ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo investigate the role of hypercholesterolemia in the regulation of blood pressure.Subjects and methodsWe compared blood pressure responses to arithmetic stress and hand-grip tests in normotensive patients with hypercholesterolemian= 15) and a mean (± SEM) age of 49 ± 3 years, and normal cholesterolemic controls (n= 22) aged 48 ± 1 years. Blood pressure and heart rate were measured throughout the tests. We examined the intracellular Ca2+concentration in platelets with or without low-density-lipoprotein stimulation (2.9 nmol/l, 10 mg/ml). The plasma nitrite plus nitrate and cyclic GMP were determined before and at the end of each test to evaluate nitric oxide production and activity.ResultsBoth tests showed that systolic/diastolic blood pressure was higher in the hypercholesterolemic patients than in the normal controls (stress test: 139 ± 3/91 ± 4 versus 127 ± 2/80 ± 3 mmHg,P< 0.01/P< 0.05; handgrip test: 164 ± 5/106 ± 5 versus 144 ± 3/88 ± 3 mmHg,P< 0.01/P< 0.01). The intracellular Ca2+concentration in platelets and the increase in response to low-densitylipoprotein stimulation were higher in the hypercholesterolemic patients (without stimulation: 72 ± 3 versus 64 ± 3 nmol/l,P< 0.01; with 2.9 nmol/l stimulation: 145 ± 21 versus 89 ± 6 nmol/l,P< 0.01). The increase in Ca2+in response to 2.9 nmol/ml stimulation with lowdensity lipoprotein was positively related to the increase in mean blood pressure in response to the stress test (r= 0.56,P< 0.002). Nitric oxide production appeared to be increased in the hypercholesterolemic patients (65 ± 5 versus 51 ± 4 mmol/l,P< 0.05), and was not affected significantly by the tests. In contrast, cyclic GMP was lower in the patients and was increased significantly in the normal controls by the hand-grip test (P< 0.05). As a result, plasma cyclic GMP was lower in the patients (1.9 ± 0.2 versus 2.5 ± 0.1 nmol/l,P< 0.01). The ratio of plasma cyclic GMP to nitric oxide was also lower in the hypercholesterolemic patients at rest (P< 0.05), and at the end of the mental stress (P< 0.02) and hand-grip (P< 0.001) tests.ConclusionsPatients with hypercholesterolemia showed an exaggerated blood pressure response to both mental stress and exercise, even if resting blood pressure was normal. Increases in the intracellular Ca2+concentration can contribute to these excessive responses. A disproportionately lower level of cyclic GMP to nitric oxide in plasma may also be involved in these abnormal responses.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe association between cardiovascular disease risk and job strain (high-demand, low-control work) may be mediated by heightened physiological stress responsivity. We hypothesized that high levels of job strain lead to increased cardiovascular responses to uncontrollable but not controllable stressors. Associations between job strain and blood pressure reductions after the working day (unwinding) were also assessed.DesignAssessment of cardiovascular responses to standardized behavioral tasks, and ambulatory monitoring of blood pressure and heart rate during a working day and evening.ParticipantsWe studied 162 school teachers (60 men, 102 women) selected from a larger survey as experiencing high or low job strain.MethodsBlood pressure, heart rate and electrodermal responses to an externally paced (uncontrollable) task and a self-paced (controllable) task were assessed. Blood pressure was monitored using ambulatory apparatus from 0900 to 2230 h on a working day.ResultsThe groups of subjects with high and low job strain did not differ in demographic factors, body mass or resting cardiovascular activity. Blood pressure reactions to the uncontrollable task were greater in high than low job-strain groups, but responses to the controllable task were not significantly different between groups. Systolic and diastolic blood pressure did not differ between groups over the working day, but decreased to a greater extent in the evening in subjects with low job strain.ConclusionsJob strain is associated with a heightened blood pressure response to uncontrollable but not controllable tasks. The failure of subjects with high job strain to show reduced blood pressure in the evening may be a manifestation of chronic allostatic load.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveAdrenomedullin is a newly discovered 52 amino acid peptide that has a potent vasodilating action. The present study was undertaken to investigate the role of adrenomedullin in the regulation of membrane fluidity of erythrocytes in patients with essential hypertension.Methods and resultsWe used an electron paramagnetic resonance and spin-labeling method. Adrenomedullin significantly decreased the order parameter for 5-nitroxide stearate and peak height ratio for 16-nitroxide stearate obtained from electron paramagnetic resonance spectra of erythrocyte membranes in normotensive volunteers (mean ± SEM order parameter value: control, 0.718 ± 0.003,n= 16; adrenomedullin at 10−9mol/l, 0.692 ± 0.004,n= 16,P< 0.05; adrenomedullin at 10−8mol/l, 0.690 ± 0.004,n= 16,P< 0.05; adrenomedullin at 10−7mol/l, 0.683 ± 0.004,n= 16,P< 0.05). The findings showed that adrenomedullin increased the membrane fluidity of erythrocytes. In addition, the effect of adrenomedullin was significantly potentiated by prostaglandin E1and dibutyryl cyclic AMP. In contrast, the calcium ionophore A23187 counteracted the actions of adrenomedullin. In patients with essential hypertension, who had higher order parameter values, the membrane fluidity of erythrocytes was significantly lower than in the normotensive control subjects (order parameter: 0.728 ± 0.004 in hypertensives,n= 20; 0.692 ± 0.002 in normotensives,n= 36,P< 0.01). The effect of adrenomedullin on membrane fluidity was more pronounced in the erythrocytes of essential hypertensive than in the erythrocytes of normotensive subjects (change in the order parameter with adrenomedullin at 10−9mol/l:−4.2 ± 0.3% in hypertensives,n= 20; −1.8 ± 0.2% in normotensives,n= 20,P< 0.05; adrenomedullin at 10−8mol/l: −4.5 ± 0.3% in hypertensives,n= 20; −1.8 ± 0.2% in normotensives,n= 36,P< 0.05).ConclusionsThe results of the present study demonstrate that adrenomedullin significantly increased the membrane fluidity of erythrocytes. The mechanisms were partially mediated by a prostaglandin E1- and cyclic AMP-dependent pathway which might be linked to changes in intracellular calcium kinetics. The greater effect of adrenomedullin in patients with essential hypertension suggests that the peptide might actively participate in the regulation of membrane functions in hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveWe compared diurnal patterns of blood pressure in Wistar–Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP), and analyzed the relationship between the change in diurnal patterns of blood pressure and target-organ damage in SHRSP.Materials and methodsBlood pressure, heart rate and motor activity in the three groups of rats were continuously monitored by radiotelemetry, from 1100 h on the first measuring day to 1300 h on the third measuring day. The left ventricular weight and the ratio of β-myosin heavy chain to α-myosin heavy chain in the cardiac left ventricle, morphological changes in the glomerular basement membrane in the kidney, 24 h urinary protein excretion and brain weights were also measured in 10-, 12-or 17-week-old SHRSP.ResultsThe SHR circadian blood pressure rhythm exhibited a pattern which peaked during the rats' active (light-off or dark) phase, but the peak time was a little closer to the resting (light-on) phase compared with that for WKY rats. Although the circadian blood pressure rhythm for 10-week-old SHRSP was similar to that observed for SHR, the patterns in 12-and 17-week-old SHRSP were shifted further towards the resting phase. Heart and left ventricular weight increased with the progression of hypertension. The ratio of β-to α-myosin heavy chain in the left ventricle was higher in 12-and 17-week-old SHRSP than in 10-week-old SHRSP. Brain weight was increased significantly in 17-week-old SHRSP compared with 10-and 12-week-old SHRSP. Increased urinary protein excretion and morphological changes in the glomerular basement membrane in the kidney were observed in 12-and 17-week-old SHRSP.ConclusionsThese data suggest that SHRSP have an abnormal circadian blood pressure rhythm associated with hypertensive target-organ damage. This rat strain may therefore be a useful model in which to investigate the mechanisms responsible for the alteration in the circadian blood pressure rhythm, and to analyze the relationship between the abnormal circadian rhythm and target-organ damage.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesTo evaluate the relative participation of endothelium-derived factors mediating relaxation in response to acetylcholine in isolated mesenteric vascular beds from rats treated chronically with NG-nitro-L-arginine methylester (L-NAME); and to compare the consequences of prolonged treatment with either an angiotensin converting enzyme inhibitor or a calcium channel blocker on the components of acetylcholine-induced relaxation in this vascular preparation.Materials and methodsMale Sprague-Dawley rats were treated for 8 weeks with L-NAME (40 mg/kg per day), quinapril (10 mg/kg per day), diltiazem (100 mg/kg per day), L-NAME + quinapril and L-NAME + diltiazem. Systolic blood pressure was estimated by a tail-cuff plethysmograph. Relaxing responses to acetylcholine (10−12to 10−8mol) in mesenteric vascular beds precontracted with phenylephrine (10−5mol/l) were studied in the presence and absence of L-NAME (10−5mol/l), L-NAME + indomethacin (10−5mol/l) or L-NAME + indomethacin + potassium chloride (6 × 10−5mol/l). The area under the dose-response curve was used to calculate the approximate participation of nitric oxide, prostaglandins or endothelium-derived hyperpolarizing factor in the acetylcholine-induced relaxation.ResultsChronic administration of L-NAME increased blood pressure levels and vascular responsiveness to phenylephrine. Treatments with either quinapril or diltiazem reduced blood pressure levels and attenuated the increased response to phenylephrine. Relaxing responses to acetylcholine were similar in all groups, independently of the treatment received. The calculated participation of endothelium-derived hyperpolarizing factor in the acetylcholine-induced relaxation was higher than that of nitric oxide and prostaglandins in all groups, but was higher in L-NAME-treated than in untreated rats. In contrast, the participation of both nitric oxide and prostaglandins was higher in control than in L-NAME-treated rats. Quinapril increased the participation of prostaglandins in L-NAME-treated rats. Diltiazem increased the participation of nitric oxide in L-NAME-treated rats.ConclusionsThe administration of L-NAME in Sprague-Dawley rats increased the production of endothelium-derived hyperpolarizing factor as a compensatory mechanism to maintain acetylcholine-induced relaxation. Antihypertensive therapy with either quinapril or diltiazem produced a selective redistribution of the endothelial factors mediating acetylcholine-induced relaxation.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveSodium depletion stimulates the reninangiotensin and sympathetic nervous systems, which may affect the role of each of these systems in the regulation of vascular tone. We investigated the influence of sodium depletion on the roles of the angiotensin II type 1 receptor and the α1- and α2-adrenergic receptors, and on nitric oxide generation, in the regulation of human forearm vascular tone.Subjects and methodsWe studied the effects of the angiotensin II type 1 receptor antagonist losartan (0.1–3 μg/kg per min), angiotensin II (0.01–10 ng/kg per min), the α1– and α2-adrenoceptor antagonists doxazosin (3–100 ng/kg per min) and yohimbine (0.5–4 μg/kg per min) and the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 7.5–60 μg/kg per min) on forearm blood flow in control subjects (n= 12) and sodium-depleted subjects (n= 11). Sodium depletion was achieved by 3 days of pretreatment with 40 mg furosemide twice a day and a sodium-restricted diet. Forearm blood flow was measured by venous occlusion plethysmography.ResultsSodium depletion resulted in activation of the renin–angiotensin and sympathetic nervous systems, as indicated by increased levels of plasma renin, aldosterone and heart rate (P< 0.05). Blood pressure remained unchanged. Losartan at the highest dose increased forearmbloodflowinthesodium-depletedgroupby42 ± 9%, but had no effect in controls (P< 0.05). Both doxazosin and yohimbine caused an increased vasodilatory effect in the sodium-depleted versus the control group (228 ± 42 versus 83 ± 13% and 192 ± 24 versus 95 ± 8%, respectively;P< 0.05). The constrictor effects by angiotensin II and L-NMMA of −65 ± 6% and −79 ± 4%, respectively, in controls were unchanged by sodium depletion.ConclusionsIn sodium-depleted subjects, endogenous angiotensin II appears to play a role in the regulation of forearm vascular tone, in contrast to sodium-replete conditions. Furthermore, in these subjects the role of α1- and α2-adrenoceptors in the regulation of forearm vascular tone was enhanced compared with control conditions. Neither the forearm vascular effects of exogenously infused angiotensin II nor those of baseline nitric oxide production were influenced by sodium depletion.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundIncremental elastic modulus, which is the slope of the relationship between stress and strain of arterial vessels, is a marker of wall material stiffness. The radial artery incremental elastic modulus, which is not influenced by age, is normal or reduced in patients with essential hypertension but increased in patients with end-stage renal disease. Authors of studies on hypertension largely ignore the question of whether the incremental elastic modulus, measured in the common carotid artery as typical of a central artery site, differs according to age or to the presence of end-stage renal disease or both.Subjects and methodsThe carotid incremental elastic modulus was measured in 208 hypertensive patients divided into four groups according to age (≤ or > 55 years) and the presence or absence of end-stage renal disease. The incremental elastic modulus was calculated from transcutaneous measurements of arterial internal diameter and wall thickness (echo-tracking device) and carotid pulse pressure (tonometry). Because the four groups of subjects had the same mean arterial pressure, the static incremental elastic modulus was calculated both in isobaric conditions and for the same wall stress.ResultsIn nonuremic subjects, lumen diameter, wall thickness and the incremental elastic modulus were significantly (P< 0.001) increased in older subjects whereas compliance and distensibility were decreased. The mean (± SD) elastic modulus was 0.41 ± 0.14 × 103kPa in younger and 0.71 ± 0.28 × 103kPa in older subjects. In uremic subjects, the corresponding values were 0.48 ± 0.30 and 0.90 ± 0.49 × 103kPa, and therefore higher than in nonuremic subjects, irrespective of age. Multiple regression analysis showed that age, mean arterial pressure and the presence of end-stage renal disease independently influenced carotid diameter, distensibility and the incremental elastic modulus.ConclusionsIn hypertensive patients, the carotid incremental elastic modulus is increased independently in aging men and women and in the presence of uremia. This increase is not dependent on mechanical factors such as the level of mean blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that hemodynamic measurements in patients with essential hypertension are related independently to plasma leptin levels.Patients and methodsWe measured plasma leptin, insulin, office and ambulatory blood pressure and heart rate in 60 men with untreated mild hypertension.ResultsPlasma leptin correlated significantly with body mass index (r= 0.43,P= 0.001), 24 h heart rate (r= 0.35,P= 0.006) and 24 h diastolic blood pressure (r= 0.27,P= 0.04) but not with age (r= 0.03;P= 0.85) or 24 h systolic blood pressure (r/−0.08,P= 0.56). Plasma leptin levels adjusted for body mass index correlated significantly with 24 h heart rate (r= 0.36,P= 0.005) but not with 24 h diastolic blood pressure (r= 0.19,P= 0.15). We divided the patient population into tertiles of body mass index-adjusted plasma leptin levels. Age, plasma insulin, blood pressure, smoking status and physical activity habits were similar across the adjusted leptin tertiles. Patients from the third tertile of adjusted plasma leptin distribution (those with leptin levels higher than would be expected on the basis of body mass index) had significantly faster ambulatory heart rates than subjects from both the first and the second tertiles. The difference in heart rate across the three tertiles was most pronounced for the night-time values.ConclusionsIn patients with essential hypertension, heart rate is faster in those patients with higher plasma leptin levels. This relationship is independent of age, body mass index, insulin levels, blood pressure level, smoking status and physical activity.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo test the hypothesis that insulin increases heart rate and arterial pressure via direct effects on the central nervous system.Methods and designInsulin was infused into the cerebral circulation of conscious dogs (n= 8) chronically instrumented for continuous infusions and measurement of arterial pressure, cardiac output, heart rate and other hemodynamic variables. In acute experiments, insulin was infused for 30 min into either a carotid or vertebral artery at several rates calculated to increase cerebral circulation insulin concentrations to levels in the physiological or pathophysiological range. It was infused with and without a simultaneous glucose infusion. During long-term experiments, insulin was infused into either a carotid or a vertebral artery for 4 days at 0.4 or 0.2 mU/kg per min, respectively.ResultsInsulin infusion alone into the cerebral circulation produced no changes in any measured cardiovascular variable. A simultaneous glucose infusion also produced no changes in cardiovascular dynamics, except at the highest rate of infusion into the carotid artery. The changes seen at the highest rate of infusion are unlikely to be insulin-induced, since similar changes occurred when either glucose or saline was infused in the absence of any insulin infusion. Long-term insulin infusion (4 days) into carotid or vertebral arteries also produced no changes in any measured cardiovascular or renal variable.ConclusionsThese results provide no evidence that insulin, at physiological or pathophysiological concentrations, increases heart rate or arterial pressure by acting directly on the central nervous system, and suggest that sympathetic activation and tachycardia previously observed with systemic hyperinsulinemia may be secondary to peripheral actions of insulin.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID