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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. There is evidence to suggest that essential hypertension is a polygenic disorder and that it arises from yet-to-be-identified predisposing variants of certain genes that influence blood pressure. The cloning of various hormone, enzyme, adrenoceptor and hormone receptor genes whose products are involved in blood pressure control and the identification of polymorphisms of these has permitted us to test their genetic association with hypertension. 2. Cross-sectional analyses of a number of candidate gene markers were performed in hypertensive and normotensive subjects who were selected on the basis of both parents being either hypertensive or normotensive, respectively, and the difference in total alleles on all chromosomes for each polymorphism between the hypertensive and normotensive groups was tested by chi 2 analysis with one degree of freedom. 3. A marked association was observed between hypertension and insertion alleles of polymorphisms of the insulin receptor gene (INSR) (P < 0.0040) and the dipeptidyl carboxypeptidase-1 (angiotensin I-converting enzyme; kininase II) gene (DCP1) (P < 0.0018). No association with hypertension was evident, however, for polymorphisms of the growth hormone, low-density lipoprotein receptor, renal kallikrein, alpha 2- and beta 1-adrenoreceptor, atrial natriuretic factor and insulin genes. 4. All but one of the hypertensive subjects had at least one of the hypertension-associated alleles, and although subjects homozygous for both were three times more frequent in the hypertensive group, examination of the nine possible genotypes suggested that the INSR and DCP1 alleles are independent markers for hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Independent, marked associations of alleles of the insulin receptor and dipeptidyl carboxypeptidase-I genes with essential hypertension. 810 54

Angiotensin I and II are generated by the vascular wall. Whether this generation depends on renin or on other enzymes is debated. We tested the hypothesis that remikiren, a highly specific inhibitor of human and guinea pig renin, may inhibit the vascular renin-angiotensin system. Isolated hindquarters from guinea pigs were perfused with an artificial medium, and angiotensin I and II release was measured by high-performance liquid chromatography and radioimmunoassay. Guinea pig hindquarters released angiotensin I (23.8 +/- 5.6 fmol/30 min; n = 13) and angiotensin II (95.2 +/- 19 fmol/30 min; n = 13) spontaneously. Inhibition of the angiotensin I-converting enzyme by captopril (10 nmol/mL) suppressed angiotensin II by 85% and increased angiotensin I by 352% (n = 5, P < .05). Infusion of remikiren (1.6 nmol/mL) in addition to captopril decreased angiotensin I release by 68% (P < .05 versus captopril alone, n = 5 each). We conclude that renin generates angiotensin I in an isolated guinea pig resistance vessel bed. Our study demonstrates that renin rather than nonrenin enzymes is responsible for the major part of vascular angiotensin formation.
Hypertension 1994 Jun
PMID:Vascular renin in the guinea pig. Suppression by the renin inhibitor remikiren. 820 19

The authors review recent therapeutic procedures in arterial hypertension associated with renal disease. Treatment of hypertension is comprehensive, it comprises non-medicamentous procedures, pharmacotherapy and in some affections also interventional and surgical therapy. Effective reduction of the blood pressure to values < or = 140/90 mmHg unequivocally retards progression of renal disease, the development of nephrosclerosis and delays the development of renal insufficiency. In medicamentous treatment of nephrogenic hypertension a wide range of conventional antihypertensive drugs is used. Their selection and dosage must be adapted to the type of the basic renal disease and the reduction of renal functions. Recently the demand has been raised that the antihypertensive drugs used should possess in addition to the blood pressure lowering effect also an additive renoprotective effect ensuing above all from diminished intraglomerular hypertension and undesirable hyperfiltration, a changed permeability of capillary membranes due to reduction of microalbuminuria and proteinuria or restriction of proliferation procedures. These demands are met by the angiotensin I-converting enzyme (ACEI) inhibitor. If the correct dosage is used, ACEI are, due to their excellent antihypertensive action, absence of undesirable metabolic sequelae and significant renoprotective effect, drugs of the first line in nephrogenic hypertension. The authors use above all ACEI with a long-term effect, i.e. those without a SH group in the molecule. Very small doses (e.g. 2.5 mg Enalapril per day) reduce microalbuminuria and proteinuria and retard progression of nephrosclerosis also in nephropathies without systemic hypertension, e.g. in diabetic glomerulosclerosis. The renoprotective effect is manifested more markedly in initial stages of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of hypertension in kidney diseases]. 821 33

