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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Ageing and hypertension are associated with changes in the way in which the body handles sodium. This may involve changes in plasma atrial natriuretic peptide concentration, since atrial natriuretic peptide is a regulator of sodium handling by the kidney and the plasma atrial natriuretic peptide concentration is increased in both ageing and hypertension. An increase in the plasma atrial natriuretic peptide concentration could also be associated with a change in atrial natriuretic peptide receptor density, possibly involving down-regulation. 2. To investigate these possibilities plasma atrial natriuretic peptide concentration and platelet atrial natriuretic peptide binding site density were measured in 18 young, 11 middle-aged and 12 elderly healthy subjects and in 23 patients with mild to moderate essential hypertension. 3. In normotensive subjects, the plasma atrial natriuretic peptide concentration increased with age (r = 0.49, P less than 0.01) and was significantly higher in elderly than young subjects (mean +/- SEM, 31.9 +/- 4.5 versus 18.3 +/- 2.0 pmol/l, P less than 0.05). The plasma atrial natriuretic peptide concentration increased with the mean arterial pressure in normotensive subjects (r = 0.47, P less than 0.01). Multiple regression analysis did not show independent relationships between the plasma atrial natriuretic peptide concentration and either age or mean arterial pressure in normotensive subjects alone. However, when normotensive subjects and hypertensive patients were considered together, multiple regression revealed both age and mean arterial pressure as independent predictors of the plasma atrial natriuretic peptide concentration (P less than 0.05, P less than 0.01, respectively). In normotensive subjects, the platelet atrial natriuretic peptide binding site density did not change with age (r = 0.19, P = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma atrial natriuretic peptide concentration and platelet atrial natriuretic peptide binding site density in ageing and hypertension. 165 97

Recent progress has been remarkable in identifying mutations which cause diseases (mostly uncommon) that are inherited simply. Unfortunately, the common diseases of humankind with a strong genetic component, such as those affecting cardiovascular function, have proved less tractable. Their etiology is complex with substantial environmental components and strong indications that multiple genes are implicated. In this article, we consider the genetic etiology of essential hypertension. After presenting the distribution of blood pressures in the population, we propose the hypothesis that essential hypertension is the consequence of different combinations of genetic variations that are individually of little consequence. The candidate gene approach to finding relevant genes is exemplified by studies that identified potentially causative variations associated with quantitative differences in the expression of the angiotensinogen gene (AGT). Experiments to test causation directly are possible in mice, and we describe their use to establish that blood pressures are indeed altered by genetic changes in AGT expression. Tests of differences in expression of the genes coding for the angiotensin-converting enzyme (ACE) and for the natriuretic peptide receptor A are also considered, and we provide a tabulation of all comparable experiments in mice. Computer simulations are presented that resolve the paradoxical finding that while ACE inhibitors are effective, genetic variations in the expression of the ACE gene do not affect blood pressure. We emphasize the usefulness of studying animals heterozygous for an inactivating mutation and a wild-type allele, and briefly discuss a way of establishing causative links between complex phenotypes and single nucleotide polymorphisms.
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PMID:Importance of quantitative genetic variations in the etiology of hypertension. 1111 61

Genetic susceptibility to common conditions, such as essential hypertension and cardiac hypertrophy, is probably determined by various combinations of small quantitative changes in the expression of many genes. NPR1, coding for natriuretic peptide receptor A (NPRA), is a potential candidate, because NPRA mediates natriuretic, diuretic, and vasorelaxing actions of the nariuretic peptides, and because genetically determined quantitative changes in the expression of this gene affect blood pressure and heart weight in a dose-dependent manner in mice. To determine whether there are common quantitative variants in human NPR1, we have sequenced the entire human NPR1 gene and identified 10 polymorphic sites in its non-coding sequence by using DNA from 34 unrelated human individuals. Five of the sites are single nucleotide polymorphisms; the remaining five are length polymorphisms, including a highly variable complex dinucleotide repeat in intron 19. There are three common haplotypes 5' to this dinucleotide repeat and three 3' to it, but the 5' haplotypes and 3' haplotypes appear to be randomly associated. Transient expression analysis in cultured cells of reporter plasmids with the proximal promoter sequences of NPR1 and its 3' untranslated regions showed that these polymorphisms have functional effects. We conclude that common NPR1 alleles can alter expression of the gene as much as two-fold and could therefore significantly affect genetic risks for essential hypertension and cardiac hypertrophy in humans.
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PMID:Common variations in noncoding regions of the human natriuretic peptide receptor A gene have quantitative effects. 1248 1