摘要:

ObjectiveInvestigation of the effect of hypertension on endothelium-dependent relaxation and release of nitric oxide (NO) in normotensive and renal hypertensive rats.Design and methodsSprague-Dawley rats were randomly allocated into two groups: uninephrectomized controls and one-kidney one-clip (Goldblatt hypertension) hypertensive rats, a non-renin dependent model of hypertension. After 10 weeks and in the presence of the cyclooxygenase inhibitor indomethacin, simultaneous measurements of the NO concentration, measured with a NO-specific microelectrode and endothelium-dependent relaxation were performed in isolated rat superior mesenteric arteries.ResultsAddition of the NO scavenger, oxyhaemoglobin, showed that basal NO concentration was unaltered in arterial segments from hypertensive rats. In norepinephrine-contracted arteries, acetylcholine increased the NO concentration and caused relaxations, and both parameters were significantly reduced in renal hypertensive arteries. Relaxations induced by the NO donor,S-nitroso-N-acetylpenicillamine were reduced. The superoxide scavenger, superoxide dismutase, and the NO synthase substrate, l-arginine, did not change the increase in NO concentration or acetylcholine relaxation in arteries from normotensive or renal hypertensive animals. In contrast, the NO synthase inhibitor, asymmetric dimethyl l-arginine, reduced the NO concentration and acetylcholine relaxation, while these responses were abolished in the presence of oxyhaemoglobin.ConclusionsThis study provides direct evidence that reduced endothelium-dependent relaxations in the superior mesenteric artery from renal hypertensive rats is due, at least in part, to diminished NO release. The reduced NO release and relaxation persist in the presence of excess of substrate for NO synthase.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectivesMechanisms involved in hypertension in homozygous mice for the defective endothelial nitric oxide synthase gene (eNOS−/−) have not been fully elucidated. As NO is a potent vasodilator agent and possibly promotes angiogenesis, we investigated whether vasoconstriction and/or microvascular rarefaction could explain hypertension in these mice.MethodsImmunohistochemistry with mouse monoclonal smooth muscle α-actin antibody was used to detect arterioles, and quantification of arteriolar density was performed in the left ventricle and in the gracilis muscle of 12-week-old male eNOS+/+and eNOS−/−mice. Haemodynamic parameters – mean arterial pressure (MAP), cardiac index (CI), total peripheral résistance (TPR), myocardial blood flow, muscular blood flow and corresponding resistances – were measured or calculated using the fluorescent microsphere method in basal conditions and after infusion of sodium nitroprusside (SNP) (5 to 150 μg/kg per min) in eNOS−/−mice, compared with eNOS+/+mice.ResultsWe evidenced a significant decrease in arteriolar density in the heart (−16%,P<0.02) and in the gracilis muscle (−22%,P<0.05) in eNOS−/−mice. In basal conditions, eNOS−/−mice developed significant hypertension (MAP = 127±14 versus 77±14 mmHg,P<0.001) associated with decreased CI (−29%,P<0.001) and increased TPR (+ 125%,P<0.001). Coronary and gracilis muscular resistances were increased (by 75 and 89% respectively,P<0.001) compared with eNOS+/+mice, whereas myocardial and skeletal muscle tissue blood flows were not affected. After SNP administration (10 μg/kg per min), a dose that did not significantly modify haemodynamic parameters in eNOS+/+mice, MAP, TPR and regional resistances were normalized in eNOS−/−mice, showing that vasodilation may correct hypertension in eNOS−/−mice. However, under maximal vasodilating conditions, TPR and regional resistances remained significantly higher in eNOS−/−mice than those of eNOS+/+mice.ConclusionAnatomical and functional results show that both vasoconstriction and arteriolar rarefaction are involved in hypertension of eNOS−/−mice. Indeed, under maximal vasodilation, arterial pressure and TPR remained significantly higher in eNOS−/−mice than in eNOS+/+mice, evidencing a major role of microvascular rarefaction in this model of hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveUltrasonic tissue characterization of epi-aortic vessels may be useful to define the composition of atherosclerotic plaques. Videodensitometry provides a histogram representing the frequency distribution of gray levels corresponding to different compositions of the carotid wall. However, lack of standardization limits the clinical application of this technique. In the present study, the echoreflectivity (ER) pattern of atherosclerotic plaquesin vivowas compared with their histological pattern after surgical removal, and the reproducibility of measurement was tested.Design and methodsWe studied 19 hypertensive patients with a carotid artery stenosis⩾70%, eligible for carotid thromboendarterectomy (TEA). Before TEA, all patients underwent standard high-resolution B-mode carotid ultrasound. ER parameters (mean gray level, broad band, skewness, and kurtosis) were obtained in a region of interest selected along the whole plaque, between the intima–blood and the media–adventitia interfaces. The plaques removed during TEA were examined by a histologist and classified into three groups on the basis of fibrous tissue (FT) content: lipidic (FT<20%), fibrolipidic (20⩽FT⩽50%), and fibrous (FT>50%). Discriminant function analysis was used to evaluate classification efficacy of different histological groups based on ER parameters.ResultsHistologically, five lesions were classified as lipidic, six as fibrolipidic and eight as fibrous. Analysis of variance showed significant between group differences in all ER parameters. The combined use of all ER parameters provided correct classification of plaques in 94.73% of cases (P<0.0001), improving the classification made using single parameters. Intra-observer and inter-observer variabilities (Bland–Altman method) of mean gray level measurements were small.ConclusionsVideodensitometry can discriminate between tissue composition of carotid lesions and complement the quantitative assessment of intima–media thickness by additionally providing a well-reproducible semiquantitative evaluation of vascular wall constituents.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Objectives and designIsolated systolic hypertension (ISH) is the predominant form of hypertension in the elderly population and drug treatment is unsatisfactory. We compared the efficacy of an endothelin-receptor antagonist (darusentan), an angiotensin-receptor blocker (irbesartan) and a thiazide diuretic (hydrochlorothiazide, HCTZ) to prevent and regress pulse pressure (PP) elevation and remodeling of large and small arteries, in a rat model of ISH obtained by the chronic administration of warfarin and vitamin K1(WK).Methods and resultsWarfarin and vitamin K1treatment for 4 or 8 weeks led to an elevation of PP, associated with increases in aortic calcium deposition and the ratio of collagen to elastin (C/E). Despite these changes in the composition of the aortic wall, the global structure of the aorta was unchanged. In contrast, an outward hypertrophic remodeling was observed in the middle cerebral artery. An early treatment with all drugs (darusentan, irbesartan, HCTZ) prevented PP elevation, changes of aortic media composition and the development of vascular remodeling. However, after 4 weeks of ISH, only darusentan and irbesartan reduced PP when administered from week 4 to 8. Darusentan was the most effective to regress existent aortic calcification, while only irbesartan reversed small artery hypertrophic remodeling.ConclusionsDuring the development of ISH, drug treatment appears more beneficial when started early. Indeed, the three agents prevented PP elevation, aortic calcification and C/E increase in the aorta, and hypertrophy in small arteries. In contrast, once the disease is established, endothelin appears crucial in the maintenance of aortic calcification, while angiotensin II sustains small artery hypertrophy.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveA recent study demonstrated that free radicals were involved in the maintenance of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). Advanced glycation end-products (AGEs) accumulate progressively in the vasculature with ageing, and have been identified to be relevant mediators for various vascular complications. To elucidate the role of AGEs in genetic hypertension, we investigated the effect of OPB-9195, a novel inhibitor of AGEs, on hypertension and oxidative damage in SHRSP.MethodsFive-week-old male SHRSP were divided into a control group, fed a control diet and two, OPB-9195, (±)-2-isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide, treatment groups, fed a diet supplemented with OPB-9195 at the concentration of 0.5 (OPB-L) or 2 mg/g (OPB-H) mixed chow for 10 weeks.ResultsThe plasma of OPB-9195-treated SHRSP had lower levels of glycated albumin as compared with that of control SHRSP. OPB-9195 lowered the systolic blood pressure (SBP) by the fourth week of administration, and this effect was maintained throughout the study. We also confirmed SBP and diastolic blood pressure (DBP) rhythms, monitored by telemetry, were significantly lower in the OPB-H group than in the control group. Urinary nitric oxide (NO) excretion as well as the expression of endothelial NO synthase (eNOS) mRNA, and eNOS activity in the aorta were significantly increased in OPB-9195-treated groups compared with the control group. The levels of 8-hydroxydeoxyguanosine (8-OHdG), produced from deoxyguanosine under conditions of oxidative stress, in the urine of OPB-9195-treated SHRSP was significantly lower than in the control SHRSP. We also confirmed that the expression of glutathione peroxidase in the aorta was significantly increased in OPB-9195 treated SHRSP.ConclusionsBecause long-term administration of a AGEs inhibitor reduces blood pressure and oxidative damage in SHRSP, this study suggests a role for AGEs in the progression or maintenance of hypertension and related diseases in genetic hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveThe aims of this study were to assess the renal expression of angiotensin type 1 (AT1) and type 2 (AT2) receptors in diabetic spontaneously hypertensive rats (SHR) and the effect of AT1 receptor blockade on the expression of these receptors.DesignDiabetes was induced by injection of streptozotocin in SHRs. Irbesartan, an AT1 receptor antagonist, was given to diabetic SHRs for 32 weeks (15 mg/kg per day,n= 10). Diabetic (n= 10) and non-diabetic SHRs (n= 10) were studied concurrently. A separate group of control and diabetic Wistar–Kyoto (WKY) rats were also evaluated.MethodsGene and protein expressions of the AT1 and AT2 receptor were assessed by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry with specific antibodies andin vitroautoradiography with [125I]Sar(1), Ile(8)angiotensin II or [125I]CGP42112B.ResultsBoth AT1 and AT2 receptor mRNA levels in the kidney were reduced in diabetic SHRs compared to non-diabetic SHRs. Immunohistochemistry staining with specific antibodies showed a similar reduction in glomerular and tubulo-interstitial staining for both AT1 and AT2 receptors. Reduced binding for the AT1 and AT2 receptor was found in the kidney of diabetic SHRs. Diabetic SHRs developed albuminuria and had glomerular and tubulo-interstitial injury, which were prevented by treatment with irbesartan. Reduced expression of the AT1 receptor, but not the AT2 receptor, in diabetic SHRs was prevented by treatment with irbesartan. In diabetic WKY rats no such reduction in AT1 expression was observed, although there was a trend for reduced AT2 receptor expression.ConclusionsThese findings demonstrated that renal expression of both AT1 and AT2 receptor was reduced in long-term diabetic SHRs and that blockade of the AT1 receptor had disparate effects on expression of angiotensin II receptor subtypes.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo examine the relationship between heart rate variability (HRV) and baroreflex sensitivity (BRS).DesignAn observational study, with no intervention, in 55 volunteers with a wide range of arterial pressure (60–90/115–185 mmHg).MethodsVolunteers were studied first in the laboratory, with continuous measurement of systolic arterial pressure and electrocardiogram to obtain a frequency domain measure of baroreflex sensitivity (index α). Immediately afterwards, while the individual was ambulant, a Holter recording was obtained in order to compute time domain [standard deviation of consecutive normal R–R intervals (SDNN) and the percentage of successive R–R differences>50 ms (PNN50)], and frequency domain measures of HRV. Linear correlation was used to test the statistical link between index α and HRV indices.ResultsSignificant correlations were observed between index α and SDNN (r= 0.30;P<0.02) and PNN50 (r= 0.48;P<0.001), and between index α and total power (r= 0.53;P<0.001), and absolute powers of the 0.0001–0.04 Hz components of R–R interval variability in 24 h (r= 0.47;P<0.001).ConclusionThe major findings of this study are the clear demonstration of a significant correlation between a laboratory measure of baroreflex sensitivity and 24 h measures of HRV, obtained immediately afterwards. Notably, this correlation was found with both time domain and absolute, but not normalized, spectral measures of R–R interval variability. In addition, different levels of individual activity, as assessed by separate examination of daytime and night-time periods, did not seem to influence this relationship.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveLeptin induces increases in sympathetic nerve activity to various regions. This has implications for energy balance, thermogenesis and possibly cardiovascular regulation. The aim of the present study was to test the hypothesis that the increases in sympathetic nerve activity induced by leptin in different regions respond differentially to baroreflex activation.MethodsA total of 24 anesthetized male Sprague-Dawley rats were assigned to either leptin (0.5 mg/kg body weight bolus i.v., followed by 0.5 mg/kg body weight i.v. during 3 h,n= 12) or vehicle (n= 12) treatment. Mean arterial pressure (MAP), heart rate (HR), interscapular brown adipose tissue sympathetic nerve activity (IBAT-SNA) and renal sympathetic nerve activity (RSNA) were recorded continuously. Before and 3 h after start of leptin or vehicle, baroreceptor activity was decreased by lowering MAP with nitroprusside and increased by raising MAP with phenylephrine.ResultsCompared with vehicle, leptin significantly increased IBAT-SNA (294±78%) and RSNA (211±28%), while not altering MAP (117±5 versus 118±4 mmHg). Baroreflex activation by phenylephrine completely suppressed the leptin-induced increase in RSNA. In contrast, the leptin-induced increase in IBAT-SNA could not be overridden by baroreflex activation. Compared with vehicle, leptin did not significantly alter the maximum gain of the RSNA-MAP (−3.8±0.7 versus −2.7±0.3% of maximum mmHg−1, NS) or the IBAT-SNA-MAP curves (−1.9±0.7 versus −1.4±0.3% of maximum mmHg−1, NS).ConclusionsLeptin-induced regional increases in sympathetic nerve activity respond non-uniformally to baroreflex activation. The increase in RSNA can be suppressed by baroreflex activation, suggesting that the leptin-induced increase in RSNA subserves circulatory functions. In contrast, the increase in IBAT-SNA with leptin is not prevented by baroreflex activation, suggesting the recruitment of sympathetic fibers that serve thermogenic or metabolic and not circulatory functions.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

ObjectiveTo describe and compare the effects of six different antihypertensive medications on cognitive performance.DesignProspective, randomized, and double-blind with treatment cross-over.SettingUniversity hypertension clinic and neuropsychology laboratory.ParticipantsNinety-eight Caucasian men between 25 and 55 years of age with mild-to-moderate essential hypertension (88 of whom completed the study), and 32 normotensive men with similar socio-demographic characteristics.InterventionsSix-week treatment periods with atenolol, metoprolol, hydrochlorothiazide, methyldopa, enalapril and verapamil, and 2-week placebo baseline and wash-out periods.Main outcome measuresIn-depth neuropsychological assessments and several mood questionnaires were completed during placebo (baseline) periods and active treatment periods. Practice effects due to repeated neuropsychological testing were estimated from data collected concurrently in the normotensive participants.ResultsThe antihypertensive treatments lowered blood pressure comparably and did not affect mood or anxiety. Small treatment effects were noted in four of seven domains of cognitive performance. Irrespective of medication type, treatment reduced the simple motor speed (P<0.001), and slowed completion of two tests measuring perceptuo-motor speed and mental flexibility (P⩽ 0.05). Manual dexterity declined somewhat with metoprolol and methyldopa (P= 0.01). In contrast, all antihypertensive agents favorably affected performance on several tests that require working memory (P<0.01). Performance on other tests assessing grip strength, learning and memory, attention and executive function was not affected.ConclusionShort-term treatment with standard antihypertensive medications was associated with some small decrements in psychomotor performance and small improvements in working memory, without notable drug-class differences. Long-term effects await further study.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

BackgroundDose-ranging of antihypertensive agents have been done to optimize diastolic blood pressure (DBP) reduction, but with little information on systolic (SBP), mean (MBP), or pulse (PP) pressures. A low-dose combination of perindopril (Per) and indapamide (Ind) has been shown to reduce more SBP than atenolol for the same DBP reduction. However, the possible influence of gender on this finding has never been tested.PurposeA database of five randomized, double-blind, dose-ranging studies was established to determine the optimal dose of the Per/Ind combination in hypertensive men and women. A total of 2907 patients were treated by either placebo or various combinations associating Per (2, 4, 8 mg) and Ind (0.625, 1.25, 2.5 mg).ResultsIn the overall population, there was a significant dose–response relationship (P<0.001) for doubling the dose of Per 2/Ind 0.625 mg up to Per 8/Ind 2.5 mg with a progressive fall in SBP, DBP, MBP. When men and women were analyzed by dose, SBP, DBP and MBP (but not PP) decreased significantly more in women than in men until the Per 4/Ind 1.25 dosage was reached. Thereafter, with higher dosages, generating a slight but significant hypokalemia,the finding was reversed, resulting in a gender interaction in the overall population.ConclusionIn hypertensive subjects, the low-dose combinations Per 2/Ind 0.625 and Per 4/Ind 1.25 are the most effective in reducing blood pressure and avoiding hypokalemia. This effect is more pronounced in women, in which increased SBP and PP are predominant hemodynamic features.

ISSN:0263-6352    

出版商:OVID    

年代:2002

数据来源: OVID