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 collagen-provocated platelet nitric oxide synthase (NOS) activity by the method of 3H-labelled L-arginine was compared between 19 essential hypertensives (EH) and 21 controls, and between 13 adolescents with their both parent hypertensives (FH+) and 12 adolescents without genetic hypertensive predisposition (FH-) as well. Results showed that the platelet NOS activity was lower significantly in EH group (4.76 +/- 2.01 vs 8.09 +/- 2.36 pmol.g-1.min-1, P < 0.001) and in FH+ group (3.64 +/- 2.07 vs 5.51 +/- 2.13 pmol.g-1.min-1, P < 0.05) comparing with their control groups respectively. It suggests that the inherited defect of some anti-hypertensive mechanisms like NO/NOS system may be implicated in the development of EH, which can be taken as a new "genetic marker" for detecting of specific clinic subtype. An useful data was thus presented of value in screening referred genes, for early prevention and rational remedy in essential hypertension.
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PMID:[Inherited defect of platelet nitric oxide synthase activity in essential hypertension]. 1043 65

We examined some immunological parameters, particularly cytokines and soluble factors in collagen diseases complicated with essential hypertension. We also investigated the effects of Nilvadipine on immunological parameters after treatment with this drug for six months. The frequency of helper/inducer T cells (CD4+ CD8- cells, CD4+ CD45RA- cells) decreased in the peripheral blood on a 6 month treatment with nilvadipine. There was a significant decrease of suppressor/inducer T cells (CD4+ 45RA+ cells), and an insignificant decrease of activated T cells (CD3+ HLA-DR+ cells) and memory T cells (CD45RA- CD45RO+ cells) after treatment. Before treatment with Nilvadipine, interleukin-1beta, tumor necrosis factor-a, and interleukin-6 levels increased higher in the patients than in healthy volunteers. However, interleukin-1beta and interleukin-6 concentrations tended to decrease after treatment with Nilvadipine. Besides, tumor necrosis factor-alpha decreased significantly after treatment. The soluble interleukin-2 receptor concentrations also showed a decreased tendency after treatment, although high concentrations were found in the patients before treatment. In contrast, soluble human leukocyte antigen-1 and soluble thrombomodulin levels showed no significant change after treatment. These results suggest that Nilvadipine inhibits the generation of cytokines derived from activated T lymphocytes. Nilvadipine, calcium antagonist, may be useful for inhibition of vascular complication in collagen diseases.
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PMID:Effects of nilvadipine on cytokine-levels and soluble factors in collagen disease complicated with essential hypertension. 1051 35

Left ventricular (LV) hypertrophy is an independent risk factor for cardiovascular morbidity and mortality. Experimental data revealed that elevated circulating aldosterone is associated with increased collagen accumulation resulting in myocardial fibrosis. To analyze whether aldosterone is also associated with cardiac structural and functional changes in humans, we examined the effects of aldosterone on LV structure and function before and after suppression of aldosterone by increasing oral salt intake. The study group comprised 26 normotensive male white healthy control subjects (age 26 +/- 3 years) and 31 male white subjects (age 25 +/- 3 years) with mild essential hypertension (World Health Organization stages I to II). Two-dimensional-guided M-mode echocardiography and 24-hour ambulatory blood pressure (BP) monitoring was performed in each subject. Simultaneously, we measured 24-hour urinary sodium excretion, 24-hour urinary aldosterone, and serum aldosterone concentration at baseline and after increasing oral salt intake to suppress aldosterone secretion. In all subjects LV mass correlated with body mass index (r = 0.42, p <0.001) and both 24-hour ambulatory systolic (r = 0.28, p <0.05) and diastolic (r = 0.25, p <0.05) BP. Changes in urinary sodium excretion correlated inversely with changes in serum aldosterone concentration (r = -0.28; p <0.05). Urinary aldosterone concentration after salt loading decreased in normotensive (10.98 vs 7.44 microg/24 hours; p <0.02) but not in hypertensive (9.34 vs 10.51 microg/24 hours; p = NS) subjects. Serum and urinary aldosterone levels at baseline were not related to LV structure or function. In contrast, after increasing oral salt intake, urinary aldosterone concentration was related to LV mass (r = 0.43; p <0.01) and impaired midwall fractional fiber shortening (r = -0.33; p <0.02) in all subjects, independent of 24-hour ambulatory BP. Subgroup analysis revealed that this was significant only in hypertensive (r = 0.46; p <0.01 and r = -0.44; p <0.02, respectively) but not in normotensive (r = 0.28 and -0.16; p = NS for both, respectively) subjects. Consistently, the greater serum aldosterone remained after increasing oral salt intake, the greater was LV mass (r = 0.35; p <0.01). The latter was found in hypertensive subjects (r = 0.44; p <0.02), independent of 24-hour ambulatory BP, but not in normotensive subjects (r = 0.025; p = NS). Inadequate suppression of aldosterone in response to an increase in oral salt intake is related to LV structural and functional changes in hypertensive subjects. Thus, our results support experimental data indicating that aldosterone affects LV structure and function in humans and that this effect is BP independent.
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PMID:Impact of aldosterone on left ventricular structure and function in young normotensive and mildly hypertensive subjects. 1080 1

In hypertensive heart disease, no data are available on the repair of coronary resistance vessels in patients after long-term ACE inhibitor treatment. Fourteen patients with essential hypertension were studied with coronary flow reserve and with transvenous endomyocardial biopsy before and after 12 months of antihypertensive treatment with perindopril (4 to 8 mg/d, mean 5.9+/-2.3 mg/d). Left ventricular muscle mass index decreased by 11% (from 145+/-41 to 128+/-36 g/m(2), P=0.04). Maximal coronary blood flow was increased by 54% (from 170+/-46 to 263+/-142 mL. min(-1). 100 g(-1), P=0.001), and minimal coronary vascular resistance was diminished by 33% (from 0.67+/-0.21 to 0.45+/-0.19 mm Hg. min. 100 g. mL(-1), P=0.001); consequently, coronary reserve increased by 67% from 2.1+/-0.6 to 3. 5+/-1.9 (P=0.001). Structural analysis revealed regression of periarteriolar collagen area by 54% (from 558+/-270 to 260+/-173 microm(2), P=0.04) and of total interstitial collagen volume density by 22% (from 5.5+/-3.8 Vv% to 4.3+/-3.2 Vv%, P=0.04), whereas arteriolar wall area was slightly but not significantly reduced. Long-term therapy with the ACE inhibitor perindopril induces structural repair of coronary arterioles that is mainly characterized by the regression of periarteriolar fibrosis and associated with a marked improvement in coronary reserve. These findings indicate the beneficial reparative effects of ACE inhibition on coronary microcirculation in hypertensive heart disease.
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PMID:Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease. 1094 81

A substantial increase in fibrillar collagen has been observed in the left cardiac ventricle of animals and humans with arterial hypertension. Hypertensive myocardial fibrosis is the result of both increased collagen types I and III due to the fact that its synthesis by fibroblasts and myofibroblasts is stimulated and its extracellular collagen degradation unchanged or decreased extracellular collagen degradation. Hemodynamic and non-hemodynamic factors may be involved in the disequilibrium between collagen synthesis and degradation that occurs in hypertension. As shown experimentally and clinically, an exaggerated rise in fibrillar collagen content promotes abnormalities of cardiac function, contributes to the decrease in coronary reserve and facilitates alterations in the electrical activity of the left ventricle. Although microscopic examination of cardiac biopsies is the most reliable method for documenting and measuring myocardial fibrosis, the development of non-invasive methods to indicate the presence of myocardial fibrosis in hypertensive patients would be useful. We have therefore applied a biochemical method based on the measurement of serum peptides derived from the tissue formation when synthesized and degradation of fibrillar collagens to monitor the turnover of these molecules in rats with spontaneous hypertension and patients with essential hypertension.
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PMID:[Biochemical diagnosis of hypertensive myocardial fibrosis]. 1100 63

We investigated whether a relationship exists between circulating transforming growth factor beta -1 (TGF-beta(1)), collagen type I metabolism, microalbuminuria, and left ventricular hypertrophy in essential hypertension and whether the ability of the angiotensin II type 1 receptor antagonist losartan to correct microalbuminuria and regress left ventricular hypertrophy in hypertensives is related to changes in TGF-beta(1) and collagen type I metabolism. The study was performed in 30 normotensive healthy controls and 30 patients with never-treated essential hypertension classified into 2 groups: those with microalbuminuria (urinary albumin excretion >30 and <300 mg/24 h) associated with left ventricular hypertrophy (left ventricular mass index >116 g/m(2) for men and >104 g/m(2) for women) (group B; n=17) and those without microalbuminuria or left ventricular hypertrophy (group A; n=13). The measurements were repeated in all patients after 6 months of treatment with losartan (50 mg once daily). The serum concentration of TGF-beta(1) was measured by a 2-site ELISA method, and the serum concentrations of carboxy-terminal propeptide of procollagen type I (a marker of collagen type I synthesis) and carboxy-terminal telopeptide of collagen type I (a marker of collagen type I degradation) were measured by specific radioimmunoassays. The duration of hypertension and baseline values of blood pressure were similar in the 2 groups of patients. No differences in serum TGF-beta(1), carboxy-terminal propeptide of procollagen type I, and carboxy-terminal telopeptide of collagen type I were found between normotensives and group A of hypertensives. Serum TGF-beta(1), carboxy-terminal propeptide of procollagen type I, and the ratio of carboxy-terminal propeptide of procollagen type I to carboxy-terminal telopeptide of collagen type I were increased (P<0.05) in group B of hypertensives compared with group A of hypertensives and normotensives. No differences in carboxy-terminal telopeptide of collagen type I were found among the 3 groups of subjects. After treatment with losartan, microalbuminuria and left ventricular hypertrophy persisted in 6 patients (then considered nonresponders) and disappeared in 11 patients (then considered responders) from group B. Compared with nonresponders, responders exhibited similar control of blood pressure and higher (P<0.05) blockade of angiotensin II type 1 receptors (as assessed by a higher increase in plasma levels of angiotensin II). Whereas TGF-beta(1), carboxy-terminal propeptide of procollagen type I, and the ratio of carboxy-terminal propeptide of procollagen type I to carboxy-terminal telopeptide of collagen type I decreased (P<0.05) in responders, no changes in these parameters were observed in nonresponders. These findings show that an association exists between an excess of TGF-beta(1), stimulation of collagen type I synthesis, inhibition of collagen type I degradation, and cardiorenal damage in a group of patients with essential hypertension. In addition, our results suggest that the ability of losartan to blunt the synthesis of TGF-beta(1) and normalize collagen type I metabolism may contribute to protect the heart and the kidney in a fraction of patients with essential hypertension.
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PMID:Transforming growth factor beta in hypertensives with cardiorenal damage. 1104 Feb 29

We recently demonstrated that spironolactone may have beneficial effects on left ventricular hypertrophy in selected patients with essential hypertension undergoing treatment with an angiotensin-converting enzyme (ACE) inhibitor. To clarify the possible mechanisms by which spironolactone improves cardiac hypertrophy, we investigated the change in serum procollagen type III amino-terminal peptide (PIIINP) in 11 patients with essential hypertension treated with spironolactone and an ACE inhibitor for 24 weeks. Both blood pressure and serum PIIINP levels were significantly decreased by treatment. There was a statistical significant correlation between the changes in LVMI and those in PIIINP. The reduction in PIIINP was significant in patients whose initial serum PIIINP levels were above the normal range. Before treatment, there were no statistically significant correlations between serum PIIINP levels and either LVMI, blood pressure, or plasma aldosterone concentration. Essential hypertensive patients matched in terms of duration of therapy, blood pressure and LVMI and treated with an ACE inhibitor alone showed no change in serum PIIINP levels. In conclusion, the results of the present study demonstrate that patients with essential hypertension and high serum levels of PIIINP are particularly responsive to MR blockade in terms of left ventricular hypertrophy. Moreover, these results suggest that spironolactone limits cardiac collagen turnover in such patients. Larger studies may provide definitive evidence for the involvement of aldosterone in left ventricular hypertrophy in patients with abnormally high PIIINP levels.
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PMID:High serum level of procollagen type III amino-terminal peptide contributes to the efficacy of spironolactone and angiotensin-converting enzyme inhibitor therapy on left ventricular hypertrophy in essential hypertensive patients. 1132 81

A disproportionate accumulation of fibrillar collagen is a characteristic feature of hypertensive heart disease, but the extent of myocardial fibrosis may differ in different models of hypertension. In experimental studies, aldosterone and endothelins emerge as important determinants of myocardial fibrosis. Changes in myocardial extracellular matrix and collagen deposition can be estimated noninvasively by analysis of the ultrasonic backscatter signal, which arises from tissue heterogeneity within the myocardium and describes myocardial texture. This study was designed to investigate the relations between myocardial integrated backscatter and circulating aldosterone and immunoreactive endothelin in human hypertension. The study population consisted of 56 subjects: 14 healthy normotensive volunteers and 42 hypertensive patients (14 with primary aldosteronism, 7 with renovascular hypertension, and 21 with essential hypertension). The patients with essential and secondary hypertension were matched for age, gender, body mass index, and blood pressure. Myocardial integrated backscatter at diastole was 19.8+/-2.0 and 20.8+/-2.9 decibels in normotensive control subjects and patients with essential hypertension and significantly higher in patients with primary aldosteronism (27.4+/-3.8 decibels, P<0.01) and renovascular hypertension (26.8+/-4.8 decibels, P<0.01). In the population as a whole, as well as in the hypertensive subpopulation, myocardial integrated backscatter was directly related to plasma aldosterone (r=0.73 and 0.71, P<0.01 for both) and immunoreactive endothelin (r=0.60 and 0.56, P<0.01 for both). The data of this study suggest that in human hypertension, circulating aldosterone and immunoreactive endothelin may induce alterations in left ventricular myocardial texture, possibly related to increased myocardial collagen content.
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PMID:Myocardial ultrasonic backscatter in hypertension: relation to aldosterone and endothelin. 1257 87

This study was designed to test the hypothesis that plasma concentrations of matrix metallo-proteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two enzymes that share similar substrate specificity (collagen type IV and V), possibly related to vascular remodelling, are altered in essential hypertension. The second aim of the study was to assess whether chronic antihypertensive treatment with the calcium channel blocker amlodipine would normalize these alterations. To test this hypothesis, we measured plasma concentrations of active MMP-2 and MMP-9 in 42 patients with never-treated essential hypertension and in 25 normotensive control subjects. Measurements were repeated after 6 months of treatment with the calcium channel blocker amlodipine. Baseline values of MMP-2 and MMP-9 were decreased (P=0.01 and 0.002, respectively) in hypertensive patients compared with normotensives. Hypertensive patients with systemic vascular resistances <1440 dyn s/cm(5) exhibited higher values of MMP-2 (P=0.005) and MMP-9 (P=0.001) than hypertensive patients with systemic vascular resistances >1440 dyn s/cm(5). Treated patients attained a nonsignificant increase in MMP-2 plasma concentrations, but a significant increase in MMP-9 plasma concentrations (P=0.01) compared to respective values before treatment. In conclusion, these findings suggest that plasma concentrations of active MMP-2 and MMP-9, mainly related to vascular extracellular matrix metabolism, are depressed in patients with essential hypertension. A 6 month treatment with amlodipine can normalize MMP-9 but not MMP-2 plasma concentrations. The hypothesis that antihypertensive treatment may modulate collagen metabolism remains to be determined by further studies.
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PMID:Plasma levels of active extracellular matrix metalloproteinases 2 and 9 in patients with essential hypertension before and after antihypertensive treatment. 1257 90

Epidemiological studies have demonstrated that pulse pressure and arterial stiffness are strong independent risk factors for all-cause and cardiovascular mortality, primary coronary heart disease (CHD) and stroke. Thus, treatment of hypertension and congestive heart failure (CHF) should aim to reduce arterial stiffness in order to lower afterload and pulse pressure, promote regression of left ventricular and arterial wall hypertrophy and, in CHF, increase cardiac output. Elevation of diastolic blood pressure appears to be beneficial to coronary perfusion and this may be particularly relevant in the setting of CHD. In patients with essential hypertension, numerous studies have shown a decrease in arterial stiffness with various pharmacological classes of antihypertensive agents (including beta-blockers, diuretics, ACE inhibitors, angiotensin II receptor antagonists and calcium antagonists), either acutely or during long-term studies. Their efficacy is not surprising, since blood pressure reduction unloads the stiff components of the arterial wall, such as collagen. However, it seems likely that pharmacological treatment has the capacity to decrease arterial stiffness beyond blood pressure reduction, because long-term drug administration can modify the wall components, including a reduction in collagen density or changes in the spatial arrangement of the wall materials. Whether classes of antihypertensive agents vary in their efficacy to affect arterial structure and thus influence arterial stiffness via a pressure-independent mechanism is more controversial and has yet to be evaluated in large-scale trials. A Consensus Conference on the 'Clinical Applications of Arterial Stiffness', held in Paris, June 17, 2000, recommended guidelines for further pharmacological and therapeutic studies on arterial stiffness. Among them were the following: 'To reach full normalisation of arterial stiffness, pharmacological and therapeutic trials should aim at lowering systolic and diastolic blood pressure to a larger extent than in previous studies and giving treatments for a longer duration than in most previous studies;Mainly, studies designed to demonstrate the prognostic value of the reduction of arterial stiffness are urgently needed. They should be performed in patients at high cardiovascular risk, on a large scale and a long-term basis, and include all-cause and cardiovascular mortality and cardiovascular morbidity'.
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PMID:[Drugs and arterial stiffness in hypertensive patients]. 1270 78


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