ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

In the present study, we examined the relationships among carotid blood pressure, arterial geometry, and wall stress and determined the impact of hypertension, smoking status, and their interaction on these relationships. The study involved 679 subjects aged 49 to 82 years: 372 smokers (190 men and 182 women) and 307 nonsmokers (110 men and 197 women). Blood samples were taken to determine total cholesterol levels. Central pulse pressure was derived from measured brachial artery pressure with a linear regression equation from data obtained in a subgroup of 276 subjects that related brachial and carotid pulse pressures; the latter was measured with applanation tonometry. Carotid intima-media thickness (IMT), lumen diameter (D), and stiffness index (SI) were determined with high-resolution B-mode ultrasound. Mean and pulsatile circumferential stress (&sfgr;C) was calculated according to the Laplace relationship. Indexes of arterial geometry and function were adjusted for age, height, and heart rate. Hypertension (treated and/or screening blood pressure of >140/90 mm Hg) was present in 71 nonsmokers and 186 smokers. Nonsmokers and smokers did not differ in blood pressure and cholesterol levels. Hypertension and smoking individually and interactively significantly increased adjusted IMT, D, and SI. The radius-to–wall thickness ratio (R/IMT) (where R=D/2) and &sfgr;Cwere increased in hypertensives. SI was correlated with IMT (r=0.56,P<0.001); radius-to–wall thickness ratio was inversely correlated with central pulse pressure (r=−0.38,P<0.001). Smoking did not influence these relationships. In conclusion, carotid artery wall remodeling appears to follow Laplace’s law but is insufficient to prevent an increase in circumferential stress in hypertensive subjects. Unlike hypertension, smoking does not influence the lumen-to-wall ratio but has a significant effect on wall stiffness.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Blood pressure (BP) control rates around the world are suboptimal. Part 2 of the National Health and Nutrition Educational Survey (NHANES) III indicates that only 27.4% of hypertensive Americans aged 18 to 74 years have a BP of <140/90 mm Hg. We wanted to assess BP control during the first 2 years and to describe the baseline characteristics of patients enrolled in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) Study, an international clinical trial that compares outcomes in hypertensive patients randomized to initial treatment with either controlled-onset extended-release verapamil or the investigator’s choice of atenolol or hydrochlorothiazide. At randomization, BP was <140/90 mm Hg in only 20.3% of the 16 602 subjects (average±SD age 65.6±7.4 years; 56% women, 84% white/7% black/7% Hispanic). The average BP at enrollment was 148/85 mm Hg for patients taking BP medications (n=13 879) and 161/94 mm Hg for previously untreated patients (n=2723). After medication titration, with a transtelephonic computer that recommended an increase in the dose or number of antihypertensive agents whenever the BP was 140/90 mm Hg, 84.8% of the subjects attained the goal BP. During 2 years of treatment, BP control was maintained in 67% to 69% of the subjects (69% to 71% for systolic BP of <140 mm Hg and 90% for diastolic BP of <90 mm Hg). These data suggest that the control of systolic BP is more difficult than the control of diastolic BP. The US national goal of having 50% of hypertensives with a BP of <140/90 mm Hg may be achievable if a forced titration strategy is used. Interested investigators, free care and medications, and well-educated subjects may make the attainment of such a goal easier in the CONVINCE study than in the general population.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Diuretics and &bgr;-blockers have been shown to reduce the risk of cardiovascular morbidity and mortality in people with hypertension in long-term clinical trials. No study has compared newer more costly antihypertensive agents (calcium antagonists, ACE inhibitors, and &agr;-adrenergic blockers) with diuretics for reducing the incidence of cardiovascular disease in an ethnically diverse group of middle-aged and elderly hypertensive patients. The study is a randomized, double-blind, active-controlled clinical trial designed to determine whether the incidence of the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, differs between treatment initiation with a diuretic versus each of 3 other antihypertensive drugs. Men and women aged ≥55 years with at least 1 other cardiovascular disease risk factor were randomly assigned to chlorthalidone (12.5 to 25 mg/d), amlodipine (2.5 to 10 mg/d), lisinopril (10 to 40 mg/d), or doxazosin (2 to 8 mg/d) for planned follow-up of 4 to 8 years. This report describes the baseline characteristics of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants. A total of 42 448 participants were randomized from 625 sites in the United States, Canada, Puerto Rico, and the US Virgin Islands. The mean age was 67 years, with 35% aged ≥70 years. Among those randomized, 36% were black, 19% were Hispanic, and 47% were women. The sample includes a high proportion of people with diabetes (36%), patients with existing cardiovascular disease (47%), and smokers (22%). There were no important differences between the randomized treatment groups at baseline. ALLHAT will add greatly to our understanding of the management of hypertension by providing an answer to the following question: are newer antihypertensive agents similar, superior, or inferior to traditional treatment with diuretics?

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

To determine whether natriuretic peptides in addition to the renin-angiotensin system are involved in functional and structural vascular changes in salt-sensitive hypertension, we compared equipotent hypotensive treatment with the dual neutral endopeptidase/ACE inhibitor omapatrilat (35 mg · kg−1· d−1) or the ACE inhibitor captopril (100 mg · kg−1· d−1). The reactivity and geometry of mesenteric resistance arteries from Dahl salt-sensitive rats were studied in vitro under perfused and pressurized conditions. Chronic salt administration increased systolic blood pressure by 57±4 mm Hg, whereas concentrations of atrial natriuretic peptide were reduced in heart and in plasma (P<0.05). In addition, the medial cross-sectional area of small mesenteric arteries was increased and endothelium-dependent relaxation in response to acetylcholine and contraction in response to endothelin-1 were impaired in the mesenteric arteries of salt-sensitive rats on a high-salt diet (P<0.05). Concomitant treatment with either omapatrilat or captopril reduced the increase in systolic blood pressure and hypertrophic remodeling to a similar degree (P<0.05) but affected plasma and cardiac atrial natriuretic peptide levels differently (P<0.05). In addition, omapatrilat normalized endothelium-dependent relaxations to a greater extent than captopril (P<0.05). Furthermore, vasopeptidase inhibition increased cGMP levels compared with captopril (P<0.05). Contractions to endothelin-1 were normalized by either antihypertensive drug. These results suggest that in the Dahl rat, with similar reductions in systolic blood pressure, omapatrilat is superior to captopril in preventing impaired endothelial function in small resistance arteries. Thus, vasopeptidase inhibition may have therapeutic advantages of the prevention of changes in vascular function and structure in salt-sensitive forms of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Recent studies have suggested that part of the vasorelaxation caused by nifedipine, a 1,4-dihydropyridine Ca2+antagonist, depends on the endothelium. To study the effect of endothelium-dependent vasorelaxation, the release of NO and superoxide (O2−) in the presence of nifedipine in isolated cultured rabbit endothelial cells was measured. Highly sensitive electrochemical microsensors were placed onto the cell membrane, and the kinetics of NO and O2−were measured simultaneously with time resolutions of 0.1 and 0.05 ms, respectively. Nifedipine at its therapeutical concentrations stimulated NO release and scavenged O2−in endothelial cells. The linear relationship between NO concentration and nifedipine concentration was observed in the range between 0.01 and 1 nmol/L. NO concentration reached a maximum of 200±10 nmol/L at 1.2 nmol/L of nifedipine. The NO concentration was ≈50% and 30% of the concentration measured in the presence of receptor-dependent (acetylcholine) and the receptor-independent (Ca2+ionophore A23187) NO synthase (eNOS) agonists, respectively. NO release stimulated by eNOS agonists was followed by the generation of the NO scavenger superoxide. The concentration of O2−was significantly lower after stimulation with nifedipine (peak 5±0.5 nmol/L) than after stimulation with acetylcholine (15±1 nmol/L) and Ca2+ionophore (25±1 nmol/L). The average rate of NO release by nifedipine is relatively slow (17 nmol/L per second). This is in sharp contrast to the fast rate of NO release by acetylcholine and Ca2+ionophore (40 and 300 nmol/L per second, respectively). These experiments show that nifedipine, apart from its well-known Ca2+antagonistic properties in vascular smooth muscle cells, stimulates the release of significant concentration of NO in endothelium and also preserves NO concentration. Both these effects may be beneficial in the treatment of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

To evaluate whether ACE inhibition and angiotensin II type 1 blockade exert beneficial effects on NO availability independent of their blood pressure–lowering effect, we used a double-blind crossover design to study vascular function in 18 patients with hypertensive renovascular disease during 6 weeks of therapy with enalapril (Ena) and valsartan (Val) compared with non–renin-angiotensin system–mediated treatment with the &agr;1-blocker doxazosin (Dox). Control measurements were performed in 13 age-matched volunteers. Forearm blood flow was assessed with venous occlusion plethysmography, and serotonin and nitroprusside were used as endothelium-dependent and -independent vasodilators, respectively. Blood pressure was similar during all treatment periods. Serotonin-induced vasodilation was decreased in patients during Dox treatment (n=12) compared with control subjects (n=13) (increase 42±20% versus 107±65%,P<0.05). Crossover from Dox to Val (n=6) had no effect on serotonin response (increase 50±14%), but crossover to Ena (n=6) caused a significant improvement (increase 79±39%,P<0.05 versus Dox). In an assessment of all patients, serotonin-induced vasodilation during Ena (n=12, increase 75±31%) was increased compared with both Val and Dox (43±14% and 42±20%, respectively; bothP<0.05 versus Ena). The nitroprusside response remained unaltered during all treatment periods. In conclusion, ACE inhibition improves the impaired endothelium-dependent vascular function in patients with hypertensive renovascular disease. This effect is unrelated to blood pressure–lowering or angiotensin II–mediated effects.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Bradykinin is a potent endothelium-dependent vasodilator that contributes to the blood pressure lowering effect of angiotensin-converting enzyme inhibition. Angiotensin-converting enzyme inhibitors are widely prescribed for the treatment of hypertension, although the efficacy of this therapy has been reported to vary among different ethnic groups. To determine whether vascular sensitivity to bradykinin is decreased in blacks compared with whites, we measured forearm blood flow with venous plethysmography in response to intraarterially-administered bradykinin (100, 200, and 400 ng/min) under salt-controlled conditions in 28 (14 black, 14 white) normotensive subjects genotyped for theACEinsertion/deletion (I/D) polymorphism. Acetylcholine (ACh) (15, 30, and 60 &mgr;g/min) and sodium nitroprusside (SNP) (0.8, 1.6, and 3.2 &mgr;g/min) were infused as endothelium-dependent and endothelium-independent controls. Compared with whites, blacks exhibited a blunted vasodilator response to bradykinin (maximal blood flow: 20.4±2.5 versus 10.9±1.4 mL · 100 mL−1· min−1,P=0.004) and SNP (14.1±1.6 versus 9.9±1.7 mL · 100 mL−1· min−1,P=0.05) but not to ACh (10.5±2.8 versus 6.6±1.0 mL · 100 mL−1· min−1,P=0.21). White subjects who carried at least 1ACE Dallele demonstrated significantly greater vasodilator responses to bradykinin compared with those homozygous for theIallele (DDorIDversusII, F=5.6,P<0.04). In contrast, only blacks homozygous for theACE Dallele had a significantly greater vasodilator response to bradykinin than those who carried theIallele (DDversusIDorII, F=8.3,P=0.01). The ethnic difference was most pronounced in subjects heterozygous at theACE I/Dlocus in which blacks had a markedly attenuated response to bradykinin compared with whites (F=41.0,P<0.001). There was no effect ofACE I/Dgenotype on the vasodilator responses to SNP or ACh in either ethnic group. These data confirm that vascular reactivity to bradykinin and the endothelium-independent vasodilator SNP is decreased in normotensive blacks compared with whites, consistent with attenuated vascular smooth muscle reactivity. The data suggest that genetic variation at theACEgene locus interacts with ethnicity to impact the vascular response to bradykinin.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Mitogen-activated protein (MAP) kinases have been shown to be activated by various growth factors in cultured or isolated cardiomyocytes. However, little is known about the regulation of MAP kinases in vivo, especially in clinically important conditions, such as hypertension and senescence. In this study, we assessed mechanical overload–induced activation of myocardial MAP kinases in beating hearts from hypertensive or senescent rats. Fifteen minutes of left ventricular hemodynamic overload activated MAP kinase activity by 2.2-fold (P<0.05) in 4-week-old Wistar-Kyoto rats. The age-matched spontaneously hypertensive rats had greater MAP kinase activity than did Wistar-Kyoto rats both at baseline (1.4 times,P<0.05) and after the hemodynamic overload (1.7 times,P<0.05). Myocardial MAP kinase protein level, assessed by Western blot analysis, was also higher (1.6 times,P<0.01) in spontaneously hypertensive rats. In contrast, aged (18-month-old) Fischer 344 rats, which were known to have a diminished capacity of hypertrophy in response to mechanical stress, had lower MAP kinase activity both at baseline (63%,P<0.01) and after the hemodynamic overload (52%,P<0.05). Their MAP kinase protein level was lower (38%,P<0.01) than that in young (6-month-old) adults. Alterations in MAP kinase may contribute to changes in hypertrophic response in these animals.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Intercellular adhesion molecule-1 (ICAM-1), part of an immunoglobulin-like superfamily of adhesion molecules, is involved in several cardiovascular diseases. We investigated whether in vivo angiotensin II (Ang II) increases ICAM-1 in rats. Sprague-Dawley rats were infused with vehicle or Ang II (750 &mgr;g · kg−1· d−1SC) for 7 days. The contribution of Ang II receptors to ICAM-1 expression was investigated with a nonpeptide Ang II type 1 (AT1) receptor antagonist losartan (30 mg · kg−1· d−1in drinking water). Systolic blood pressure was elevated in Ang II–treated animals compared with sham-treated controls, and losartan blocked this increase. Tumor necrosis factor (TNF)-&agr; (5 &mgr;g/kg IP bolus), a prototype inducer of ICAM-1, was administered as a positive control for ICAM-1 expression. After treatment, hearts were frozen in liquid nitrogen; homogenates were subjected to SDS-PAGE and immunoblotted with an anti-rat ICAM-1 monoclonal antibody. We detected a predominantly high-molecular-weight band in homogenates from non–TNF-&agr;–treated rats, which was enhanced by 80±5% in TNF-&agr;–treated rats. This band measured ≈200 kDa, which is the molecular weight of ICAM-1 in its native dimer form. The same band was detected in homogenates from sham and Ang II–treated rats, with the latter showing a 150±10% increase in ICAM-1 versus sham controls. Immunoprecipitation of rat heart homogenates with anti-rat ICAM-1 antibody resulted in a dominant band of the same molecular weight as samples not treated with antibody. Losartan prevented enhanced expression of ICAM-1 in the presence of Ang II but had no effect on basal ICAM-1 expression. Phenylephrine, an &agr;-agonist (3 mg · kg−1· d−1), was infused for 1 week but had no effect on ICAM-1 expression, even though systolic blood pressure was elevated to the same level as in rats treated with Ang II. Thus, heart ICAM-1 expression is enhanced via AT1receptor activation independent of hypertension. Ang II–induced ICAM-1 expression was time and dose dependent, with maximal expression occurring within 5 to 7 days at 100 to 750 &mgr;g/kg Ang II. Immunohistochemical staining demonstrated markedly increased ICAM-1 levels in the perivascular area in Ang II–infused rats. Monocyte/macrophage accumulation was significantly greater in Ang II–treated rat hearts than in sham-treated hearts (10±1;P<0.001; n=5). Thus during inflammation, overexpression of ICAM-1 may contribute to cardiovascular damage in diseases characterized by increased activity of the renin-angiotensin system.

ISSN:0194-911X    

出版商:OVID    

年代:2001

数据来源: OVID