ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Thiazide diuretics are one of the preferred pharmacologic treatments for hypertension. Hydrochlorothiazide and chlorthalidone have been the 2 most commonly used diuretics in major clinical trials. Treatment guidelines and compendia often consider these 2 drugs interchangeable agents within the class of thiazide or thiazide-like diuretics. Many sources list them as equipotent. Despite these beliefs, there is some suggestion that cardiovascular outcomes are not necessarily the same with these 2 drugs. We conducted a literature search from 1960 to 2003 to identify studies that evaluated the pharmacokinetic and blood pressure–lowering effects of these 2 agents. There are significant pharmacokinetic and pharmacodynamic differences between these diuretics. Chlorthalidone is ≈1.5 to 2.0 times as potent as hydrochlorothiazide, and the former has a much longer duration of action. Whether these pharmacokinetic and pharmacodynamic features cause differences in outcomes is not known.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Levels of hypertension treatment and control have been noted to vary between Europe and North America, although direct comparisons with similar methods have not been undertaken. In this study, we sought to estimate the relative impact of hypertension treatment strategies in Germany, Sweden, England, Spain, Italy, Canada, and the United States by using sample surveys conducted in the 1990s. Hypertension was defined as a blood pressure of 160/95 mm Hg or 140/90 mm Hg, plus persons taking antihypertensive medication. “Controlled hypertension” was defined as a blood pressure less than threshold among persons taking antihypertensive medications. Among persons 35 to 64 years, 66% of hypertensives in the United States had their blood pressure controlled at 160/95 mm Hg, compared with 49% in Canada and 23% to 38% in Europe. Similar discrepancies were apparent at the 140/90 mm Hg threshold, at which 29% of hypertensives in the United States, 17% in Canada, and ≤10% in European countries had their blood pressure controlled. At the 140/90 mm Hg cutpoint, two thirds to three quarters of the hypertensives in Canada and Europe were untreated compared with slightly less than half in the United States. Although guidelines vary among countries, resulting in different case definitions, this does not account entirely for the varying success of different national control efforts. Low treatment and control rates in Europe, combined with a higher prevalence of hypertension, could contribute to a higher burden of cardiovascular disease risk attributable to elevated blood pressure compared with that in North America.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—High blood pressure (BP) is common in acute stroke and might be associated with a poor outcome, although observational studies have given varying results. In a systematic review, articles were sought that reported both admission BP and outcome (death, death or dependency, death or deterioration, stroke recurrence, and hematoma expansion) in acute stroke. Data were analyzed by the Cochrane Review Manager software and are given as odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs). Altogether, 32 studies were identified involving 10 892 patients. When all data were included, death was significantly associated with an elevated mean arterial BP ([MABP] OR, 1.61; 95% CI, 1.12 to 2.31) and a high diastolic BP ([DBP] OR, 1.71; 95% CI, 1.33 to 2.48). Combined death or dependency was associated with high systolic BP ([SBP] OR, 2.69; 95% CI, 1.13 to 6.40) and DBP (OR, 4.68; 95% CI, 1.87 to 11.70) in primary intracerebral hemorrhage (PICH). Similarly, high SBP (+11.73 mm Hg; 95% CI, 1.30 to 22.16), MABP (+9.00 mm Hg; 95% CI, 0.92 to 17.08), and DBP (+6.00 mm Hg; 95% CI, 0.19 to 11.81) were associated with death or dependency in ischemic stroke. Combined death or deterioration was associated with a high SBP (OR, 5.57; 95% CI, 1.42 to 21.86) in patients with PICH. In summary, high BP in acute ischemic stroke or PICH is associated with subsequent death, death or dependency, and death or deterioration. Moderate lowering of BP might improve outcome. Acute BP lowering needs to be tested in 1 or more large, randomized trials.