Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five candidate genes including the lipoprotein lipase, leptin, leptin receptor, alpha-adducin and beta3 adrenergic receptor were selected to examine their possible contribution to essential hypertension (EH) in a Chinese population. On each side of the candidate gene loci, one to two highly polymorphic microsatellite markers were genotyped in 474 subjects recruited from 106 hypertension nuclear families in Shanghai. Both parametric and nonparametric linkage analyses were carried out using GENEHUNTER (version 2.0) after genotyping. Extended transmission disequilibrium testing (ETDT) was also conducted to detect preferential transmission of alleles to affected offspring. We failed to find the linkage between all these loci and EH by either parametric or nonparametric analysis, nor did we detect any significant transmission disequilibrium by ETDT. Our findings provide no support for a significant contribution of these five genes to the pathogenesis of EH among Shanghai people.
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PMID:Linkage analysis of five candidate genes and essential hypertension in 106 Chinese nuclear families. 1257 19

The prevalence of obesity is rising at an alarming rate worldwide, with consequent increases in type 2 diabetes, hypertension and cardiovascular morbidity and mortality. Central neural mechanisms, via the activation of the sympathetic nervous system may contribute to obesity-related cardiovascular diseases through the promotion of hypertension, dysrhythmia and atherosclerosis. However, the mechanisms responsible for this sympatho activation have not been identified. Leptin is an adipocyte-derived hormone that promotes weight loss by reducing appetite and by increasing energy expenditure through sympathetic stimulation to thermogenic tissue. Leptin also produces sympathoactivation to kidneys, hindlimb and adrenal glands, suggesting that the obesity-associated increase in sympathetic nerve activity could be due in part to these sympathetic effects of leptin. However, most human obesity appears to be associated with leptin resistance. Recent studies indicate that leptin resistance may be selective, with preservation of adverse sympathetic effects despite the loss of the metabolic actions of leptin. The leptin receptor is expressed in several hypothalamic nuclei including the arcuate nucleus. The melanocortin system, neuropeptide Y and corticotrophin-releasing factor have emerged as principal neuropeptide mediators of leptin action in the arcuate nucleus. These neuropeptides exert varying effects by different pathways. Several other candidate hypothalamic pathways that can mediate the effects of leptin have been identified. The understanding of neuronal signaling pathways involved in leptin signaling and energy balance has opened new research possibilities for the treatment of obesity.
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PMID:Leptin and the central neural mechanisms of obesity hypertension. 1258 70

Leptin acts in the hypothalamus to decrease appetite and increase sympathetic nerve activity. The leptin receptor is known to signal through the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway to modulate transcription of target genes. Alteration of the activity of phosphoinositol-3 kinase (PI3K) by leptin has also been reported, and inhibition of PI3K is known to block the leptin-induced suppression of feeding. We tested the hypothesis that leptin-induced renal sympathetic nerve activation is mediated by PI3K. We evaluated renal sympathetic nerve activity (RSNA) and feeding responses of C57BL/6J mice to intracerebroventricular (ICV) administration of leptin in the presence or absence of selective inhibitors of PI3K (LY294002 or wortmannin). As expected, ICV administration of leptin decreased food intake at 4 hours and 24 hours and increased RSNA. Pretreatment with the PI3K inhibitor LY294002 markedly attenuated both the decrease in food intake and the increase in RSNA induced by leptin. Wortmannin also inhibited the RSNA response to leptin. In contrast, PI3K inhibitors did not affect the RSNA response to MTII (melanocortin-3/4 receptor agonist). Our data demonstrate that PI3K appears to play an important role in the transduction of leptin-induced changes in renal sympathetic outflow.
Hypertension 2003 Mar
PMID:Intracellular mechanisms involved in leptin regulation of sympathetic outflow. 1262 93

Plasma leptin levels are elevated in obesity suggesting a pathophysiologic role of this hormone in obesity and related disorders, such as hypertension. Furthermore, despite excess leptin levels, leptin satiety action is blunted in obesity suggesting the occurrence of central leptin resistance. As leptin acts on the kidney to induce natriuresis, renal leptin receptor alterations could lead to a defect in sodium excretion and hence to hypertension. Therefore, the present study investigated renal leptin receptor (Ob-Ra and Ob-Rb) mRNA and leptin binding capacities in diet-induced hypertension. Feeding male, female, and testosterone-treated female rats a cafeteria diet for 10 weeks increased body fat mass, plasma insulin, and leptin levels. Furthermore, although male and testosterone-treated female cafeteria-fed rats were hypertensive, the female rats fed the same diet failed to develop elevated blood pressure. In renal medulla, Ob-Ra and Ob-Rb mRNA levels were unchanged after cafeteria diet feeding in all groups; however, binding analysis revealed Ob-R protein down-regulation exclusively in hypertensive rats. Moreover, renal Ob-R densities were inversely correlated to plasma leptin concentrations in male rats and testosterone-treated female rats but not in female rats. These findings demonstrate the existence of differences in renal Ob-R binding capacities, which are correlated to hypertension.
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PMID:Sexual dimorphism in cafeteria diet-induced hypertension is associated with gender-related difference in renal leptin receptor down-regulation. 1264 90

The metabolic syndrome in association with obesity is a major clinical problem inducing hypertension, diabetes mellitus, and atherosclerosis. Leptin induces angiogenesis by its proliferative effects on endothelial cells (ECs) via OB receptor (OB-Rb) gene. We evaluated the growth of ECs and intracellular signalings in response to leptin in vitro and the angiogenic effects of leptin in the cornea in vivo with and without adenovirus-mediated transfer of the OB-Rb gene in Zucker fatty (ZF) rats as a model for the metabolic syndrome. Recombinant adenovirus vector encoding rat OB-Rb (Ad.OB-Rb) or Escherichia coli. LacZ (Ad.LacZ) was transfected into cultured ECs from Zucker lean (ZL) rats and ZF rats. Leptin increased DNA synthesis dose-dependently in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb, but not with Ad.LacZ, improved the growth effects of leptin in ECs from ZF rats. Leptin induced phosphorylation of Janus kinase (JAK)2, signal transducer and activator of transcription (STAT)3, and extracellular signal-regulated kinase (ERK) in ECs from ZL rats but not ZF rats. Infection with Ad.OB-Rb restored phosphorylation of JAK2 and STAT3 in ECs from ZF rats. Leptin induced angiogenesis in cornea from ZL rats, but not from ZF rats. Coadministration of leptin and Ad.OB-Rb induced angiogenesis in cornea from ZF rats. Ad.LacZ did not influence the angiogenic effects of leptin. The impaired endothelial function with the leptin resistance may be one of causes of the atherosclerosis in the metabolic syndrome.
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PMID:Effects of leptin on endothelial function with OB-Rb gene transfer in Zucker fatty rats. 1292 73

1. We established a new animal model of metabolic syndrome, SHRSP fatty (fa/fa) rats, by crossing stroke-prone spontaneously hypertensive rats of the Izumo strain (SHRSP/Izm) to Zucker fatty (ZF) (fa/fa) rats. 2. The SHRSP fatty (fa/fa) rats have a missense mutation of the leptin receptor gene and plasma leptin concentrations are augmented. The SHRSP fatty (fa/fa) rats develop obesity and hypertension simultaneously. 3. Plasma metabolic parameters, including glucose, insulin and total cholesterol and triglyceride levels, were markedly elevated in SHRSP fatty (fa/fa) rats compared with SHRSP/Izm rats. Plasma triglyceride concentrations in SHRSP fatty (fa/fa) rats were significantly elevated compared with those in ZF (fa/fa) rats. The weight of adipose tissues in SHRSP fatty (fa/fa) rats was greater than that of SHRSP/Izm rats. The phenotype of SHRSP fatty (fa/fa) rats is similar to that of human metabolic syndrome.
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PMID:Establishment of a new animal model of metabolic syndrome: SHRSP fatty (fa/fa) rats. 1475 93

Obesity, from declining estrogen levels after menopause, increases the risk of heart disease, diabetes, and hypertension. Ovariectomy (OVX) in rats is a good model of estrogen insufficiency. The ensuing mild obesity is useful to study how hypoestrogenism alters adiposity. This study examines the hypothesis that in ovariectomized (OVX) rats modification of estrogen levels or treatment with a selective estrogen receptor modulator, raloxifene (RAL), alters leptinemia and modulates leptin receptor (Ob-R) abundance in hypothalamus and white adipose tissue, similar to the modification of adipose status induced by hypoestrogenism. Mid- and long-term studies (7 and 22 wk) were conducted to monitor the change in leptinemia in rats after estrogen loss by OVX and after estrogen replacement by 17beta-estradiol (OVX+E(2)) or RAL treatment (OVX+RAL). Leptin was significantly higher in OVX rats vs. controls, in a time-dependent manner. This effect was reversed by both E(2) and RAL treatment at 7 wk (P < 0.05) and 22 wk (P < 0.001). Moreover, E(2) or RAL treatment reversed the OVX-induced increases in food intake, body weight, and fat mass content; the modifications of serum parameters were examined to evaluate the different lipid profiles. We also evaluated Ob-R expression in hypothalamus and adipose tissue by Western blot analysis. The expression of the long functional isoform (Ob-Rb) increased at 7 wk only in adipose tissue and decreased at 22 wk in OVX rats in both tissues; these effects were reversed by E(2) or RAL treatment. We provide evidence that central and peripheral Ob-Rb expression is related to modification of estrogen levels.
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PMID:Estrogen and raloxifene modulate leptin and its receptor in hypothalamus and adipose tissue from ovariectomized rats. 1505 58

Vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) show the synthetic phenotype and exaggerated growth in comparison with VSMCs from normotensive Wistar-Kyoto (WKY) rats. We investigated genes associated with the synthetic phenotype and exaggerated growth of VSMCs from SHR by microarray. Expression of 1300 transcripts was evaluated by microarray with total mRNA extracted from mid-layer aortic smooth muscle of 3-week-old SHR/Izumo and WKY/Izumo rats. mRNAs encoding sodium-dependent neurotransmitter transporter, epidermal growth factor precursor, EEF2, leptin receptor long-isoform b, clathrin assembly protein short form, and preprocomplement 3 (pre-pro-C3) were expressed only in aortic smooth muscle from SHR by microarray and by reverse-transcription polymerase chain reaction analysis. Pre-pro-C3 mRNA was detected only in cultured VSMCs from SHR. Exogenous C3 changed VSMCs to the synthetic phenotype. Antisense oligodeoxynucleotides (ODN) to C3 reduced the higher level of DNA synthesis in VSMCs from SHR. Antisense ODN to C3 increased expression of SM22alpha mRNA and decreased expression of osteopontin and matrix Gla mRNAs. It also decreased expression of growth factor mRNAs in VSMCs from SHR. In conclusion, we have shown that C3, independent of other complement molecules, has direct effects on the phenotype of VSMCs and stimulates growth of these cells. C3 is produced only by VSMCs from SHR. Therefore, C3 may be the gene underlying the synthetic phenotype and exaggerated growth of VSMCs from SHR. C3 may be a new target for the treatment of hypertension.
Hypertension 2004 Jul
PMID:Complement 3 is involved in the synthetic phenotype and exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats. 1512 74

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

Since non-alchoholic steatohepatitis (NASH) is often accompanied with metabolic syndrome comprising obesity, type-2 diabetes and hypertension, it is hypothesized that adipocytokines, insulin resistance and autonomic nervous system play crucial roles in disease progression of NASH. On the other hand, hepatic stellate cells (HSCs) have been shown to produce leptin when they get activated during hepatic fibrogenesis. Therefore, we investigated the role of leptin in fibrogenesis in the liver. Xenobiotics-induced liver fibrosis was extremely diminished in ob/ob mice and Zucker (fa/fa) rats, an inborn leptin- and leptin receptor (Ob-R)-deficient animal, respectively. Further, leptin increased transforming growth factor (TGF)-beta mRNA in isolated sinusoidal endothelial cells and Kupffer cells, suggesting that leptin promotes hepatic fibrogenesis through up-regulation of TGF-beta in the liver. Moreover, leptin augmented PDGF-dependent proliferation of HSCs by enhancing downstream intracellular signaling pathways via mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/Akt. Taken together, it is postulated that leptin acts as a profibrogenic cytokine in sinusoidal microenvironment. These findings indicate that leptin is one of the key regulators for inflammation and progression of fibrosis in various chronic liver diseases including NASH.
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PMID:The role of leptin in progression of non-alcoholic fatty liver disease. 1619 23


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