Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main objective of the Ambulatory Blood Pressure and Treatment of Hypertension (APTH) trial is to test the hypothesis that antihypertensive treatment based on ambulatory monitoring may be more beneficial than treatment guided by conventional sphygmomanometry. After a 2-month run-in period on single-blind placebo, hypertensive patients were randomized to two groups, one in which the target pressure was a sitting diastolic pressure from 80 through 89 mm Hg on conventional sphygmomanometry (conventional blood pressure [CBP] group), and one in which a daytime (from 10 to 20 h) diastolic pressure from 80 through 89 mm Hg had to be achieved (ambulatory blood pressure [ABP] group). After randomization all patients were started on lisinopril 10 mg/day. One month later lisinopril could be continued at 10 or 20 mg/day or discontinued depending on the attained blood pressure level. This article is an interim report on 207 patients followed for two months into the trial. At one month lisinopril was discontinued more frequently in the ABP than the CBP group (24 vs 9 patients, p = 0.004). Nevertheless at two months, blood pressure control was not significantly different in the two treatment groups. The baseline-adjusted differences in systolic pressure between the two treatment arms of the trial (ABP-CBP group) were +2.7 mm Hg (95% confidence interval [CI]): -2.9, +8.3) for the conventional pressure, +0.4 mm Hg (CI: -4.3, +5.1) for the 24 h pressure, -0.1 mm Hg (CI: -5.1, +4.8) for the daytime pressure and -0.7 mm Hg (CI: -6.7, +5.4) for the night-time pressure. The corresponding differences in diastolic pressure were -1.3 mm Hg (CI: -4, +1.4), +0.1 mm Hg (CI: -3, +3.1), -1.1 mmgH (CI: -4.4, +2.1) and +0.3 mm Hg (CI: -3.7, +4.3), respectively. Thus, the present findings do not refute the APTH research hypothesis. In terms of blood pressure control and the number of patients remaining on antihypertensive drugs, treatment based on ambulatory recordings may be preferable to treatment guided by conventional sphygmomanometry.
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PMID:Treatment of hypertensive patients according to the conventional or ambulatory pressure: a progress report on the APTH trial. APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension. 881 7

Poor left-ventricular function, hypertension, and left-ventricular hypertrophy in patients with coronary artery disease (CAD) undergoing coronary artery bypass grafting (CABG) are associated with increased operative risks. Between June 1994 and March 1996, 33 patients undergoing CABG, were randomized into 2 groups. One group (IABP group, n = 19) received IABP treatment on average for 2 hours prior to CPB, the other group (control group, n = 14) had no preoperative IABP, Cardiac performance was measured pre- and postoperatively by Swan-Ganz catheter. Mean age was 65 years and 90% were men. All patients had a preoperative LVEF < or = 40% (mean 32.6 +/- 11.1%), 3-vessel disease, established hypertension (WHO criteria), and LV hypertrophy (ventricular mass > or = 136 g/m2 [men] or > or = 110 g/m2 [women]). Ischemia time was similar in both groups while CPB-time was shorter in the IABP group, p < 0.05. There were no hospital deaths in the IABP group, but 3 in the control group suffered postoperative low cardiac output. Nine patients (64%) in the control group required IABP support postoperatively, but only 20% of the patients in the IABP group had a shorter ICU stay, 2.4 +/- 0.9 vs. 3.4 +/- 1.1 days, p < 0.01. Cardiac index increased significantly in the IABP group prior to CPB and was higher compared to control, p < 0.001. Five min after CBP cardiac index was higher in the IABP group than in the control group, p = 0.013, and continued to increase thereafter, while no further improvement was observed in controls. Preoperative IABP treatment in hypertensive patients with CAD, low LVEF and LV hypertrophy who are undergoing CABG is beneficial. An improved cardiac performance pre- and postoperatively was associated with a lower rate of hospital mortality and less postoperative morbidity, as well as shorter ICU stay. The treatment is cost-beneficial.
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PMID:The effect of preoperative intra-aortic balloon pump support in patients with coronary artery disease, poor left-ventricular function (LVEF < 40%), and hypertensive LV hypertrophy. 917 20

Peroxisome proliferator-activated receptors (PPARs) belongs to the nuclear hormone receptor superfamily. So far three different subtypes of PPAR (alpha, gamma, and delta (beta)) have been identified in amphibians, chicken, rodents and man. These receptors are transcription factors that control the beta-oxidation and transport pathways of fatty acids and adipocyte differentiation containing fatty acid synthesis under the modification of PPAR activation with CBP and its analogs. Thus, PPARs play an important role in lipid metabolism. Furthermore, altered fatty acid levels are associated with obesity, diabetes, hypertension and atherosclerosis, so PPARs may serve as molecular sensors in these metabolic disorders.
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PMID:[Lipid metabolism related nuclear receptor--the structure, function, expression and classification of peroxisome proliferation-activated receptor (PPAR)]. 970 44

This prospective population study investigated in a random sample of 692 subjects (age 20-83 years) how changing environmental exposure to cadmium influenced blood pressure (BP) and the incidence of hypertension. At baseline (1985 to 1989; participation rate, 78%) and follow-up (1991 to 1995; re-examination rate, 81%), blood pressure was measured by conventional sphygmomanometry (CBP; 15 readings in total) and, at follow-up, also by 24-h ambulatory blood pressure monitoring (ABP). Systolic/diastolic CBP at baseline averaged 128.4/77.3 mm Hg. At baseline, blood cadmium concentration (B-Cd) and urinary cadmium excretion (U-Cd) averaged (geometric means) 11.1 nmol/L and 10.2 nmol/24 h. Over 5.2 years (median follow-up), B-Cd fell by 29.6% and U-Cd by 15.2%. B-Cd fell less in subjects living closer to three zinc smelters and in premenopausal women. During follow-up, systolic CBP decreased by 2.2 mm Hg in men and remained unchanged in women, and diastolic CBP increased by 1.8 mm Hg in both sexes. No relationship could be demonstrated between the secular trends in CBP and B-Cd or U-Cd or between B-Cd or U-Cd at baseline and the incidence of hypertension. In addition, in cross-sectional analyses involving the average of all available CBP measurements in each participant or 24-h ABP at follow-up (mean, 119.1/71.4 mm Hg), blood pressure was not correlated with B-Cd or U-Cd. In conclusion, environmental exposure to cadmium was not associated with higher CBP or 24-h ABP or with increased risk for hypertension. The lesser fall in B-Cd in the residents living closer to the zinc smelters or in premenopausal women underscores the necessity to sanitize cadmium-polluted areas and to systematically reinforce the preventive measures to be adopted by exposed communities to reduce cadmium uptake.
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PMID:Exposure to cadmium and conventional and ambulatory blood pressures in a prospective population study. Public Health and Environmental Exposure to Cadmium Study Group. 1070 14

This study investigated the differences in the effect of an angiotensin converting enzyme inhibitor (ACEI) compared with an angiotensin receptor blocker (ARB) on blood pressure (BP) and pulse pressure (PP) measured in the clinic (CBP and CPP, respectively), at home (HBP, HPP) and with ambulatory monitoring (ABP, APP). Twenty-seven hypertensive patients were randomised to receive lisinopril (20 mg) or losartan (50 mg) for 5 weeks, and were subsequently crossed-over to the alternative treatment for a second 5-week period. Measurements of CBP, 24-h ABP and 5-days HBP were performed before randomisation and at the end of each treatment period. All measurement methods showed that lisinopril was more effective than losartan in reducing BP. However, the difference between the two drugs was demonstrated with greater precision using HBP (P<0.001) than 24-h ABP (P<0.01), whereas the poorest precision for demonstrating this difference was provided by CBP (P<0.05). Lisinopril was also found more effective than losartan in reducing HPP (P=0.01) and 24-h APP (P=0.03) whereas no such a difference was detected using measurements of CPP. It was concluded that the antihypertensive drugs may differ in their effects not only on BP, but also on PP. HBP monitoring appears to be as reliable as 24-h ABP monitoring in detecting differences in the effect of drugs on both BP and PP. Clinic measurements seem to be the least reliable method, particularly in the detection of differences in PP.
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PMID:Assessment of drug effects on blood pressure and pulse pressure using clinic, home and ambulatory measurements. 1242 Jan 98

Over last two decades ABPM has evolved from a research device to an established and valuable clinical tool for BP evaluation. More than 10 yrs ago ABPM was introduced to pediatrics and since that time, its importance has been increasing in the management of hypertension in children and adolescents. This review summarizes the information gathered from the studies of ABPM in adult and pediatric patients with renal transplants. We will review the importance of hypertension in this patient subset, discuss the advantage of ABPM over CBP and focus on specific abnormalities and clinical significance of ABPM in renal transplant recipients.
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PMID:Ambulatory blood pressure monitoring in pediatric renal transplantation. 1265 47

In people aged >80 years, the so-called very elderly, there is uncertainty about the relation between hypertension and cardiovascular morbidity. The aims of this study were to investigate whether hypertension in people aged >80 years is associated with target-organ damage, over and above the effects of age, and to determine whether ambulatory blood pressure monitoring (ABPM) could improve on conventional blood pressure monitoring (CBPM) in predicting target-organ damage. Investigations included echocardiographic measurement of left ventricular mass index (LVMI), brain magnetic resonance imaging assessment of periventricular hyperintensity (PVH), urinary albumin-creatinine ratio (ACR), aortic pulse wave velocity (PWV), and 24-hour ABPM. Forty-three subjects, at a mean age 84.3 years, were studied, 22 normotensive (NT) and 21 hypertensive (HT). CBP was 184/89 and 145/76 mm Hg in the HT and NT groups, respectively. In men, LVMI was significantly greater in HT subjects, 157+/-37 vs 123+/-15 g/m2 in NT subjects (P<0.05). In women, LVMI was similar in both groups. Urinary ACR was greater in HT than in NT subjects (log ACR, 1.21+/-0.50 vs 0.95+/-0.23; P<0.05). Cerebral PVH grade was higher in the HT subjects (2.6+/-0.8 vs 2.2+/-0.9), although this difference was not significant. Aortic PWV did not differ between the 2 groups. ABPM was positively associated with urinary ACR and cerebral PVH, independent of its correlation with CBPM. In advanced old age, HT is associated with evidence of target-organ damage. ABPM can improve on CBPM in predicting very elderly subjects with HT target-organ damage.
Hypertension 2003 Aug
PMID:Hypertensive target-organ damage in the very elderly. 1286 Aug 37

Peroxisome proliferator-activated receptor gamma (PPARgamma) is an important therapeutic drug target against several diseases such as diabetes, inflammation, dyslipidemia, hypertension, and cancer. Ligand binding to PPARgamma is responsible for controlling the biological functions, and developing new technology to measure ligand-PPARgamma binding is significant for both the function study of the receptor and ligand discovery. In this study, we exploited an efficient approach for the discovery of PPARgamma agonist and antagonist via a yeast two-hybrid system based on the fact that PPARgamma interacts with the coactivator CBP (CREP-binding protein) ligand-dependently. We employed the MEL1 reporter gene instead of the traditionally used LacZ gene to evaluate the protein-protein interactions by conducting a convenient alpha-galactosidase assay in the yeast strain AH109 with genes of PPARgamma-LBD (ligand-binding domain) and CBP N terminus introduced. With this built screening platform, the EC(50) values of the PPARgamma agonists rosiglitazone, troglitazone, pioglitazone, indomethacin, 15-deoxy-Delta12,14-prostaglandin J(2) (15d-PGJ(2)), and GI262570 were investigated, and the quantitatively antagonistic effect by IC(50) of the PPARgamma typical antagonist GW9662 on the rosiglitazone agonistic activity was fully examined. The reliability of this presented system evaluated by the comparable agreement of EC(50) and IC(50) values for the test compounds with the reported ones indicated that this yeast two-hybrid-based approach is powerful for PPARgamma agonist and antagonist screening. In addition, because this screening system is designed for use in a microtiter plate format where numerous chemicals could be readily screened, it is hoped that this yeast two-hybrid screening approach may be adaptable for high-throughput settings.
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PMID:A yeast two-hybrid technology-based system for the discovery of PPARgamma agonist and antagonist. 1555 64

The control of high blood pressure (BP) after awakening in the morning (morning hypertension) as determined by home BP (HBP), as well as BP control throughout the day, may prevent diabetic vascular complications. We examined the effect of an alpha-adrenergic blocker (doxazosin) on BP measurements taken by HBP after awakening and during clinic visits (CBP) in 50 patients with type-2 diabetes and morning hypertension. We evaluated the urinary albumin excretion rate as an indicator of nephropathy. Doxazosin was taken orally once at bedtime for 1 to 3 months. The mean (+/- SD) dose was 2.9 +/- 2.1 mg/day (1 to 8 mg/day). The BP was measured monthly at the clinic during the day and at home after awakening in the morning. In this short-term trial (2.8 +/- 0.4 months), the systolic HBP decreased significantly from 164 +/- 17 mmHg before treatment to 146 +/- 19 mmHg after treatment, and the diastolic HBP decreased significantly from 85 +/- 14 mmHg before treatment to 80 +/- 9 mmHg after treatment. The systolic, but not the diastolic CBP, decreased significantly after treatment. There was no significant difference in the systolic or diastolic values between the HBP and the CBP after treatment. The percentage change in the systolic HBP after treatment was three times greater than for the systolic CBP. The median (interquartile) urinary albumin excretion rate decreased significantly (P < 0.001) from 62 (25-203) mg/g creatinine before treatment to 19 (9-76) mg/g creatinine after treatment. On multiple regression analysis, the decrease in the systolic HBP with treatment positively correlated with the reduction in urinary excretion of albumin. The control of morning hypertension reduced the albuminuria found in both untreated and treated hypertensive patients with type-2 diabetes. Bedtime administration of doxazosin appears to be safe and effective in reducing morning hypertension as measured by HBP. This finding also demonstrates that HBP taken in the morning has a stronger predictive power for the albuminuria level than does CBP.
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PMID:The bedtime administration of doxazosin controls morning hypertension and albuminuria in patients with type-2 diabetes: evaluation using home-based blood pressure measurements. 1592 Oct 73

The peroxisome proliferator-activated receptor gamma (PPARgamma) is an important therapeutic drug target for several conditions, including diabetes, inflammation, dyslipidemia, hypertension, and cancer. It is shown that an antagonist or partial agonist of PPARgamma has attractive potential applications in the discovery of novel antidiabetic agents that may retain efficacious insulin-sensitizing properties and minimize potential side effects. In this work, the dipeptide H-Trp-Glu-OH (G3335) was discovered to be a novel PPARgamma antagonist. Biacore 3000 results based on the surface plasmon resonance (SPR) technique showed that G3335 exhibits a highly specific binding affinity against PPARgamma (K(D) = 8.34 microM) and is able to block rosiglitazone, a potent PPARgamma agonist, in the stimulation of the interaction between the PPARgamma ligand-binding domain (LBD) and RXRalpha-LBD. Yeast two-hybrid assays demonstrated that G3335 exhibits strong antagonistic activity (IC50 = 8.67 microM) in perturbing rosiglitazone in the promotion of the PPARgamma-LBD-CBP interaction. Moreover, in transactivation assays, G3335 was further confirmed as an antagonist of PPARgamma in that G3335 could competitively bind to PPARgamma against 0.1 microM rosiglitazone to repress reporter-gene expression with an IC50 value of 31.9 muM. In addition, homology modeling and molecular-docking analyses were performed to investigate the binding mode of PPARgamma-LBD with G3335 at the atomic level. The results suggested that residues Cys285, Arg288, Ser289, and His449 in PPARgamma play vital roles in PPARgamma-LBD-G3335 binding. The significance of Cys285 for PPARgamma-LBD-G3335 interaction was further demonstrated by PPARgamma point mutation (PPARgamma-LBD-Cys285Ala). It is hoped our current work will provide a powerful approach for the discovery of PPARgamma antagonists, and that G3335 might be developed as a possible lead compound in diabetes research.
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PMID:The dipeptide H-Trp-Glu-OH shows highly antagonistic activity against PPARgamma: bioassay with molecular modeling simulation. 1631 83


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