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)

Beta-adrenergic receptor-blocking agents are commonly used for treatment of hypertension, angina pectoris and arrhythmias and as secondary prevention after myocardial infarction. The modest protection against myocardial infarction conferred by these compounds in primary-preventive studies has suggested that beneficial effects of beta-blockade are counteracted by known adverse influences on lipid and glucose metabolism. As most beta-blockers increase plasma triglycerides and decrease the high density lipoprotein (HDL) cholesterol concentration, a randomized, double-blind, cross-over study was conducted to evaluate whether a 12-week treatment with metoprolol (100 mg o.d.) or placebo affected the metabolism of postprandial triglyceride-rich lipoproteins in 15 middle-aged men with a modestly increased cardiovascular risk. Metoprolol treatment significantly increased the postprandial responses of very low density lipoprotein (VLDL) and VLDL remnants to a mixed meal-type of oral fat tolerance test. The effect was particularly prominent for larger (Svedberg flotation rate (Sf) > 400 and Sf 60-400) particle species (P < 0.001 in repeated measures ANOVA), whereas the smaller (Sf 20-60) particles were less affected (P < 0.05). The changes in the postprandial responses of the different VLDL species were mainly related to an effect on the fasting plasma concentrations, with limited or no influences on VLDL catabolism during the postprandial state. In contrast, metoprolol treatment did not significantly influence the postprandial responses of chylomicrons and chylomicron remnants. Notably, the enhanced fasting and postprandial triglyceridaemia during metoprolol treatment was neither accompanied by a rise in fasting or postprandial free fatty acid concentrations, nor by alterations of the glucose and insulin responses to a standard oral glucose challenge. The ensuing shift in the LDL particle size distribution towards smaller particles was limited (fraction small LDL: metoprolol 22.8 +/- 15.7% versus placebo 19.3 +/- 15.0%, P < 0.05). In conclusion, metoprolol treatment primarily enhances fasting and postprandial triglyceridaemia in middle-aged men by increasing the basal hepatic production of VLDL.
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PMID:Effects of a cardioselective beta-blocker on postprandial triglyceride-rich lipoproteins, low density lipoprotein particle size and glucose-insulin homeostasis in middle-aged men with modestly increased cardiovascular risk. 962 82

To evaluate the relative effect of hypertension and plasma triglycerides on intralymphocyte magnesium we measured ionized intralymphocyte magnesium (Mg(i)) concentration by means of a fluorimetric method based on the dye Furaptra in 4 groups of subjects: 18 normotensive normotriglyceridemic controls (NTNC), 9 hypertriglyceridemic normotensive patients (HTN), 8 hypertriglyceridemic essential hypertensive patients (HTEH), 17 normotriglyceridemic essential hypertensive patients (NTEH). Hypercholesterolemic, diabetic patients and alcoholics were excluded from the study. Mg(i) was found to be statistically reduced (ANOVA test F=10.41, P=0.0001) in both HTN and HTEH (M+/- SD, HTN: 0.235 +/- 0.01, HTEH: 0.236 +/- 0.01 mmol/l) as compared to both NTNC and NTEH (M +/- SD, NTNC: 0.294 +/- 0.008, NTEH: 0.297 +/- 0.009 mmol/l). A statistically significant negative correlation was found in the population as a whole between Mg(i) and plasma triglycerides (n=52, R= -541, P=0.00004). Our data suggest that hypertriglyceridemia per se and possibly the so-called plurimetabolic syndrome is characterized by low intralymphocyte free magnesium.
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PMID:Intralymphocyte free magnesium and plasma triglycerides. 962 82

Lifestyle behaviors are thought to be guided by cognitive or mental representations that function to structure knowledge related to behaviors and goals. The Lifestyle Hypertension Cognitive Representations (LHCR) scale was developed to measure cognitions about hypertension-related behaviors on three cognitive dimensions. Items were derived from a literature and content analysis of qualitative data from 124 hypertensive patients. The three dimensions based on cognitive research generated subscales for perceptions (recognition), preferences (importance), and possibilities (future usefulness). Internal consistency reliability was adequate with alpha coefficients near .80 for composite and subscales in two independent culturally diverse samples. The total-to-total correlation with a related construct was low. One-way ANOVA demonstrated the expected results for known group differences by severity of blood pressure state for the composite, perceptions and possibilities subscales of the LHCR. Multiple regression revealed that the perceptions and possibilities subscales interacted to predict diastolic blood pressure. Together with socio-demographic variables explained the variance for a total of 25%. Further work is indicated to determine the instrument's usefulness as a basis for interventions to reduce blood pressure.
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PMID:Reliability and validity of the Lifestyle Hypertension Cognitive Representations scale. 967 64

To investigate the relationship between polymorphisms of the angiotensin-converting enzyme (ACE) and the angiotensin II type 1 receptor (AT1R) genes and structural phenotypes of arteries, we studied a cohort of 340 subjects (aged 49+/-12 years) without evidence of cardiovascular disease and who had never been treated previously with any cardiovascular treatments. Structural phenotypes (wall thickness and internal diameter) were evaluated for the common carotid and the radial arteries using high-resolution echo-tracking devices (NIUS-02 and Wall Track System). The influence of ACE insertion/deletion (I/D) and AT1R A/C1166 polymorphism genotypes on structural parameters was tested by ANOVA and logistic regression analysis. For the radial artery, mean wall thickness among subjects according to the ACE I/D or AT1R A/C1166 genotypes was not different. This lack of association persisted in a logistic regression analysis or when the comparison was restricted to a subgroup of subjects potentially at high genetic risk (DD and CC or AC) compared with subjects at low genetic risk (AA and II or ID). Also, no association was observed between the carotid artery intima-media thickness and the 2 polymorphisms. In conclusion, the ACE I/D and the AT1R A/C1166 gene polymorphisms are not markers of vascular hypertrophy in subjects with no evidence of cardiovascular disease. These results suggest that these gene polymorphisms have an undetectable role in the geometry of the radial and carotid arteries compared with usual determinants such as blood pressure and age.
Hypertension 1998 Sep
PMID:Lack of association between renin-angiotensin system, gene polymorphisms, and wall thickness of the radial and carotid arteries. 974 Jun 30

To determine sleep effects on baro- and ventilatory responses to transient chemo- and barostimulation in African-Americans and Caucasians, 26 nonobese normotensive young subjects (13 African-Americans and 13 Caucasians) were studied awake and in non-rapid-eye movement (NREM) and rapid-eye-movement sleep during induced transient hypoxemia (N2), hypertension (phenylephrine, PE), and concomitant hypoxemia and hypertension (N2 + PE). Arterial blood pressure was recorded by plethysmographic volume clamp, minute ventilation by pneumotachograph, and arterial O2 saturation by pulse oximeter. For all subjects, chronotropic baroresponse (Deltapulse interval/Deltasystolic blood pressure, where Delta is change) increased with NREM sleep (P = 0.007). Baroresponse slope was greater in Caucasians than in African-Americans (ANOVA, P = 0.02). Hypoxemic ventilatory response (Deltaminute ventilation/Deltaarterial O2 saturation) was greater in African-Americans than in Caucasians in NREM sleep (P = 0.01), as was hypoxemic attenuation of baroresponse (N2 + PE, P = 0.03). These data suggest sleep-related differences in arterial chemo- and baroreceptor responses in normal young African-Americans and Caucasians, which may have implications concerning development of systemic hypertension.
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PMID:Chemo- and baroresponses differ in African-Americans and Caucasians in sleep. 976 Mar 35

The concomitant effects of infusions of catecholamines on cerebral blood flow (CBF), intracranial pressure (ICP), arterio-venous oxygen content difference (AVDO2), and cerebral oxygen utilization (COU) were prospectively studied in an intact cerebral autoregulatory model. Epinephrine, norepinephrine and dopamine were infused at doses used in clinical practice in awake, chronically catheterized sheep (n = 5). Mean arterial pressure (MAP), CBF and ICP were measured continuously, COU was expressed as delta CBF x AVDO2. All 3 drugs significantly increased MAP in a dose dependent manner. Norepinephrine and epinephrine had no significant effects on ICP, CBF, AVDO2 or COU at infusions of 0-60 micrograms/min. Infusions of dopamine from 0-60 micrograms/kg/min resulted in statistically significant increases in ICP (+34.5 +/- 3.7 to +97.2 +/- 6.8) and CBF (+13.3 +/- 3.2 to +52.6 +/- 24.3) (% change baseline +/- SEM, 95% CI, ANOVA), reduction in AVDO2 (3.54 +/- 0.2. to 2.69 +/- 0.2 mg%) and a biphasic response in COU. In the intact physiological model, induced hypertension by epinephrine and norepinephrine is not associated with global changes in CBF, ICP or COU which remain constant. At equivalent doses, dopamine causes cerebral hyperaemia, increased ICP and increased global cerebral oxygen utilization.
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PMID:A comparison of the effects of norepinephrine, epinephrine, and dopamine on cerebral blood flow and oxygen utilisation. 977 32

Increased plasma renin activity (PRA) has been associated with an increased risk of myocardial infarction (MI), whereas angiotensin-converting enzyme (ACE) inhibition appears to reduce the risk of recurrent MI in patients with left ventricular dysfunction. These observations may be partially explained by an interaction between the renin-angiotensin system (RAS) and fibrinolytic system. To test this hypothesis, we examined the effect of salt depletion on tissue-type plasminogen activator (tPA) antigen and plasminogen activator inhibitor-1 (PAI-1) activity and antigen in normotensive subjects in the presence and absence of quinapril (40 mg BID). Under low (10 mmol/d) and high (200 mmol/d) salt conditions there was significant diurnal variation in PAI-1 antigen and activity and tPA antigen. Morning (8 AM through 2 PM) PAI-1 antigen levels were significantly higher during low salt intake compared with high salt intake conditions (ANOVA, F=5.8, P=0.048). PAI-1 antigen correlated with aldosterone (r=0.56, P<10(-7)) during low salt intake. ACE inhibition significantly decreased 24-hour (ANOVA for 24 hours, F=6. 7, P=0.04) and morning (F=24, P=0.002) PAI-1 antigen and PAI-1 activity (F=6.48, P=0.038) but did not alter tPA antigen. Thus, the mean morning PAI-1 antigen concentration was significantly higher during low salt intake than during either high salt intake or low salt intake and concomitant ACE inhibition (22.7+/-4.6 versus 16. 1+/-3.3 and 16.3+/-3.7 ng/mL, respectively; P<0.05). This study provides evidence of a direct functional link between the RAS and fibrinolytic system in humans. The data suggest that ACE inhibition has the potential to reduce the incidence of thrombotic cardiovascular events by blunting the morning peak in PAI-1.
Hypertension 1998 Dec
PMID:Effect of activation and inhibition of the renin-angiotensin system on plasma PAI-1. 985 58

-Essential hypertensives display enhanced signal transduction through pertussis toxin-sensitive G proteins. The T allele of a C825T variant in exon 10 of the G protein beta3 subunit gene (GNB3) induces formation of a splice variant (Gbeta3-s) with enhanced activity. The T allele of GNB3 was shown recently to be associated with hypertension in unselected German patients (frequency=0.31 versus 0.25 in control). To confirm and extend this finding in a different setting, we performed an association study in Australian white hypertensives. This involved an extensively examined cohort of 110 hypertensives, each of whom were the offspring of 2 hypertensive parents, and 189 normotensives whose parents were both normotensive beyond age 50 years. Genotyping was performed by polymerase chain reaction and digestion with BseDI, which either cut (C allele) or did not cut (T allele) the 268-bp polymerase chain reaction product. T allele frequency in the hypertensive group was 0.43 compared with 0.25 in the normotensive group (chi2=22; P=0.00002; odds ratio=2.3; 95% CI=1.7 to 3.3). The T allele tracked with higher pretreatment blood pressure: diastolic=105+/-7, 109+/-16, and 128+/-28 mm Hg (mean+/-SD) for CC, CT, and TT, respectively (P=0.001 by 1-way ANOVA). Blood pressures were higher in female hypertensives with a T allele (P=0.006 for systolic and 0.0003 for diastolic by ANOVA) than they were in male hypertensives. In conclusion, the present study of a group with strong family history supports a role for a genetically determined, physiologically active splice variant of the G protein beta3 subunit gene in the causation of essential hypertension.
Hypertension 1998 Dec
PMID:G-protein beta3 subunit gene (GNB3) variant in causation of essential hypertension. 985 80

We carried out a total genome screen in the Sabra rat model of hypertension to detect salt-susceptibility genes. We previously reported in male animals the presence of 2 major quantitative trait loci (QTLs) on chromosome 1 that together accounted for most of the difference in the blood pressure (BP) response to salt loading between Sabra hypertension-prone rats (SBH/y) and Sabra hypertension-resistant rats (SBN/y). In females, we reported on 2 major QTLs on chromosomes 1 and 17 that together accounted for only two thirds of the difference in the BP response between the strains. On the basis of phenotypic patterns of inheritance in reciprocal F2 crosses, we proposed a role of the X chromosome. We therefore continued the search for the missing QTL in females that would account for the remaining difference in the BP response between the 2 strains using newly developed microsatellite markers and focusing on chromosome X. We screened an F2 cross, consisting of 371 females and 336 males, using 19 polymorphic chromosome X microsatellite markers. We analyzed the averages of BP by genotype using ANOVA and the individual data using MAPMAKER/QTL. In female F2 progeny, we identified a segment on chromosome X that spans over 33.4 cM and shows significant cosegregation (P<0.001) of 14 microsatellite markers (demarcated by DXRat4 and DXMgh10) with systolic BP after salt loading. This segment has 2 apparent peaks at DXRat4 and DXRat13, with a BP effect of 14 mm Hg for each. Multipoint linkage analysis with a free model detected 3 peaks (logarithm of the odds ratio [LOD] score >4.3) within the same chromosomal segment: One between DXMgh9 and DXMit4 (LOD 4.9; 6.1% of variance), a second between DXMgh12 and DXRat8 (LOD 5.2; 7.2% of variance), and a third between DXRat2 and DXRat4 (LOD 5.8; 7.5% of variance). On the basis of these findings and until congenic strains become available, our working assumption is that within chromosome X, 1 to 3 genetic loci contribute importantly to the BP response of female Sabra rats to salt. In male F2 progeny, we detected no significant cosegregation of any region on chromosome X with the BP response to salt loading. We conclude that in the female rat, salt susceptibility is mediated by 3 to 5 gene loci on chromosomes 1, 17, and X, whereas in the male rat, the X chromosome does not affect the BP response to salt.
Hypertension 1999 Jan
PMID:Role of chromosome X in the Sabra rat model of salt-sensitive hypertension. 993 Nov 14

off aim of our study was to evaluate the effect of antihypertensive treatment on flow-mediated dilation (FMD)of a large artery, a noninvasive estimate of endothelial function, in hypertensive patients. In 78 consecutive hypertensive patients (40%men; age range, 42 to 67 years) we measured by a high-resolution ultrasound system the changes of brachial artery diameter during reactive hyperemia and after sublingual glyceryl trinitrate (400 microg); brachial artery flow velocity was measured by pulsed Doppler. The results of 2 studies are reported. In the first study, this procedure was repeated in 58 patients after 6 and 12 months of treatment with a combination of antihypertensive drugs; in a second study, the FMD was assessed in 20 patients after 2 months of monotherapy with either nifedipine or hydrochlorothiazide. In the first study, FMD was significantly increased after treatment compared with baseline (from 3.1+/-3% at baseline to 6.5+/-4.5% at 6 months and to 8.12+/-4. 6% at 12 months; P<0.001 by ANOVA), concomitant with blood pressure reduction (from 162+/-24/102+/-13 mm Hg to 141+/-12/89+/-6 mm Hg and to 141+/-9/89+/-6 mm Hg; P<0.001 by ANOVA); significant changes of endothelium-independent dilation were also observed, but only after 12 months of treatment (from 14.2+/-4.8 at baseline to 15.5+/-4.7 at 6 months and 16.8+/-5.9% at 12 months; P=0.03 by ANOVA). In the second study, FMD was significantly increased during nifedipine treatment as compared with baseline (from 5+/-6.18% at baseline to 9. 45+/-3.94%, P<0.001), while it did not change in patients receiving hydrochlorothiazide (from 5.15+/-5.28% at baseline to 4.69+/-4.34%, NS). No significant changes of endothelium-independent dilation were observed with both drugs (from 17.10+/-2.4% to 18.14+/-3.76% and from 18.73+/-4.07% to 17.46+/-4.27% during nifedipine and hydrochlorothiazide, respectively, NS). Thus, in essential hypertensive patients an improvement of the impaired FMD of the brachial artery, evaluated by noninvasive ultrasound, may be observed after long-term, effective blood pressure reduction, suggesting a beneficial effect of antihypertensive treatment on endothelial function. It seems that beyond blood pressure control, a calcium antagonist may be more effective than a diuretic in this respect.
Hypertension 1999 Jan
PMID:Effect of treatment on flow-dependent vasodilation of the brachial artery in essential hypertension. 993 Nov 68


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