associated with glucose intolerance and increased insulin resistance. In contrast, angiotensin-converting enzyme inhibitors, calcium antagonists, and peripheral alpha-blockers (such as prazosin and terazosin) do not adversely affect glucose tolerance or insulin sensitivity. In addition, alpha-blockers have a positive effect on the serum lipid profile. The entire multifactorial cardiac risk profile must be considered when choosing therapeutic agents for conditions that have an impact on cardiovascular disease.
 ...
PMID:Is hypertension an insulin-resistant state? Metabolic changes associated with hypertension and antihypertensive therapy. 187 73

Platelet-activating factor (PAF) acetylhydrolase is an enzyme that inactivates PAF. Deficiency of this enzyme is caused by a missense mutation in the gene. We previously found a higher prevalence of this mutation in patients with ischemic stroke. This fact suggests that the mutation might enhance the risk for stroke through its association with hypertension. We have addressed this hypothesis by analyzing the prevalence of the mutation in hypertension. We studied 138 patients with essential hypertension, 99 patients with brain hemorrhage, and 270 healthy controls. Genomic DNA was analyzed for the mutant allele by the polymerase-chain reaction. The prevalence of the mutation was 29.3% (27.4% heterozygotes and 1.9% homozygotes) in controls and 36.2% in hypertensives and the difference was not significant. The prevalence in patients with brain hemorrhage was significantly higher than the control: 32.6% heterozygotes and 6.1% homozygotes (p <0.05). PAF acetylhydrolase deficiency may be a genetic risk factor for vascular diseases.
 ...
PMID:A mutation in plasma platelet-activating factor acetylhydrolase (Val279Phe) is a genetic risk factor for cerebral hemorrhage but not for hypertension. 975 12

The so-called essential hypertension is not a single entity but a mixed bag with several polygenic quantitative traits acting in concert in different combinations in different individuals. This review collates all published information from different centres using different approaches to identify candidate genes in human hypertension. 1) gene targeting approach in animal models of HT (Smithies and Maeda, 1995); 2) identification of 874 candidate SNPs in 75 candidate genes for human HT (Halushka et al, 1999); 3) comparative genomic approach translating QTLs between rat and human HT, to identify 26 chromosome regions on 16 autosomes (Stoll M et al, 2000); 4) Ten centimorgan genome-wide scan done on 2010 affected sibling pairs drawn from 1599 severely hypertensive families (Caulfield et al, 2003). The molecular mechanisms of various molecules involved in the homeostasis of blood pressure are discussed. NO, O2, PG12, EDHF, endothelin, IL-6, selectin, phospholipase A2G1B, BH4, SOD, IRS-1, adrenomedullin, PAMP, CGRP, ANP, bradykinin and bombesin; adducin alpha, beta, gamma, SAH, renin, angiotensinogen. angiotensin II, aldosterone CYP11B1, mineralocorticoid receptors, 11betaHSD, DBH, PNMT, beta2adrenoreceptors, and genes related to ion transport-sodium-lithium cotransporters, ENaC, NaCl cotransporters NKCC2, KCNJ and NaKATPase. Altered gene expression in fetus due to maternal malnutrition also "programmes" for adult hypertension.
 ...
PMID:Hypertension: molecular approach. 1563 21

It has been proposed that "nephron underdosing," i.e., a low number of nephrons at the time of birth, is linked to essential hypertension and a greater propensity to develop progressive loss of renal function after renal injury. This hypothesis was confirmed recently by examining the number of glomeruli in patients with essential hypertension. The mechanisms through which a low number of nephrons causes hypertension have not been clarified, but it is likely that functional changes in postglomerular segments of the nephron, e.g., handling of sodium, play an important role. Neonatal uninephrectomy increases BP, renders BP salt sensitive, and renders the kidney more susceptible to damage. Apart from genetic factors, fetal/maternal malnutrition during pregnancy seems to play an important role in the pathogenesis of nephron underdosing. Furthermore, intrauterine programming during organogenesis, e.g., by hyperglycemia, seems to be important: In animal experiments, offspring of either hyperglycemic or diabetic mothers have fewer nephrons.
 ...
PMID:Nephron number and renal risk in hypertension and diabetes. 1593 29

Evidence is reviewed supporting the presence of an inherited structural defect in the plasma membranes of somatic cells of humans who have type 2 diabetes mellitus and sodium-sensitive essential hypertension. This magnesium-binding defect (MgBD) consists of a decreased content of tightly bound Mg2+ ion in the cell membrane and limits the amount of Mg2+ that enters the cell, some of which combines with ATP4-, produced by the cell, to form MgATP2-, the currency of metabolic energy. Consequently, in both prediabetes and overt diabetes, the intracellular concentration of the interdependent Mg2+ and MgATP2- ions is significantly less than normal. These 2 ions are required as cofactors and (or) substrates for some 300 enzyme systems in human metabolism, many of which are involved with insulin. Thus the decreased activities of particular ones of these enzyme systems due to the decreased intracellular [Mg2+] and its dependent [MgATP2-] are responsible for (i) insulin resistance and (ii) decreased insulin secretion and (or) production, the 2 pathophysiological processes required for the occurrence of type 2 diabetes mellitus. These 2 processes can account for all of the morbid symptoms associated with this disease. Thus, the decreased intracellular concentration of the interdependent Mg2+ and MgATP2- ions constitutes the etiology of genetic predisposition to type 2 diabetes mellitus and can be corrected by 2 identified peptide Mg2+-binding promoters that are derived from the carboxyl terminal of the tachykinin substance P and occur in normal blood plasma. Decreased intracellular [Mg2+] and [MgATP2-] can also result from a dietary deficiency of magnesium or from an abnormal accumulation of saturated fatty acids in cell membranes, which inhibits the entrance of Mg2+ into the cell; thus it is also the etiology not only of diabetes caused by magnesium deficiency, but also of the "lipotoxic" type 2 diabetes mellitus. Although these pathologies cannot be corrected by the Mg2+-binding promoters, they can be corrected, respectively, by dietary magnesium supplementation or by exercise plus dietary caloric and lipid restriction. Theoretically, the disease syndrome containing type 2 diabetes mellitus may involve approximately 30% of the population.
 ...
PMID:Evidence that the etiology of the syndrome containing type 2 diabetes mellitus results from abnormal magnesium metabolism. 1841 43

Platelet-activating factor (PAF) is a phospholipid mediator with a wide range of potent biological activities. The molecular structure of PAF is identified as 1-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine and it is degraded by the enzyme PAF acetylhydrolase (PAF-AH), which removes the sn-2 acetyl moiety of the molecule. Plasma PAF-AH activity is elevated in various disorders, including stroke, and this is considered an adaptation to the enhanced inflammatory or thrombotic processes in such disorders. Deficiency of plasma PAF-AH occurs due to a missense mutation (G994-->C) in exon 9 of the PAF-AH gene, which results in a Val-->Phe substitution at position 279 of the mature enzyme protein. This mutation is found in about 4% of the general Japanese population. However, it is not specifically related to any particular disease. The prevalence of plasma PAF-AH deficiency and the frequency of mutant alleles are significantly higher in patients suffering from stroke as compared to healthy controls. The prevalence of the mutation was similar in the groups of patients with atherothrombotic infarction and intracerebral hemorrhage. There was no difference in the prevalence of the mutation in the patients with essential hypertension as compared to that in healthy in controls. Therefore plasma PAF-AH deficiency may be considered as a genetic risk factor for stroke, and recognition of this mutation in individuals may be useful for early initiation of preventive measures against stroke.
 ...
PMID:[Plasma platelet-activating factor acetylhydrolase (PAF-AH) deficiency as a risk factor for stroke]. 1906 65

We tested the hypothesis that meat is a source of peptides that are effective at preventing and reducing chronic lifestyle-related diseases (CLSRDs) such as hypertension. This analysis reflects the importance of empowering hypertensive people in quality versus quantity of life issues, and in offering nutritional treatment options rather than medical alternatives. For both hypertensive and normotensive individuals, chemically based medications may have harmful side effects. Functional food rich in antioxidant vitamins, and proteins or biologically active peptides, can lower blood pressure in persons with essential hypertension, possibly by preventing an underlying cause of the condition. Deficiency in consumption of crucial nutrients such as proteins from meat origins, along with abnormalities in carbohydrate and fat metabolism, may underlie the etiology of the clinical course of hypertension. Food derived from meat rich in nutrients may provide physiologically functional peptides, as well as improve digestion, and the metabolism of carbohydrate and fats, thus lowering blood pressure, and normalizing associated biochemical and histopathological changes. Meat was found to have value, because proteolysis of meat muscle generated a substantial number of multi-amino acid peptides that have nutrafunctional roles, and some of which have strong angiotension-converting enzyme inhibitory activity. This also demonstrates that meat proteins might lead to better nutraceutical therapy that minimizes health problems, and might aid in finding the most effective approaches for meeting the needs of all hypertension patients.
 ...
PMID:A review of meat protein hydrolysates and hypertension. 2055 23

During the last 10 years, a series of exciting observations has led to a new theory of pathophysiology using insights from evolutionary biology and neuroendocrine immunology to understand the sequelae of chronic inflammatory disease. According to this theory, disease sequelae can be explained based on redirection of energy-rich fuels from storage organs to the activated immune system. These disease sequelae are highly diverse and include the following: sickness behavior, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, increase of adipose tissue near inflamed tissue, alterations of steroid hormone axes, elevated sympathetic tone and local sympathetic nerve fiber loss, decreased parasympathetic tone, hypertension, inflammation-related anemia, and osteopenia. Since these disease sequelae can be found in many animal models of chronic inflammatory diseases with mammals (e.g., monkeys, mice, rats, rabbits, etc.), the evolutionary time line goes back at least 70 million years. While the initial version of this theory could explain prominent sequelae of chronic inflammatory disease, it did not however address two features important in the pathogenesis of immune-mediated diseases: the time point when an acute inflammatory disease becomes chronic, and the appearance of hypertension in chronic inflammation. To address these aspects more specifically, a new version of the theory has been developed. This version defines more precisely the moment of transition from acute inflammatory disease to chronic inflammatory disease as a time in which energy stores become empty (complete energy consumption). Depending on the amount of stored energy, this time point can be calculated to be 19-43 days. Second, the revised theory addresses the mechanisms of essential hypertension since, on the basis of water loss, acute inflammatory diseases can stimulate water retention using a positively selected water retention system (identical to the energy provision system). In chronic smoldering inflammation, however, there is no increased water loss. In contrast, there is increased water generation in inflamed tissue and inflammatory cells, and the activation of the water retention system persists. This combination leads to a net increase of the systemic fluid volume, which is hypothesized to be the basis of essential hypertension (prevalence in adults 22-32%).
 ...
PMID:Evolutionary medicine and chronic inflammatory state--known and new concepts in pathophysiology. 2227 Nov 69

Hugh de Wardener died on 29th September 2013, ten days before his 98th birthday. He had a diverse upbringing and qualified in Medicine in 1939. He joined the army but was captured in 1942 and imprisoned in Singapore and Thailand until 1945. His clinical care of fellow prisoners was highly regarded. He preserved their clinical records and used them, post-war, to write two Lancet papers. One showed, for the first time, that Wernickes encephalopathy could be caused by severe malnutrition and cured by small doses of vitamin B1. His later academic interests were based on the emphasis he placed on renal physiology. This applied to the topic most associated with his name-Natriuretic Hormone. Whilst de Wardener never isolated this hormone, his early experiments, demonstrating that a third factor other than GFR and aldosterone affected renal sodium transport, were substantiated by others. Hugh had many research interests: pyelonephritis, renal histology, maintenance dialysis and metabolic/renal bone disease. In his later years he researched intensively into the role of sodium and salt in the aetiology of essential hypertension. Hugh was president of the International Society of Nephrology (1969-72) and the UK Renal Association (1975-78). He received many awards and recognitions from across the world, many of them after his (so-called) retirement. Throughout his career he never neglected the care of his patients. As Bob Schrier wrote in his obituary of de Wardener in Kidney International he was a caring physicianwhose dedication to his patients welfare was exemplary.
...
PMID:Hugh de Wardener - the Man and the Scientist. 2691 74

The rising prevalence of primary pediatric hypertension and its tracking into adult hypertension point to the importance of determining its pathogenesis to gain insights into its current and emerging management. Considering that the intricate control of BP is governed by a myriad of anatomical, molecular biological, biochemical, and physiological systems, multiple genes are likely to influence an individual's BP and susceptibility to develop hypertension. The long-term regulation of BP rests on renal and non-renal mechanisms. One renal mechanism relates to sodium transport. The impaired renal sodium handling in primary hypertension and salt sensitivity may be caused by aberrant counter-regulatory natriuretic and anti-natriuretic pathways. The sympathetic nervous and renin-angiotensin-aldosterone systems are examples of antinatriuretic pathways. An important counter-regulatory natriuretic pathway is afforded by the renal autocrine/paracrine dopamine system, aberrations of which are involved in the pathogenesis of hypertension, including that associated with obesity. We present updates on the complex interactions of these two systems with dietary salt intake in relation to obesity, insulin resistance, inflammation, and oxidative stress. We review how insults during pregnancy such as maternal and paternal malnutrition, glucocorticoid exposure, infection, placental insufficiency, and treatments during the neonatal period have long-lasting effects in the regulation of renal function and BP. Moreover, these effects have sex differences. There is a need for early diagnosis, frequent monitoring, and timely management due to increasing evidence of premature target organ damage. Large controlled studies are needed to evaluate the long-term consequences of the treatment of elevated BP during childhood, especially to establish the validity of the current definition and treatment of pediatric hypertension.
 ...
PMID:Primary Pediatric Hypertension: Current Understanding and Emerging Concepts. 2878 Jun 27


1