1. The gene for dipeptidyl carboxypeptidase 1 (angiotensin I-converting enzyme, kininase II; DCP1), located on chromosome 17q23, has been implicated in hypertension in rats. In humans associations have been found for the insertion allele of a bi-allelic insertion/deletion polymorphism of DCP1 with hypertension and the deletion allele with myocardial infarction. Other hypertension studies have, however, failed to find a relationship. 2. Mathematical predictions based on DCP1 association data suggest that high sib-pair numbers may be needed to achieve statistical significance by this approach, although differences in the severity of hypertension in different study groups could account for the disparate findings. 3. No association was found between DCP1 allele or genotype frequencies and obesity in essential hypertensives.
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PMID:Chromosome 17q23: a locus for cardiovascular disease. 839 42

An insertion (I)/deletion (D) polymorphism of the angiotensin I-converting enzyme (ACE) gene that has been associated with certain cardiovascular disorders accounts for nearly half the variation in serum ACE level in white subjects. Whether a similar association of serum ACE with the I/D polymorphism occurs in other racial groups is not known. We studied the I/D polymorphism of ACE in relation to serum ACE activity in 141 white and 62 black healthy, unrelated children and adolescents (mean age, 14.7 years). The mean level of ACE activity in whites homozygous for the D allele was higher than in heterozygotes (P = .002) and in homozygotes for the I allele (P = .0001), consistent with an earlier study. In blacks, on the other hand, no significant difference in serum ACE activity between genotypes was observed. An additional finding was a significantly positive relationship between serum ACE activity and diastolic pressure (P = .009). In children and adolescents, serum ACE activity is related to the ACE gene I/D polymorphism in whites but not in blacks. The results indicate a potentially important ethnic variation in genetic regulation of serum ACE activity and the relationship of the I/D polymorphism to cardiovascular disease.
Hypertension 1996 Jan
PMID:Racial difference in the relationship of an angiotensin I-converting enzyme gene polymorphism to serum angiotensin I-converting enzyme activity. 859 89

We undertook the present study in 66 Japanese patients with essential hypertension to identify genetic factors associated with salt sensitivity. Patients were classified into salt-sensitive or salt-resistant groups on the basis of changes in their mean blood pressures from a week of a low salt diet (50 mmol/d) to a week of a high salt diet (340 mmol/d). Salt sensitivity and resistance were studied in relation to a 287-bp insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme gene detected by a polymerase chain reaction method and the haptoglobin phenotype determined by polyacrylamide gel electrophoresis. Patients with the angiotensin I-converting enzyme gene genotype II were more apt to be salt sensitive than patients with the ID and DD genotypes, although plasma renin activity was similar in each group. The frequency of the I allele in the salt-sensitive group was significantly higher than that in the salt-resistant group (chi2 = 7.4, odds ratio = 2.78). However, there was no significant relationship between haptoglobin phenotype and salt sensitivity. These data suggest that an I/D polymorphism of the angiotensin I-converting enzyme gene is a genetic factor associated with salt sensitivity of blood pressure independently of plasma renin activity in Japanese patients with essential hypertension.
Hypertension 1996 Mar
PMID:Angiotensin I-converting enzyme gene polymorphism and salt sensitivity in essential hypertension. 861 5

In the present study, we studied angiotensin II type 1 (AT1) and type 2 (AT2) receptor messengers by quantitative reverse transcriptase-polymerase chain reaction. We examined peripheral blood mononuclear cells from 30 healthy subjects and 50 subjects with primary hypertension, in whom angiotensin I-converting enzyme genotype was determined, before and after 15 days of treatment with different antihypertensive drugs. The medication included a calcium channel antagonist, an angiotensin I-converting enzyme inhibitor, and a beta 1-blocker. We also studied the relationship between AT1 receptor gene expression and biochemical parameters of the renin-angiotensin system. AT1 receptor messenger levels were positively correlated with plasma renin activity in both normotensive and untreated hypertensive subjects. Increases of this messenger and plasma angiotensin II levels were correlated with the D allele in the same individuals. AT1 receptor messenger levels decreased significantly with angiotensin I-converting enzyme inhibitor treatment in subjects with the DD genotype, and a significant decrease was observed in subjects with the II and ID genotypes treated with a calcium antagonist. No changes were observed in mRNA with the beta 1-blocker. We conclude that the AT2 receptor is not expressed in peripheral leukocytes and that AT1 receptor messenger levels vary in relation to angiotensin I-converting enzyme genotype and pharmacological treatment. These results suggest that angiotensin I-converting enzyme genotype may be an important factor when deciding on antihypertensive therapy in individuals with primary hypertension.
Hypertension 1996 Jul
PMID:Angiotensin I-converting enzyme genotypes and angiotensin II receptors. Response to therapy. 867 71

Inhibition of nitric oxide synthase by L-arginine analogues such as N omega-nitro-L-arginine methyl ester (L-NAME) in spontaneously hypertensive rats (SHR) is associated with malignant hypertension and enhanced expression of the endothelin-1 gene in some blood vessels. In this study, SHR treated chronically with L-NAME (SHR-L-NAME) were given the angiotensin I-converting enzyme inhibitor cilazapril or the endothelin-A/endothelin-B receptor antagonist bosentan for 3 weeks. Systolic pressure was lowered slightly by cilazapril (213 +/- 2 versus 229 +/- 2 mm Hg in untreated SHR-L-NAME, P < .01) but was not significantly lowered by bosentan (223 +/- 2 mm Hg). Hypertrophy of aorta and small arteries (coronary, renal, mesenteric, and femoral) was decreased by cilazapril treatment and unaffected by bosentan. Expression of the endothelin-1 gene was evaluated in SHR-L-NAME by in situ hybridization histochemistry, which showed that endothelin-1 expression was enhanced in the endothelium of aorta but not in small mesenteric arteries in these rats. The absence of enhancement of endothelin-1 gene expression in small arteries may account for the absence of increased severity of hypertrophy of small vessels in SHR-L-NAME and may be a mechanism whereby L-NAME inhibits cardiovascular growth. These results suggest that in the absence of enhanced small-artery endothelin-1 expression, endothelin antagonism does not lower blood pressure. The blood pressure-lowering effect of angiotensin I-converting enzyme inhibition suggests a role for the renin-angiotensin system in the malignant form of hypertension that develops in SHR treated with L-NAME.
Hypertension 1996 Aug
PMID:Comparison of effect of endothelin antagonism and angiotensin-converting enzyme inhibition on blood pressure and vascular structure in spontaneously hypertensive rats treated with N omega-nitro-L-arginine methyl ester. Correlation with topography of vascular endothelin-1 gene expression. 870 80

1. This review argues that the deletion (D) allele of an insertion (I)/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene is a marker for a variant associated with increased ACE expression, as well as myocardial infarction (MI) and other life-threatening conditions. 2. By examination of I/D frequency in different age groups of individuals having well-known risk factors, it appears that homozygosity for the D allele may be associated with an increased risk of premature death in subjects at high-risk of cardiovascular events. For the risk factor hypertension, the odds ratio for DD vs II in patients aged > or = 60 years was 6.6. 3. Besides in MI itself, the DD genotype appears to be also more prevalent in MI patients who develop restenosis several months after balloon angioplasty, patients with various forms of heart failure, those with ventricular hypertrophy and diabetic patients who develop nephropathy. 4. Particular genotypes of other components of the renin-angiotensin system may add to the risk conferred by the ACE DD genotype. 5. Emerging evidence therefore suggests that the ACE genotype may eventually be placed on the list of common, well-known risk factors for fatal cardiovascular events.
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PMID:Hypothesis: an angiotensin converting enzyme genotype, present in one in three caucasians, is associated with increased mortality rate. 871 89

Angiotensin II may contribute to the altered structure and function of small arteries. We proposed that angiotensin I-converting enzyme (ACE) inhibitor treatment could induce a regression of vascular remodeling. A double-blind trial was performed comparing effects of the ACE inhibitor cilazapril with the beta-blocker atenolol on small arteries obtained from biopsy specimens of subcutaneous gluteal fat. Nine patients with essential hypertension were randomized to cilazapril and eight to atenolol. Blood pressure was below 140/95 mm Hg under treatment for the duration of the study in all patients. Media-to-lumen ratio of small arteries of the patients, which before treatment was significantly higher than in normotensive subjects, was corrected after 1 year of treatment in the cilazapril group. There was no change in the increased media-to-lumen ratio of small arteries in the atenolol group, even after 2 years of treatment. Attenuated constrictor responses to endothelin-1 returned to normal only in the patients treated with cilazapril. Endothelium-dependent relaxation responses to acetylcholine were slightly depressed in hypertensive patients and improved in the cilazapril-treated group, but remained blunted in the arteries of the atenolol-treated patients. Treatment with cilazapril corrects small artery remodeling and endothelium-related functional abnormalities of gluteal subcutaneous small arteries in hypertensive patients. It remains to be demonstrated whether these apparently beneficial effects translate into reduced morbidity and mortality in hypertension.
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PMID:Correction of remodeling and function of small arteries in human hypertension by cilazapril, an angiotensin I-converting enzyme inhibitor. 872 94


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