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)

The discovery of at least 29 genes encoding putative guanylyl cyclases in Caenorhabditis elegans has raised the question as to whether there are numerous receptors yet to be discovered in the mammal. The nematode, however, not only seems ideal to study guanylyl cyclase receptor localization and function, given the large variety of isoforms, but also leads to possible identification of ligands for orphan guanylyl cyclases by the use of genetic and behavioral assays. A recent powerful approach to describe the function of different guanylyl cyclase isoforms in mammals has been the disruption of the corresponding genes in the mouse. A salt resistant elevation of blood pressure, which corresponds to the phenotype of 50% of all human patients with essential hypertension, is observed in mice lacking the GC-A-receptor. Mice missing the GC-C receptor have been shown to be resistant to STa, an E. coli heat-stable enterotoxin, which is largely responsible for travellers diarrhea in adults and mortality due to diarrhea in infants.
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PMID:New insights on the functions of the guanylyl cyclase receptors. 924 17

Natriuretic peptide system plays a well-defined role in the regulation of blood pressure and fluid volume. Although the effects of natriuretic peptides (atrial natriuretic peptide, brain natriuretic peptide and C-type natriuretic peptide) are mediated by specific biologic receptors, their plasma level is influenced by clearance receptors. It has been demonstrated that in hypertensive subjects plasma levels of natriuretic peptides are impaired; furthermore peptide receptor polymorphisms have been shown to be significantly associated with hypertension and cardiac hypertrophy. Studying normotensive subjects at high genetic risk of developing hypertension on the basis of family history makes it possible to investigate the role of natriuretic peptide system in the genesis of hypertension. It has been shown that plasma atrial and ventricular natriuretic peptide levels are significantly reduced in normotensive subjects with a family history of hypertension. Our study is the first one showing association among positive family history of essential hypertension and natriuretic peptide receptor polymorphisms. We identified a novel insertion/deletion polymorphism at position 15,129 in the 3'-untranslated region (3'-UTR) of NPRA receptor mRNA. The NPRA gene deletion variant is associated with hypertensive family history and higher systolic blood pressure. The "deletion 15129" variant might participate in the functional impairment of natriuretic peptide system defining an increased genetic susceptibility to hypertension.
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PMID:[Natriuretic peptides and essential arterial hypertension]. 1250 9

We assessed whether large-scale expression profiling of leukocytes of patients with essential hypertension reflects characteristics of systemic disease and whether such changes are responsive to antihypertensive therapy. Total RNA from leukocytes were obtained from untreated (n=6) and treated (n=6) hypertensive patients without apparent end-organ damage and from normotensive controls (n=9). RNA was reverse-transcribed and labeled and gene expression analyzed using a 19-K oligonucleotide microarray using dye swaps. Samples of untreated and of treated patients were pooled for each sex and compared with age- and sex-matched controls. In untreated patients, 680 genes were differentially regulated (314 up and 366 down). In the treated patients, these changes were virtually absent (4 genes up, 3 genes down). A myriad of changes was observed in pathways involved in inflammation. Inflammation-dampening interleukin receptors were decreased in expression. Intriguingly, inhibitors of cytokine signaling (the PIAS family of proteins) were differentially expressed. The expression of several genes that are involved in regulation of blood pressure were also differentially expressed: angiotensin II type 1 receptor, ANP-A receptor, endothelin-2, and 3 of the serotonin receptors were increased, whereas endothelin-converting enzyme-1 was decreased. Strikingly, virtually no changes in gene expression could be detected in hypertensive patients who had become normotensive with treatment. This observation substantiates the long-standing idea that hypertension is associated with a complex systemic response involving inflammation-related genes. Furthermore, leukocytes display differential gene expression that is of importance in blood pressure control. Importantly, treatment of blood pressure to normal values can virtually correct such disturbances.
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PMID:Broadly altered gene expression in blood leukocytes in essential hypertension is absent during treatment. 1500 37

Guanylyl cyclase (GC)-A (natriuretic peptide receptor [NPR]-1), the receptor for atrial and brain natriuretic peptide, is important in the regulation of blood pressure in animal models and, possibly, in humans. In this study, we examined the association between dinucleotide repeat polymorphism within the 5'-flanking region of the GC-A gene and essential hypertension in a group of Japanese subjects. By genotyping 177 hypertensive and 170 normotensive subjects, we identified 5 allele types with 6, 9, 10, 11 and 12 CT dinucleotide repeats, respectively, around position -293, upstream of the ATG codon in the human GC-A gene. The frequency of the (CT)n=6 allele was significantly higher among hypertensive than normotensive subjects, while the frequencies of the other allele types did not differ between the two groups. We also examined the linkage between G/A polymorphism at position -77 (rs13306004), downstream of the (CT)n polymorphism, and found that the (CT)n=6 allele was tightly linked to an A at position -77, while all other (CT)n alleles were linked to G. Promoter-reporter analyses carried out in cultured human aortic smooth muscle cells using a luciferase gene fused to the 5'-flanking region of the GC-A gene revealed that the promoter containing (CT)n=6 drove less transcriptional activity than that containing (CT)n=10. Finally, site-directed mutation showed that the (CT)n and G/A polymorphisms act synergistically to affect GC-A promoter activity. Our results thus define the (CT)n polymorphism in the 5'-flanking region of the GC-A gene as a potent and novel susceptibility marker for hypertension.
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PMID:Association of CT dinucleotide repeat polymorphism in the 5'-flanking region of the guanylyl cyclase (GC)-A gene with essential hypertension in the Japanese. 1836 23

Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide receptor (NPR-B), and type C natriuretic peptide receptor (NPR-C). NPR-A and NPR-B are guanylyl cyclase receptors that increase intracellular cGMP concentration and activate cGMP-dependent protein kinases. NPR-C has been presented as a clearance receptor and its activation also results in inhibition of adenylyl cyclase activity. The wide range of effects of natriuretic peptides might be the base for the development of new therapeutic strategies of great benefit in patients with cardiovascular problems including coronary artery disease or heart failure. This review summarizes current literature concerning natriuretic peptides, their receptors and their effects on fluid/electrolyte balance, and vascular and cardiac physiology and pathology, including primary hypertension and myocardial infarction. In addition, we will attempt to provide an update on important issues regarding natriuretic peptides in congestive heart failure.
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PMID:Natriuretic peptides in vascular physiology and pathology. 1870 4

Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones, secretions of which are markedly upregulated during cardiac failure, making their plasma levels clinically useful diagnostic markers. ANP and BNP exert potent diuretic, natriuretic and vasorelaxant effects, which are mediated via their common receptor, guanylyl cyclase (GC)-A (also called natriuretic peptide receptor (NPR)-A). Mice deficient for GC-A are mildly hypertensive and show marked cardiac hypertrophy and fibrosis that is disproportionately severe, given their modestly higher blood pressure. Indeed, the cardiac hypertrophy seen in these mice is enhanced in a blood pressure-independent manner and is suppressed by cardiomyocyte-specific overexpression of GC-A. These results suggest that the actions of a local cardiac ANP/BNP-GC-A system are essential for maintenance of normal cardiac architecture. In addition, GC-A was shown to exert its cardioprotective effects by inhibiting angiotensin II-induced hypertrophic signaling, and recent evidence suggests that regulator of G protein signaling (RGS) subtype 4 is involved in the GC-A-mediated inhibition of Galphaq-coupled hypertrophic signal transduction. Furthermore, several different groups have reported that functional mutations in the promoter region of the human GC-A gene are associated with essential hypertension and ventricular hypertrophy. These findings suggest that endogenous GC-A protects the heart from pathological hypertrophic stimuli, and that humans who express only low levels of GC-A are genetically predisposed to cardiac remodeling and hypertension.
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PMID:Natriuretic Peptide Signaling via Guanylyl Cyclase (GC)-A: An Endogenous Protective Mechanism of the Heart. 2006 48

NPRA and NPRC are candidate susceptibility genes for essential hypertension (EH) and play a key role in the regulation of plasma levels and biological effects of natriuretic peptides. The aims of the present study were to find new genetic markers in the NPRA and NPRC genes and to assess relationships between variants and EH. A total of 797 unrelated Mongolian herdsmen were enrolled, including 389 EH patients and 408 normotensive controls. Genotyping was performed using the polymerase chain reaction/ligase detection reaction assay. The distribution of the T-allele frequency of rs1847018 in NPRC differed significantly between hypertensive subjects and controls. There was an association between rs1847018 and EH in the additive model in NPRC (P < 0.05). There were no significant differences in the genotype and allele frequency distributions for any of the 3 single nucleotide polymorphisms in NPRA between EH and normotensive individuals. In NPRA, the frequency of haplotype TCA in the EH group was significantly lower than in controls, while the frequency of haplotype TCG was significantly higher in the EH group than in controls; Individuals who possessed the TCA haplotype had a significantly lower risk of EH, whereas the presence of haplotype TCG was significantly associated with a higher risk of EH. However, there was no significant difference between the EH group and controls in any of the 8 haplotypes in NPRC. Rs1847018 is a genetic marker of EH in NPRC, and the frequency of haplotype TCA and TCG in NPRA is associated with EH in the Mongolian population.
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PMID:Association of NPRA and NPRC gene variants and hypertension in Mongolian population. 2678 97