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)

Blood pressure (BP) oscillations contain rhythmic components of low-, mid-, and high-frequency bands (0.02-0.06, 0.07-0.14, 0.15-0.40 Hz, respectively). Baroreceptors may sense each BP oscillation and induce a buffer reaction. To clarify the frequency-dependent baroreflex response and its possible alteration in patients with high BP, both BP (Finapres) and the RR interval (electrocardiogram) were continuously monitored in untreated patients with essential hypertension (EH) (n = 52) and normotensive subjects (NT) (n = 43). The magnitude and phase response of cardiac beats to BP oscillations were examined by transfer function analysis. Spontaneous baroreflex sensitivity was assessed by linear regression analysis of the BP and RR oscillations. The heart rate responded linearly to BP oscillations in more subjects at mid- and high-frequency bands (83% or more) than at the low-frequency band (60% or less). The phase was approximately zero at the high-frequency band and was consistently negative at the mid- and low-frequency bands. In general, all frequency gains were significantly and positively correlated with spontaneous baroreflex sensitivity. Each frequency gain was smaller in EH patients than in NT subjects, the high-frequency gain more so than the gains at the lower frequencies. In seven young EH patients, treatment with a beta 1-adrenoceptor selective blocker normalized the high-frequency gain and tended to increase the gains at the lower frequencies. These results suggest that the spontaneous baroreflex modulates RR oscillations over a broad frequency range from 0.02 to 0.40 Hz; the effect was most marked at frequencies higher than 0.07 Hz. Furthermore the frequency-dependent characteristics of the cardiac baroreflex were altered in essential hypertension partly because of an increased beta-adrenergic activity.
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PMID:Altered frequency-dependent characteristics of the cardiac baroreflex in essential hypertension. 796 64

It was previously shown that the second extracellular loop of cardiovascular G-protein-coupled receptors is an antigenic target for pharmacologically active autoantibodies in patients with idiopathic dilated cardiomyopathy. To extend these observations to cover patients with the same disease from different geographical origins or to patients with other cardiac diseases, peptides corresponding to the sequences of the second extracellular loops of the human M2 muscarinic receptors and beta adrenoceptors were used as antigens in an enzyme immunoassay. Sera from patients from Sweden and Japan with idiopathic dilated cardiomyopathy (DCM, n = 32), hypertrophic cardiomyopathy (HCM, n = 23), malignant essential hypertension (MEH, n = 11), malignant secondary hypertension (MSH, n = 10), and sera from healthy blood donors (HBD, n = 49) were tested. Sera from patients with DCM recognized the muscarinic receptor peptide in 38% of cases and the beta 1 adrenoceptor peptide in 31% of cases. In 50% of the positive patients, autoantibodies against both peptides coexisted as shown by competition experiments using both peptides as inhibitors. In HCM patients, there was a lower frequency of autoantibodies but with a higher but not significant predominance against the M2 peptide. No autoantibodies were detected in sera from patients with MEH or MSH. Autoantibodies against the M2 muscarinic receptors, affinity-purified from positive patients, displayed pharmacological activity as demonstrated by changes in the affinity and number of radioligand binding sites. In contrast, antibodies purified from positive HBD had no effect. These results confirm that autoantibodies displaying pharmacological activity against G-protein-coupled cardiovascular receptors are mainly restricted to patients with idiopathic dilated cardiomyopathy and that different autoantibody populations are responsible for the recognition of the different receptors.
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PMID:Autoantibodies against cardiac G-protein-coupled receptors define different populations with cardiomyopathies but not with hypertension. 802 Jan 88

Beta-blockers with less cardiodepressive effect than traditional nonselective beta(1+2)-blocking agents could be useful in the treatment of hypertension, provided the reduction in blood pressure was satisfactory. Epanolol, a selective beta 1-receptor blocker with intrinsic sympathomimetic activity, induced a fall in intraarterial pressure of 8% at rest sitting and 11% during 100 W bicycle exercise after the first dose of 200 mg in 12 patients with essential hypertension. Heart rate, stroke index, and cardiac index initially fell by 14%, 11%, and 23%, respectively. The total peripheral resistance index increased by 21% after 2 hours, and then reverted towards the pretreatment level. After 10 months of epanolol treatment (mean 300 mg/day), the reduction in arterial pressure was 5% at rest and 10% during exercise. Cardiac index and heart rate were still reduced 14-21%, while total peripheral resistance was unchanged or slightly increased (2-10%). Twenty-four hour ambulatory blood pressure was higher on epanolol (300 mg/day) than on atenolol (150 mg/day) treatment (137/97 vs. 128/91 mmHg). Thus, the achieved blood pressure reduction induced by epanolol was moderate, while other characteristics of beta-receptor blockade, in particular, the reduction of heart rate and cardiac output, were maintained. This suggests that the compound may be useful for other cardiovascular disorders, e.g., angina pectoris in patients without hypertension or cardiac arrhythmia.
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PMID:Modest antihypertensive effect of epanolol, a beta 1-selective receptor blocker with beta 1 agonist activity: an acute and long-term hemodynamic study at rest and during exercise and double crossover comparison with atenolol on ambulatory blood pressure. 809 25

dl-nebivolol is a new, chemically unique, selective beta 1-adrenoceptor antagonist, without sympathomimetic activity. In the present study, the antihypertensive and negative chronotropic effects of 5 and 10 mg once-daily nebivolol were compared to those of 50 and 100 mg once-daily atenolol in 25 white, male subjects with essential hypertension, using a double-blind, crossover design, and a parallel placebo-treated group of subjects (N = 7). 24 hours after dosing, sitting and standing diastolic and systolic blood pressures and heart rates (at rest and during submaximal exercise) were reduced to the same extent by nebivolol and atenolol. On a weight-for-weight basis, nebivolol is ten times more potent than atenolol. Nebivolol and atenolol also reduced 1-hour ambulatory plasma renin activity. Once-daily nebivolol is an effective antihypertensive beta-adrenoceptor antagonist.
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PMID:Comparison of antihypertensive and beta 1-adrenoceptor antagonist effect of nebivolol and atenolol in essential hypertension. 809 43

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

In a randomized double-blind crossover study in 42 patients with essential hypertension, the metabolic effects of a beta-adrenergic blocker with a pronounced beta 2-agonistic effect, dilevalol 400 mg x 1, were compared with those of metoprolol succinate 200 mg x 1. The effects of glucose metabolism were evaluated by the hyperinsulinemic euglycemic clamp technique and an intravenous glucose tolerance test (IVGTT). Insulin-mediated glucose disposal (M) and the insulin sensitivity index (M/I) increased by 19% (P = .011) and 10% (P = .27), respectively, during dilevalol treatment, but decreased by 10% (P = .15) and 22% (P = .0025), respectively, during metoprolol treatment, giving rise to significant differences between the two treatment regimens. Compared with dilevalol-treated patients, those treated with metoprolol showed increased plasma insulin values at the end of the IVGTT, but there was no difference in plasma glucose concentrations or glucose tolerance. Hemoglobin A1c (HbA1c) levels increased by 5.4% (P = .04) in the metoprolol group. Serum cholesterol, total serum and very-low-density lipoprotein (VLDL) triglycerides, and serum urate levels decreased significantly (by 6%, 22%, 29%, and 14%, respectively) during dilevalol treatment, and there was a significant difference between the effects of the two drugs on total, VLDL, and low-density lipoprotein (LDL) triglyceride and serum urate levels. These data demonstrate that a beta-blocker with a partial beta 2-agonist action differs in its metabolic effect profile from a selective beta 1-blocker and may offer advantages by improving glucose and lipid metabolism.
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PMID:Treatment with a beta-blocker with beta 2-agonism improves glucose and lipid metabolism in essential hypertension. 815 3

The primary physiological agents for adrenergic receptors are only two, epinephrine and norepinephrine, which have been used to differentiate alpha- and beta-adrenoceptors. The pharmacological properties can distinguish subtype alpha 1-, alpha 2-, beta 1- and beta 2-receptors. Recently additional subtypes have been characterized by radioligand binding techniques and molecular biological techniques. Molecular mechanisms of regulation as well as regulatory site of gene expression of alpha-adrenergic receptors has been extensively studied. In addition, the association analysis of alpha 2-adrenergic receptor gene RFLP in essential hypertension has been performed. Eventhough we could not find any association of an alpha 2 C10-Bsu36I RFLP with essential hypertension in Japan, the finding showed significant ethnic RFLP difference at the gene locus for alpha 2 C10. The association of alpha 2 adrenergic receptor RFLP with blood pressure has been also studied using F2 generations of SHR and WKY and Dahl salt sensitive rats and resistant rats. Further studies are now in progress to clarify the role of these alpha-adrenergic receptors in cardiovascular diseases.
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PMID:[Molecular biology of alpha-adrenergic receptor and essential hypertension]. 839 98

The objective of this study was to analyze the long-term hemodynamic effects of the calcium antagonist isradipine in mild hypertension compared with those of the beta 1-selective adrenoceptor antagonist atenolol, focusing in particular on the development of cardiac hypertrophy. Ten male patients with mild essential hypertension were entered into a double-blind crossover study. Examinations were carried out after 2 weeks of placebo run-in, and after 6 and 12 months of active treatment. Mean resting blood pressure was reduced from 115 +/- 12 mm Hg to 106 +/- 12 mm Hg with atenolol, and to 107 +/- 8 mm Hg with isradipine. The increase in the product of heart rate times blood pressure was significantly greater during isradipine treatment, as was the maximum exercise capacity. Left ventricular mass was increased from 228 +/- 36 g to 305 +/- 68 g with atenolol whereas it remained unchanged with isradipine (254 +/- 55 g). The results indicate that antihypertensive treatment with isradipine as monotherapy may prevent the development of left ventricular hypertrophy whereas treatment with atenolol as monotherapy does not appear to offer this possibility.
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PMID:Beneficial effect of isradipine on the development of left ventricular hypertrophy in mild hypertension. 846 41

The pathogenesis of hypertension associated with diabetes mellitus (DM) involves an interplay of hereditary and acquired mechanisms. A familial trait for essential hypertension appears to be a risk factor for the development of both hypertension and nephropathy in type I DM and coexists commonly with impaired insulin sensitivity, relative hyperinsulinemia, and dyslipidemia, which can already be detected before the appearance of hypertension, obesity, or upper abdominal redistribution of body fat. The latter finding helps explain the frequent development of hypertension as well as dyslipidemia and/or type II DM in given individuals. Obesity is an important factor promoting these complications. Type I or II DM but not uncomplicated essential hypertension is characteristically accompanied by excess body Na+. This abnormality complements a tendency toward vascular hyperreactivity and a presumably morphologic and functional vasculopathy, thereby promoting the pathogenesis of hypertension in diabetic patients. For the treatment of hypertension in diabetic patients, nonpharmacologic measures are indispensable. If drugs are needed, angiotensin-converting enzyme (ACE) inhibitors and some but not all calcium antagonists are the preferred agents. Monotherapy or a combination of these drug types allows effective blood pressure control in most diabetic patients without further metabolic impairment; ACE inhibitors even tend to improve glucose control. Ketanserin may be a potential alternative, and if a diuretic is also needed, the metabolically neutral indapamide is a reasonable choice. If these agents do not allow satisfactory blood pressure highly selective beta 1-blockers or alpha 1-blockers may be introduced as a second choice. In diabetic patients with nephropathy, effective antihypertensive therapy can reduce proteinuria and slow the progression of the nephropathy; ACE inhibitors may improve diabetic proteinuria even at unchanged systemic blood pressure levels. Unless diuretics are needed for reasons other than hypertension, the treatment of diabetic patients with thiazides or loop diuretics in conventional dosage should probably be avoided until clarification of their influence on prognosis. Nevertheless, whether and to what extent other agents and nonpharmacologic measures can modify the prognosis in diabetic patients is also unclear, and the approach to antihypertensive therapy is therefore still largely empiric.
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PMID:Pathogenesis and treatment of hypertension associated with diabetes mellitus. 848 Jun 21

The efficacy and tolerability of controlled-release metoprolol (metoprolol CR/ZOK), 100-200 mg, and atenolol, 50-100 mg, once daily was compared in Chinese patients with mild to moderate essential hypertension. The study was of a randomized, double-blind, two-way crossover design. The active treatment periods lasted 4 weeks each and were preceded by a 4-week placebo run-in period. The two double-blind phases were separated by a 2-week washout period on placebo. Blood pressures and heart rates were measured at rest in each 2-week visit and during exercise at the end of each treatment period. Twenty-four patients (M/F = 14/10) were valid for efficacy analysis. Their ages ranged from 39 to 68, with a mean of 53.5 years. The rest supine blood pressure and heart rate before active treatment was 160 +/- 15/106 +/- 6 mmHg and 75 +/- 14 beats/min (mean +/- SD), respectively. A responder was defined as exhibiting a supine diastolic blood pressure < or = 90 mmHg or a supine diastolic blood pressure reduction of at least 10% of the baseline level. Both agents had high response rate: 88% and 92% of all patients responded to metoprolol CR/ZOK and atenolol, respectively. Both active treatments considerably reduced resting systolic and diastolic blood pressures and heart rates as compared with baseline (p < 0.001), respectively. With controlled-release metoprolol, a more pronounced beta 1 blockade was obtained than with atenolol, which was expressed as a significant reduction in exercise-induced heart rate at the highest comparable workload compared with placebo (p < 0.05). These findings are compatible with those reported from western populations.
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PMID:A double-blind comparison of once-daily metoprolol controlled-release and atenolol in the treatment of Chinese patients with mild to moderate hypertension. 852 49


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