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Prospective studies on physical activity in relation to the risk for hypertension are scant, particularly in women. This study aimed at finding out whether regular physical activity can reduce the risk of hypertension in both men and women, and in subjects with and without overweight. We prospectively followed 8302 Finnish men and 9139 women aged 25 to 64 years without a history of antihypertensive drug use, coronary heart disease, stroke, and heart failure at baseline. Both single and joint associations of physical activity and body mass index with the risk of hypertension were examined using Cox proportional hazard models. During a mean followup of 11 years, there were 1600 incident cases of drug-treated hypertension. Multivariate-adjusted hazards ratios of hypertension associated with light, moderate, and high physical activity were 1.00, 0.63, and 0.59 in men (Ptrend<0.001), and 1.00, 0.82, and 0.71 in women (Ptrend=0.005), respectively. This association persisted both in subjects who were overweight and in those who were not. Multivariate-adjusted hazards ratios of hypertension based at different levels of body mass index (<25, 25 to 29.9, and ≥30) were 1.00, 1.18, and 1.66 for men (Ptrend<0.001), and 1.00, 1.24, and 1.32 for women (Ptrend=0.007), respectively. Further adjustment for baseline systolic blood pressure did not affect the protective effect associated with physical activity, but it weakened markedly the association between body mass index and hypertension. The present study indicates that regular physical activity and weight control can reduce the risk of hypertension. The protective effect of physical activity was observed in both sexes regardless of the level of obesity.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Black Americans have a reduced hypotensive response to the &agr;2-adrenergic receptor agonist clonidine compared with whites, despite similar central sympathoinhibition. This reduced hypotensive response might be explained by greater postsynaptic vascular &agr;2-adrenergic receptor vasoconstrictive response. However, clonidine has a low &agr;2/&agr;1selectivity ratio. Therefore, to determine the role of altered &agr;2-adrenergic receptor vascular sensitivity in ethnic differences in vascular response, we compared local vascular responses with the highly selective &agr;2-adrenergic receptor agonist dexmedetomidine in healthy black (n=18) and white (n=19) subjects. Increasing doses of dexmedetomidine (0.001 to 1000 ng/min) were infused into a dorsal hand vein, and the local response was measured with a linear variable differential transformer. Dexmedetomidine caused pronounced venoconstriction, with an average (±SD) maximum response of 74.5±17.72% but with no difference between blacks and whites. There was substantial intersubject variability in the sensitivity to dexmedetomidine; the dose resulting in 50% (ED50) of maximum vasoconstriction ranged from 0.08 ng/min to 256 ng/min. The geometric mean ED50was 2.28 ng/min (95% CI, 0.02 to 271.6 ng/min) in blacks and 1.58 ng/min (95% CI, 0.11 to 24.55 ng/min) in whites (P=0.59). Our data indicate that &agr;2-adrenergic receptor–induced venoconstriction is similar in blacks and whites. These findings do not support the hypothesis that altered &agr;2-adrenergic receptor sensitivity is the explanation for the decreased blood pressure response to systemic administration of clonidine in blacks. The response to dexmedetomidine provides a model that will allow further study of the regulation of &agr;2-adrenergic receptor–mediated vascular responses

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Hypertensive patients have increased endothelin-1–dependent vasoconstrictor tone. This abnormality, however, might not be uniformly present in all forms of hypertension, as suggested by experimental studies showing that endothelin-1 activity is enhanced predominantly in low-renin, high-volume models and in insulin-resistant states. Because hypertension in obesity is commonly associated with both expanded plasma volume and insulin resistance, this study sought to determine whether increased body mass index (BMI) in hypertensive patients relates to activation of the endothelin-1 system. Forearm blood flow (FBF) responses (plethysmography) to intra-arterial infusion of an ETAreceptor blocker (BQ-123) were analyzed in hypertensive patients and normotensive control subjects according to BMI. The vasodilator response to BQ-123 was significantly higher in hypertensive patients than in control subjects (P<0.001). During BQ-123, a significant increase in FBF from baseline was observed in obese (BMI ≥30 kg/m2;P<0.001) and overweight (BMI, 27 to 29.9 kg/m2;P=0.04) but not in lean (BMI <27 kg/m2;P=0.83) hypertensive patients. In contrast, no significant change in FBF was observed during BQ-123 either in obese (P=0.53), overweight (P=0.76), or lean (P=0.93) normotensive subjects. Moreover, a significant correlation between BMI and the vasodilator response to ETAblockade was observed in hypertensive subjects (R=0.53;P=0.005) but not in control subjects (R=0.11;P=0.58). In human hypertension, increased BMI is associated with enhanced ETA-dependent vasoconstrictor activity, suggesting that this abnormality may play a role in the pathophysiology of obesity-related hypertension and that targeting the endothelin-1 system may be useful in the treatment of these patients.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—This study examined the importance of aldosterone (ALDO) in mediating changes in renal function and increased mean arterial pressure (MAP) during the development of dietary-induced obesity in chronically instrumented dogs. Mean arterial pressure, heart rate (HR), and cardiac output (CO) were recorded 24 hours per day in lean dogs (n=7) before and after administration of an ALDO antagonist, eplerenone (EP) (10 mg/kg twice daily), for 10 days. After 10 days of EP treatment, the dogs (n=7) were given a supplement of cooked beef fat for 5 weeks while EP was continued. An untreated group (n=6) was fed a high fat diet for 5 weeks and used as control (C). In lean dogs, EP decreased MAP from 89±4 to 84±4 mm Hg and glomerular filtration rate from 67.4±6.8 to 53.2±4.9 mL/min while inducing a small negative Na+balance (−42±12 mEq). Plasma renin activity increased from 0.4±0.1 to 2.7±0.7 ng AI/mL per hour and plasma K+increased from 4.8±0.1 to 6.1±0.3 mEq/L. After 5 weeks of a high fat diet, body weight increased 45% to 53% in EP and C obese dogs. In C dogs, MAP increased by 16±3 mm Hg, compared with only 7±1 mm Hg in EPLE dogs. Compared with untreated dogs, the EP dogs had smaller increases in CO (18±4.6% versus 43±1.5%), HR (33±5% versus 60±3%), glomerular filtration rate (19±5% versus 38±6%), and cumulative Na+balance (138±35 mEq versus 472±110 mEq) after 5 weeks of a high fat diet. Thus, EP markedly attenuated glomerular hyperfiltration, sodium retention, and hypertension associated with chronic dietary-induced obesity. These observations indicate that ALDO plays an important role in the pathogenesis of obesity hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—The objective of this study was to determine the effect of pioglitazone on blood pressure (BP) and oxidative balance in obese, hypertensive, Sprague-Dawley rats and to identify some of the molecular mechanisms involved. After 12 weeks of a moderately high-fat diet, rats diverged into obesity-prone (OP) and obesity-resistant (OR) groups (n=6 per group). At the end of the diet, peroxisome proliferator activated receptor-&ggr; (PPAR&ggr;) mRNA expression and activity in the renal cortex and medulla of OP rats were significantly lower compared with that in OR rats. Pioglitazone treatment increased PPAR&ggr; expression and activity in OP rats, suggesting a possible direct ligand-related effect of pioglitazone. As opposed to the untreated OP group, which showed moderate hypertension (systolic BP=159±5.3 mm Hg) after 12 weeks, pioglitazone-treated rats were normotensive (systolic BP=123.9±2.7 mm Hg). Insulin production was reduced by 2-fold in the OP group treated with pioglitazone. Urinary isoprostanes and renal lipid peroxides were also reduced in OP rats treated with pioglitazone compared with untreated counterparts. Also, expression of p47phoxand gp91phox, both increased in OP versus OR rats, was reduced in the former by pioglitazone treatment. In addition, pioglitazone treatment increased nitrate/nitrite excretion and expression of renal endothelial and neuronal nitric oxide synthase. Collectively, the results show that pioglitazone treatment prevented hypertension and renal oxidative stress both by reducing free-radical production and by increasing nitric oxide production/availability.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID