摘要:

BackgroundHypertensive cardiomyopathy is a major risk factor for the development of chronic heart failure.ObjectiveTo investigate whether treatment with an angiotensin converting enzyme inhibitor (ACEI) or with an angiotensin type 1 receptor antagonist (AT1-RA) is sufficient to prevent the development of hypertensive cardiomyopathy and cardiac contractile dysfunction. Special emphasis was placed on the effects of both treatments on sarcoplasmic reticulum Ca2+-ATPase (SERCA 2a) gene expression as a major cause of impaired diastolic cardiac relaxation.Methods and resultsEight-week-old rats harboring the mouse renin 2dgene [TG(mREN2)27] were treated for 8 weeks with 100 mg/kg captopril (Cap) in their food and 100 mg/kg of the AT1-RA Bay 10-6734 (Bay) in their food. Untreated TG(mREN2)27 and Sprague–Dawley rats (SDR) were used as controls. Both treatment regimens normalized the left ventricular weight, which was increased significantly (P< 0.001) in TG(mREN2)27. Both treatments normalized the left ventricular endsystolic and end-diastolic pressures, which were significantly (P< 0.001) higher in TG(mREN2)27 than they were in SDR, and they improved the velocity of the decrease in pressure [P< 0.05, Bay and Cap versus TG(mREN2)27]. Decreased left ventricular SERCA 2a mRNA and protein levels and increased atrial natriuretic peptide messenger RNA levels were normalized by Bay and Cap treatments (P< 0.05, Bay and Cap versus TG(mREN2)27, by Northern and Western blotting). According to radioimmunoassay and an enzyme assay, respectively, Bay, but not Cap, increased plasma angiotensin I concentrations and the renin activity above normal levels (P< 0.05), whereas myocardial angiotensin II concentrations (determined by radioimmunoassay), which were significantly (P< 0.05) increased in TG(mREN2)27, were normalized equally by Bay and Cap.ConclusionsIn renin-induced hypertensive cardiomyopathy, left ventricular diastolic dysfunction occurs at the stage of compensated myocardial hypertrophy. The decreased left ventricular relaxation velocity might be due to reduced SERCA 2a gene expression. In this model of hypertensive cardiomyopathy, AT1-RA and ACEI treatments are similarly effective at reducing the arterial pressure, preventing myocardial hypertrophy and diastolic contractile dysfunction. Normalization of SERCA 2a gene expression, either by AT1-RA or by ACEI treatment, might contribute to the improvement in diastolic function.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectivesTo study left ventricular longitudinal shortening in arterial hypertension and the relative contribution of longitudinal and circumferential fiber shortening to ventricular ejection.MethodsTwo-dimensional and M-mode echocardiograms were obtained for 50 normotensive subjects (aged 49 ± 12 years) and 50 never-treated mild hypertensive patients (aged 49 ± 11 years), to measure the minor-axis endocardial and midwall shortening, long-axis shortening and ejection fraction.ResultsThe midwall shortening was lower in hypertensive than it was in normotensive subjects (P< 0.001) and was related inversely to the circumferential wall stress for both groups (P< 0.04 and 0.0001, respectively). The long-axis shortening in hypertensive patients (22.2 ± 4.2%) and in normotensives (23.6 ± 5.4%) was not statistically different, and was not related either to the meridional or to the circumferential wall stress. The ejection fraction was also similar for the two groups (68.2 ± 6.3 versus 68.6 ± 5.6%). Both for normotensive and for hypertensive subjects, the ejection fraction was influenced mainly by the midwall shortening (61 and 40% of the variance for normal and hypertensive individuals, respectively), with a minor contribution from the long-axis shortening, which was 7% for normotensive subjects and 18% for hypertensive patients, a statistically significant difference (P< 0.001). The combined effect of midwall and longitudinal shortenings on the ejection fraction was regulated by the relative wall thickness, and was maximal for hypertensive patients with an ejection fraction greater than that predicted by the midwall shorteningConclusionsLeft ventricular ejection is produced principally by circumferential shortening and is related independently to the relative wall thickness. In the presence of arterial hypertension and an altered cardiac load, longitudinal shortening becomes an important mechanism by which to augment ejection, thereby offsetting the reduction in midwall shortening.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundCardiac angiotensin AT1receptors have been found in several animal species. In-vitro studies performed on cardiac preparations have shown that angiotensin II (ANG II) exerts a positive inotropic effect; however, in-vivo results have allowed no definitive conclusion to be drawn. The reasons behind these controversial results remain unknown, and could originate both from different experimental conditions and from the techniques used to assess myocardial contractility.ObjectiveTo investigate, by means of echocardiographic measurements, whether ANG II, administered to intact and to sinoaortic denervated isoflurane-anesthetized rabbits, was able to directly increase myocardial contractility.MethodsThe effect of ANG II on cardiac contractility was assessed with the use of simultaneous pressure measurements and Doppler-echocardiographic recordings. Specifically, we used both the relationship between the left ventricular end-systolic wall stress and the velocity of heart-rate-corrected circumferential fiber shortening (VCFC) and the maximum rate of rise of the ventricular pressure as indices of changes in myocardial contractility. Cardiac contractility was evaluated both in intact and in chronically sinoaortic denervated isoflurane-anesthetized rabbits under basal conditions and after ANG II infusion (50 ng/kg per min).ResultsAfter ANG II infusion, increases in mean arterial blood pressure, left ventricular end-diastolic diameter and pressure were observed both in intact and in chronically sinoaortic denervated rabbits. The left ventricular end-systolic wall stress (a function of the mean arterial pressure and chamber size) and the maximum rate of rise of the ventricular pressure rose markedly in rabbits of both groups, whereas the VCFC decreased significantly. However, when we compared the VCFC under ANG II infusion with that calculated at the same level of left ventricular afterload under basal conditions, we observed that ANG II infusion induced no significant change in VCFC either in intact or in chronically sinoaortic denervated rabbits.ConclusionOur results indicate that administration of ANG II to isoflurane-anesthetized rabbits induces a marked rise in ventricular pre- and after-loads and exerts no significant effect on the cardiac contractility. In light of this, it is reasonable to assume that the short-term increase in arterial blood pressure can be ascribed mainly to the increase in peripheral arterial resistance.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo investigate the roles of the reninangiotensin system and blood pressure in cardiac hypertrophy caused by a pressure overload.MethodsCardiac hypertrophy was induced by constricting the abdominal aorta above the renal arteries. After they had been banded, the rats were treated with the lower (1 mg/kg per day) or the higher (10 mg/kg per day) dose of quinapril [an angiotensin converting enzyme (ACE) inhibitor], or the lower (1 mg/kg per day) or the higher (10 mg/kg per day) dose of TCV-116 [an angiotensin II (AngII) AT1 receptor antagonist], for 4 weeks. Then, we measured the mean blood pressure (MBP), body weight, left ventricular weight (LVW), and serum and cardiac ACE activities.ResultsThe higher dose of quinapril and that of TCV-116 prevented left ventricular hypertrophy and MBP elevation. Both the higher and the lower doses of quinapril reduced the serum and cardiac ACE activities significantly, whereas the higher dose of TCV-116 reduced the cardiac ACE activity and increased the serum ACE activity. The lower dose of quinapril, however, exerted no significant effect on MBP and the LVW: body weight ratio, although it reduced the cardiac and serum ACE activities significantly. There was a significant positive correlation between the MBP and the LVW: body weight ratio regardless of the cardiac ACE activity in data from all groups (r = 0.676,P< 0.0001).ConclusionsOur data indicate the importance of the blood pressure as a determinant of cardiac hypertrophy because inhibition of cardiac ACE activity alone without lowering of the blood pressure is insufficient to prevent cardiac hypertrophy. Our results suggest the presence of other pathways for AngII production not mediated by ACE, or growth factors other than AngII in pressure-overload cardiac hypertrophy.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo describe various estimates of the quality of life (QOL) prior to and for 2 years after coronary artery bypass grafting (CABG) for patients with a history of hypertension compared with nonhypertensives.MethodsPatients in western Sweden in whom CABG had been performed between 1988 and 1991 participated. Their QOL was estimated from the Physical Activity Score, the Nottingham Health Profile, and the Psychological General Well-being Index.ResultsAll three questionnaires detected a significant improvement in QOL already at 3 months, which persisted at 1 and 2 years both for hypertensive and for nonhypertensive patients. With the Physical Activity Score and the Psychological General Well-being Index the improvement in QOL of hypertensive patients was less marked 3 months after the operation compared with that of nonhypertensives (P< 0.05). Two years after the CABG improvement was less marked for hypertensive patients than it was for nonhypertensive patients in terms of the Physical Activity Score (P< 0.01). With the Nottingham Health Profile the improvement was similar for hypertensive and nonhypertensive patients at each evaluation after the operation. With all three measures the results indicated that hypertensive patients had a worse QOL than did nonhypertensive patients. However, in a multivariate analysis considering other risk indicators simultaneously, a history of hypertension did not appear as an independent risk indicator for an adverse QOL 2 years after CABG.ConclusionThere was a significant improvement in various QOL estimates after CABG both for hypertensive and for nonhypertensive patients. The degree of improvement tended to be less marked for hypertensive patients than it was for nonhypertensive patients, especially 3 months after the operation and concerning physical activities. Hypertensives had a worse QOL than did nonhypertensives. However, the differences were small and could mainly be explained in terms of factors other than hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundHypertension features an exaggerated natriuresis after acute volume expansion. In humans, the degree of exaggerated natriuresis appears to be correlated inversely to the level of angiotensin (Ang) II.ObjectiveTo test the hypothesis that the degree of exaggerated natruresis is correlated to the level of Ang II by studying two rat models, transgenic rats (TGR) with an extra renin gene (TGR mRen2)27 and desoxycorticosterone acetate (DOCA)–salt rats, in comparison with Sprague–Dawley Hannover (SDH) rat controls.MethodsAll of the rats were uninephrectomized for 1 month. DOCA–salt rats were implanted with a DOCA pellet and drank 1% saline. Rats were anesthetized and their left kidneys were instrumented with renal sympathetic nerve activity (RSNA) electrodes and laser-Doppler cortical and medullary flow probes. The glomerular filtration rate, diuresis, and natriuresis were measured for 120 min after sodium loading (5% body weight 0.9% saline administered during 3 min). Kidneys were examined histologically.ResultsThe blood pressure in TGR and DOCA–salt rats was 40–50 mmHg higher than that in SDH rats, and decreased briefly after volume expansion for all groups. The diuresis and natriuresis of TGR and DOCA–salt rats were greater than those of SDH rats. The medullary blood flow increased and the cortical blood flow in SDH decreased, whereas the cortical blood flow in TGR and DOCA–salt rats remained high. The RSNA in rats of all groups decreased; however, this decrease was greater in SDH than it was in TGR and DOCA–salt rats. The histology was affected most severely for the DOCA–salt rats.ConclusionsExaggerated natriuresis occurred in hypertensive rats regardless of their Ang II status. Both strains were characterized by a smaller decrease in RSNA and a preserved cortical blood flow in the face of volume expansion. These data do not support the notion that exaggerated natriuresis is a function of renin-level suppression for rats.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID