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

In essential hypertension, stroke and kidney damage may result from an impaired interaction of vasoregulatory systems. Stroke-prone spontaneously hypertensive rats (SHRSP) were studied to analyze the effects of a low-dose treatment of the angiotensin II type 1 receptor (AT1) blocker candesartan cilexetil on the expression of nitric oxide synthases (NOS) and on vascular structure. Both treated and untreated SHRSP were kept on a stroke-promoting dietary regimen, and compared with Wistar Kyoto rats (WKY). Early mortality of untreated SHRSP was prevented by the treatment. In untreated SHRSP, cerebral intraparenchymal vessels of the parietal lobe showed lesions of the vascular wall and its periphery, such as proteinaceous deposits, perivascular dilated spaces, increase in phagocytic cells, and decreased actin immunostaining. Renal lesions were more pronounced comprising arteriolar occlusion, extensive loss of actin, increased alpha1(IV) collagen expression, and glomerular sclerotic as well as tubulointerstitial lesions. Beneficial effects of the AT1 blockade were more pronounced in brain than in kidney. Activity profile of NOS showed increased NADPH diaphorase staining in media and endothelium of SHRSP; endothelial NOS3 immunoreactivity was decreased, but instead, inducible NOS2 increased in untreated SHRSP. These changes were largely prevented in the treated group. NOS activity in macula densa cells was unchanged, whereas afferent arteriolar renin levels were increased in untreated SHRSP. Results demonstrate an effective reduction of hypertensive vascular changes with a nonpressor dose of candesartan. A "role switch" of vascular NOS in hypertension from physiologic NOS3 toward deleterious NOS2 is suggested, and its prevention by the AT1 blocker points to an angiotensin II-dependent, nitric oxide-mediated pathway that may impair endothelial function and aggravate defects of the blood-brain barrier and kidney structures.
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PMID:Normalizing the expression of nitric oxide synthase by low-dose AT1 receptor antagonism parallels improved vascular morphology in hypertensive rats. 989 50

Essential hypertension is the leading preventable cause of death in the world. Epidemiological studies have shown that physical training can reduce blood pressure (BP), both in hypertensive and healthy individuals. Increasing evidence is emerging that DNA methylation is involved in alteration of the phenotype and of vascular function in response to environmental stimuli. We evaluated repetitive element and gene-specific DNA methylation in peripheral blood leukocytes of 68 volunteers, taken before (T0) and after (T1) a three-month intervention protocol of continuative aerobic physical exercise. DNA methylation was assessed by bisulfite-PCR and pyrosequencing. Comparing T0 and T1 measurements, we found an increase in oxygen consumption at peak of exercise (VO2peak) and a decrease in diastolic BP at rest. Exercise increased the levels of ALU and Long Interspersed Nuclear Element 1 (LINE-1) repetitive elements methylation, and of Endothelin-1 (EDN1), Inducible Nitric Oxide Synthase (NOS2), and Tumour Necrosis Factor Alpha (TNF) gene-specific methylation. VO2peak was positively associated with methylation of ALU, EDN1, NOS2, and TNF; systolic BP at rest was inversely associated with LINE-1, EDN1, and NOS2 methylation; diastolic BP was inversely associated with EDN1 and NOS2 methylation. Our findings suggest a possible role of DNA methylation for lowering systemic BP induced by the continuative aerobic physical training program.
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PMID:Effects of Physical Exercise on Endothelial Function and DNA Methylation. 3131 70

The risk of essential arterial hypertension was assessed in carriers of the NOS2 gene variants (rs1800482 (-954G>C), rs3730017 (C>T)). In subjects carrying C allele (rs1800482), the risk for essential arterial hypertension developing was higher by 1.7 times (OR=1.712, 95%CI 1.07-2.74), while the presence of T-allele (rs3730017) had a protective effect (OR=0.304, 95%CI 0.192-0.482). In patients with essential arterial hypertension, the presence of the C allele (rs1800482) was associated with a higher content of NO metabolites in the blood plasma. A positive correlation was found between the plasma content of nitrites and nitrates and the level of transcripts of VCAM1, ICAM1 genes in peripheral blood leukocytes. We found the influence of the C allele carriership on the expression VCAM1 and ICAM1 genes in patients with essential hypertension. It was hypothesized that this polymorphic site in the NOS2 gene can be involved in the development of endothelial dysfunction and essential arterial hypertension through modulation of NO level under condition of inflammation.
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PMID:The Role of Inducible NOS2 Gene Polymorphism in the Development of Essential Arterial Hypertension. 3176 80