摘要:

ObjectiveExtracellular matrix, particularly type I fibrillar collagen, provides tensile strength that allows cardiac muscle to perform systolic and diastolic functions. Collagen is induced during the transition from compensatory hypertrophy to heart failure. We hypothesized that cardiac stiffness during decompensatory hypertrophy is partly due to a decreased elastin: collagen ratio.Materials and methodsWe prepared left ventricular tissue homogenates from spontaneously hypertensive rats (SHR) aged 30–36 weeks, which had compensatory hypertrophy with no heart failure, and from SHR aged 70–92 weeks, which had decompensatory hypertrophy with heart failure. Age- and sex-matched Wistar–Kyoto (WKY) rats were used as normotensive controls. In both SHR groups, increased levels of collagen were detected by immuno-blot analysis using type I collagen antibody. Elastin and collagen were quantitated by measuring desmosine/isodesmosine and hydroxyproline spectrophometrically, respectively. To determine whether the decrease in elastin content was due to increased elastinolytic activity of matrix metalloproteinase-2, we performed gelatin and elastin zymography on left ventricular tissue homogenates from control rats, SHR with compensatory hypertrophy and SHR with heart failure.ResultsThe elastin: collagen ratio was 0.242 ± 0.008 in hearts from WKY rats. In SHR without heart failure, the ratio was decreased to 0.073 ± 0.003 and in decompensatory hypertrophy with heart failure, the ratio decreased to 0.012 ± 0.005. Matrix metalloproteinase-2 activity was increased significantly in SHR with heart failure compared with controls (P< 0.001). The level of tissue inhibitor of metalloproteinase-4 was increased in compensatory hypertrophy and markedly reduced in heart failure. Decorin was strongly reduced in decompensatory heart failure compared with control hearts.ConclusionsSince collagen was induced in SHR with heart failure, decorin and elastin were decreased and the ratios of gelatinase A and elastase to tissue inhibitor of metalloproteinase-4 were increased, we conclude that heart failure is associated with adverse extracellular matrix remodeling.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo investigate the feasibility of using intravascular ultrasound to characterize normal and diseased renal arteries.Materials and methodsForty-four renal artery specimens from 21 humans, removed at autopsy, were studied with intravascular ultrasoundin vitro. From each vascular specimen, two to four sets of corresponding intravascular ultrasound images and histologic sections were subjected to qualitative analysis. The renal arterial wall was considered normal by intravascular ultrasound when the wall thickness (intima and media) was 0.5 mm or less. On intravascular ultrasound imaging, a distinction was made between bright lesions with or without peripheral shadowing (i.e. calcification). Histological sections were examined and fibromuscular lesions were scored with or without calcifications. Quantitative analysis of a multitude of intravascular ultrasound cross-sections (interval 5 mm) included assessment of the lumen area, vessel area, plaque area and percentage area obstructed. The target site (smallest lumen area) was compared with a reference site (largest lumen area before the first major side branch).ResultsOf the 130 corresponding intravascular ultrasound images and histologic sections analysed, 55 were normal and 75 presented a bright lesion on ultrasound; in 31 lesions, peripheral shadowing was involved. The sensitivity of the intravascular ultrasound in detecting calcifications was 87%, and the specificity was 89%. Lumen area reduction at the target site was associated with vessel and plaque area enlargement in eight specimens, with plaque area enlargement in 12 specimens and with a vessel area reduction in 21 specimens.ConclusionsIntravascular ultrasound is a reliable technique for distinguishing renal arteries with or without a lesion. Both plaque development and local vessel narrowing may result in renal artery stenosis.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo characterize glomerular and preglomerular vascular angiotensin II receptors during the acute phase of nonrenin-dependent one-kidney, one clip hypertension in rats, using the angiotensin II antagonists losartan and PD 123319, and to investigate their regulation after renin–angiotensin system blockade with either an angiotensin converting enzyme inhibitor, captopril, or an angiotensin II receptor antagonist, TCV-116.Materials and methodsOne-kidney, one clip hypertension was produced in male Sprague-Dawley rats by placing a silver clip (internal diameter 0.2 mm) on the left renal artery and removing the contralateral kidney. After 1, 2 or 4 weeks, the rats were killed, and their glomerular and preglomerular vascular membranes were purified. Competitive binding studies were performed using specific angiotensin II antagonists. Similarly, one-kidney, one clip hypertension was allowed to develop for 2 weeks before treatment with captopril or TCV-116 for 2 weeks.ResultsCompetitive binding studies showed that only the angiotensin II type 1 (AT1) receptor was detected on both glomeruli and preglomerular vessels of all groups. The vascular AT1 receptor density was significantly higher in the 1 and 2 week one-kidney, one clip groups, but the glomerular receptor density was not different in these rats compared with age-matched uninephrectomized controls. The glomerular receptor density was significantly higher in captopril-treated rats and significantly lower in TCV-116–treated rats compared with untreated and control rats, but no significant changes were detected in any groups in vascular AT1 receptor density.ConclusionsAngiotensin II receptors on preglomerular vessels and glomeruli are differentially regulated during the early phase of hypertension and after renin-angiotensin system blockade. Vascular angiotensin II receptors are upregulated in the early phase of hypertension whereas glomerular angiotensin II receptors are not. However, after renin-angiotensin system blockade, glomerular but not vascular angiotensin II receptors were differentially regulated according to the type of blockade.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveChronic inhibition of nitric oxide synthesis has been shown to cause arterial hypertension and an important blunting of the pressure diuresis and natriuresis response. The mechanisms mediating these abnormalities are not completely established. We therefore studied the effects of endothelin on these alterations.Materials and methodsPressure diuretic and natriuretic relationships were evaluated in rats treated chronically (3 weeks) with the nitric oxide synthesis inhibitor Nω-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg per day), alone or in combination with bosentan sodium salt (acute treatment: 10 mg/kg, intravenously; chronic treatment: 10 mg/kg per day).ResultsChronic treatment with L-NAME significantly elevated mean arterial pressure (143.7 ± 2.8 mmHg versus 102.8 ± 1.6 in controls), reduced the glomerular filtration rate and renal blood flow and shifted the pressure diuretic and natriuretic responses to the right. Treatment with bosentan, either acute or chronically, did not attenuate the arterial hypertension of the L-NAME-treated rats but normalized the glomerular filtration rate and renal blood flow. In spite of the normalization of renal hemodynamics, the pressure diuretic and natriuretic responses of the bosentan-treated groups were not normalized, although chronic bosentan significantly improved the pressure natriuretic response.ConclusionsThese results indicate that endothelin participates in the renal hemodynamic and excretory alterations that follow chronic inhibition of nitric oxide synthesis. However, the arterial hypertension is not mediated by endothelin activation.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo assess the antihypertensive efficacy and safety of the novel AT1receptor antagonist, telmisartan, compared with that of enalapril in elderly patients with mild to moderate hypertension.DesignA 26–week, multicenter, double-blind, parallel-group, dosage titration study.MethodsA total of 278 patients aged ≥ 65 years were randomized to either telmisartan or enalapril once a day. The telmisartan dosage was increased from 20 to 40–80 mg and that of enalapril from 5 to 10–20 mg at 4–week intervals until trough supine diastolic blood pressure was < 90 mmHg. After 12 weeks, hydrochlorothiazide at 12.5–25 mg once a day was added to the treatment regimen of those patients not controlled on monotherapy.ResultsBoth treatments lowered blood pressure in a comparable and clinically meaningful manner. The adjusted mean changes from baseline in supine diastolic blood pressure at trough were −12.8 mmHg for telmisartan and −11.4 mmHg for enalapril (P= 0.074). Mean changes in supine systolic blood pressure were −22.1 mmHg for telmisartan and −20.1 mmHg for enalapril (P= 0.350). Overall, 63 and 62% of patients responded to telmisartan and enalapril, respectively, with a supine diastolic blood pressure of < 90 mmHg. Both regimens provided effective blood pressure lowering over the 24 h dosing interval, as determined by ambulatory blood pressure monitoring. Both regimens were well tolerated; however, patients on the enalapril regimen had more than double the incidence of treatment-related cough compared with those on the telmisartan regimen (16 versus 6.5%).ConclusionsThese results demonstrate that telmisartan is well tolerated and is at least as effective as enalapril in treating elderly patients with mild to moderate hypertension.

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