摘要:

ObjectivesTo evaluate whether the differential distribution of apolipoprotein E among lipoprotein fractions and hepatic expression of the apolipoprotein E gene are causal factors in the regulation of lipid metabolism and physiological functions in young and aged spontaneously hypertensive and stroke-prone rats.Design and methodsBiochemical analyses were performed on serum and hepatic specimens from young (2-month-old) and aged (8-month-old) spontaneously hypertensive rats, stroke-prone spontaneously hypertensive rats and normotensive Wistar–Kyoto rats. Levels of apolipoprotein E among various lipoprotein fractions were determined using sodium dodecyl sulfatepolyacrylamide gel electrophoresis. Liver concentrations of apolipoprotein E mRNA were analyzed by Northern blotting and relative levels of apolipoprotein E mRNA in different strains of rats were compared. Statistical analysis was performed by measuring correlations between hepatic apolipoprotein E mRNA levels and biological parameters.ResultsLevels of apolipoprotein E in high-density and low-density lipoproteins were significantly lower in hypertensive rats than in age-matched normotensive Wistar–Kyoto rats. Although there was a significant increase in high-density lipoprotein apolipoprotein E contents in all aged animals, the elevation in aged hypertensive rats was much less than that in aged normotensive rats. Levels of apolipoprotein E in the very-low-density lipoprotein fraction were diminished in young stroke-prone rats but were remarkably high in aged rats. Steady-state levels of apolipoprotein E mRNA increased with age in all strains of rats, whereas aged hypertensive rats exhibited lower apolipoprotein E mRNA levels than aged normotensive rats.ConclusionsThe distribution of apolipoprotein E among various lipoprotein fractions was dramatically altered with age, and the alteration varied among different strains of rats. The differential distribution of apolipoprotein E in young and aged spontaneously hypertensive and strokeprone rats suggests that apolipoprotein E could be a causal factor that disturbs the homeostasis of lipids and lipoproteins and perturbs physiological functions in hypertensive rats.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveWe have previously shown that atrial natriuretic peptide (ANP) modulates cardiac barosensitive afferent pathways to enhance reflex bradycardia in rats. The present study examined whether B-type natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) also modulate heart rate reflex function.DesignBaroreflex bradycardia was evoked by rapid (over 4–6 s) intravenous (i.v.) infusions of methoxamine (100 μg/kg; ‘ramp’ baroreflex technique) in the presence of infused i.v. natriuretic peptide and of vehicle (0.9% saline, 270 μl/h) in conscious adult Munich–Wistar rats. Initially a dose–response study to ANP (infused at 25, 50 and 100 pmol/kg per min i.v.) was performed in 10 rats to determine an appropriate dose for subsequent experiments with the other peptides. In a separate group of 11 animals, rat BNP-32 and rat CNP-22 were infused at 50 pmol/kg per min i.v.ResultsReflex responses to ANP were dose-related, with a significant increase in baroreflex sensitivity of 50 ± 15% at the 25 pmol dose, 102 ± 10% at the 50 pmol dose and 117 ± 11% at 100 pmol dose (allP< 0.05). BNP and CNP (50 pmol/kg/min i.v.) substantially increased baroreflex bradycardia (by 115 ± 17% and 62 ± 15%, respectively;P< 0.05) compared to vehicle infusion.ConclusionsBoth BNP and CNP augmented baroreflex slowing of heart rate in response to rapid increases in blood pressure in rats. Whereas other reports have shown marked differences in cardiovascular responses between the natriuretic peptides, particularly with CNP, our findings demonstrate an important common action of ANP, BNP and CNP to facilitate vagal heart rate baroreflexes.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveCardiotrophin-1 is a cytokine, a novel member of the interleukin-6 superfamily, which is isolated from mouse embryoid bodies. It is known to bind a gp130/leukemia inhibitory factor (LIF) receptor heterodimer and to induce myocyte hypertrophy. Accumulating evidence indicates that a gp130 signaling pathway is involved in cardiac development and ventricular hypertrophy.MethodsIn order to elucidate the pathophysiologic significance of cardiotrophin-1 in ventricular hypertrophy associated with hypertension, we examined the level of cardiotrophin-1 mRNA in the ventricle of spontaneously hypertensive rats/Izm stroke-prone (SHRSP/Izm) in neonates, and at 4-, 12- and 20-weeks of age by Northern blot analysis. We also examined the gene expression of LIF by Northern blot and reverse transcription-polymerase chain reaction analyses.ResultsNo significant difference was observed in the level of cardiotrophin-1 mRNA in the ventricle between SHRSP/Izm and Wistar–Kyoto/Izm (WKY/Izm) neonates. However, the level of cardiotrophin-1 mRNA in the ventricle was significantly augmented in 4-week-old SHRSP/Izm, which did not yet show overt ventricular hypertrophy, and its augmented expression lasted for the duration of the experimental period. The difference in the level of cardiotrophin-1 mRNA between the two strains was most prominent at the age of 4 weeks. This augmented expression of the cardiotrophin-1 gene was not related to the severity of left ventricular hypertrophy. The level of cardiotrophin-1 mRNA in other organs, including the kidney and lung, showed no significant change with aging and was not different between the two strains. After longterm treatment with lisinopril, levels of cardiotrophin-1 mRNA were not changed, although it morphologically prevented the development of left ventricular hypertrophy. LIF mRNA was not detected in any ventricles examined by Northern blot analysis.ConclusionsThe present study demonstrates that the expression of cardiotrophin-1 mRNA is increased in the early stage of ventricular hypertrophy in SHRSP/Izm and it remains elevated after hypertrophy has been established. However, it is unlikely that cardiotrophin-1 plays a mechanistic role in the development and maintenance of left ventricular hypertrophy in SHRSP/Izm. The present study also suggests that cardiotrophin-1, but not LIF, is a possible candidate for natural ligand of a gp130 signaling pathway in the heart.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine whether the decision to treat uncomplicated mild hypertension with drugs, in accordance with the World Health Organization International Society of Hypertension (WHO/ISH) guidelines based on a series of blood pressure (BP) measurements over 6 months, resulted in the treatment of patients at high risk on the basis of echocardiography.MethodsOne hundred and eighteen patients with mild hypertension (diastolic blood pressure 90–105 mmHg and/or systolic blood pressure 140–180 mmHg) were examined by echocardiography at inclusion and followed up for 6 months by a single physician unaware of the echographic results.ResultsDrug treatment was given to 48 patients, and 70 remained untreated. Treated patients had higher echographic indices than untreated patients (allP< 0.05): left ventricular (LV) mass/body surface area (83.0 ± 15.6 versus 75.3 ± 14.8 g/m2), inter-ventricular septal thickness (9.7 ± 1.7 versus 8.5 ± 1.3 mm), LV posterior wall thickness (8.4 ± 1.1 versus 7.8 ± 1.1 mm), relative wall thickness (0.37 ± 0.06 versus 0.34 ± 0.06). LV geometry was normal in 98 patients, and 20 had LV concentric remodelling. The 10-year coronary disease risk (Framingham equation) was higher in the 20 patients with concentric remodelling than in those with normal LV geometry (10.4 versus 4.2%;P< 0.005). Nine of these 20 patients were still untreated at the end of the 6-month follow-up period.ConclusionRigorous application of the WHO/ISH clinical guidelines in a group of mild hypertensive patients led to the treatment of patients with slightly higher LV mass and more concentric LV geometry than were found in those not treated. However, a high-risk subgroup, with concentric remodelling, was not identified and left untreated.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundAngiotensin II has been found to be a growth stimulating factor for myocardial cells. In humans, angiotensin II infusion causes vasoconstriction in systemic and renal vasculature and leads to aldosterone secretion. Our hypothesis was that hyper-responsiveness to angiotensin II is related to left ventricular mass in human essential hypertension.Methods and resultsIn 30 normotensive individuals and 30 subjects with mild essential hypertension (white men, mean age 26 ± 3 years), the responsiveness to angiotensin II was assessed by measuring changes in mean arterial pressure, renal blood flow, glomerular filtration rate and aldosterone secretion in response to i.v. angiotensin II infusion (0.5 and 3.0 ng/kg per min). The provoked changes to angiotensin II infusion were similar in the normotensive and hypertensive group with the exception of an exaggerated increase in mean arterial pressure in hypertensives (14 ± 5 versus 10 ± 5 mmHg,P< 0.001 at 3.0 ng/kg per min angiotensin II). The increase in mean arterial pressure was correlated with left ventricular mass in hypertensive subjects (angiotensin II 0.5 ng/kg per min:r= 0.49,P< 0.005; angiotensin II 3.0 ng/kg per min:r= 0.35,P< 0.05); no such correlation was found in the normotensive group. After taking into account baseline mean arterial pressure and body mass index, the increase in mean arterial pressure to angiotensin II 0.5 ng/kg per min was still correlated with left ventricular mass (partialr= 0.50,P< 0.01). Similarly, the change of glomerular filtration rate but not of renal blood flow in response to angiotensin II 0.5 ng/kg per min was correlated with left ventricular mass, (r= 0.42,P< 0.02) in the hypertensive group but not in the normotensive one. This relationship remained significant even after taking baseline glomerular filtration rate, mean arterial pressure and body mass index into account (partialr= 0.43,P< 0.05).ConclusionHyper-responsiveness to angiotensin II is related to an increased left ventricular mass in hypertensive subjects independent of blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesFirst, to evaluate the prevalence of clinic blood pressure (BP) control (BP ≤ 140/90 mmHg) in a representative sample of treated hypertensive patients followed in our hypertension clinic. Second, to assess in a subgroup of these patients: (a) the proportion of BP control with both clinic blood pressure (CBP ≤ 140/90 mmHg) and daytime ambulatory blood pressure (ABP) (≤ 132/85 mmHg) criteria, and (b) the prevalence of echocardiographic left ventricular hypertrophy (LVH) (left ventricular mass index, LVMI > 125 g/m2in men and > 110 g/m2in women).Design and methodsSeven hundred consecutive hypertensive patients who attended our hypertension centre clinic during a period of 6 months and who had regularly been followed up by the same medical team were included in the study. BP was taken in the clinic by a doctor using a mercury sphygmomanometer with the participants seated. Seventy-four patients with similar demographic and clinical characteristics to the entire population of participants underwent complete echocardiographic examination and 24 h ABP monitoring.ResultsDuring follow-up, 352 of the treated patients had clinic BP ≤ 140/90 mmHg, 198 ≤ 160/95 mmHg and 150 > 160/95 mmHg, indicating that BP control was satisfactory in 50.3%, borderline in 28.3% and unsatisfactory in 21.4% of the cases. In the subgroup of 74 patients, the proportion of individuals with satisfactory clinic BP control (CBP ≤ 140/90 mmHg) was higher (50.0 versus 33.6%) than with satisfactory ABP control (daytime ABP values ≤ 132/85 mmHg). LVH was found in 21 of the 74 patients (28.3%): 12 of them had unsatisfactory CBP control and 19 had unsatisfactory ABP control. LVMI did not correlate with CBP values but only with ABP values (mean 24 h systolicr= 0.47, diastolicr= 0.40,P< 0.001; mean daytime systolicr= 0.45, mean daytime diastolicr= 0.39,P< 0.001; mean night-time systolicr= 0.38, mean night-time diastolicr= 0.38,P< 0.001).ConclusionThis study demonstrates that hypertensive patients managed in a hypertension centre clinic have satisfactory CBP control in 50% of cases, but this rate seems to over-estimate the effective BP control during daily life. A large fraction of patients show persistence of LVH and this evidence of organ damage almost entirely concerns individuals with poor ABP control.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo assess whether chronic long-term calcium antagonist therapy may increase genotoxicity, the chromosome aberration test, a widely accepted genotoxic assay, was usedex vivoin peripheral human lymphocytes of patients with or without long-term exposure to calcium antagonist therapy.Methods and resultsIn a case–control study design, we evaluated 30 ischaemic and/or hypertensive patients (22 males, eight females; age 59.4 ± 1.5 years), under chronic calcium antagonist treatment (group I), for more than 3 years (4.4 ± 0.34 years) and 30 age-matched subjects, without any previous exposure to calcium antagonists (group II). Venous blood samples were collected from the patients and cultures were set up for cytogenetic analysis by standard methods.For each subject, 100 metaphases were scored. The two groups showed similar values (mean ± SEM) for percentage aberrant cells (group I 2.6 ± 0.3 versus group II 2.5 ± 0.3, not significant), percentage structural aberrations (group I 1.9 ± 0.3 versus group II 1.8 ± 0.2, not significant) and percentage numerical aberrations (group I 0.70 ± 0.2 versus group II 0.73 ± 0.2, not significant).ConclusionsLong-term calcium antagonist therapy is not associated with an increased incidence of chromosomal indices of genotoxic damage in humans.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID