摘要:

Abstract—Obesity is an important risk factor for hypertension; however, the pathway through which it raises blood pressure (BP) is poorly understood. Body size is also the primary determinant of energy expenditure, and we therefore examined the joint relationship of energy expenditure and body size to blood pressure. Resting energy expenditure (REE) was measured using respiratory gas exchange in population-based samples of 997 Nigerians and 452 African Americans. In a third sample of 118 individuals, nonresting energy expenditure (ie, physical activity) was measured in addition to REE. The univariate correlation between REE and BP ranged from 0.10 to 0.22 in the 3 samples (P<0.001). In multivariate models, adiposity, whether defined by body mass, fat mass, or leptin, was no longer associated with BP, while REE remained highly significant (P<0.001). The REE–BP association also persisted after adjustment for physical activity measured with doubly labeled water. The odds ratio for hypertension among persons in the highest quartile versus the lowest quartile of REE, after adjustment for body size, was 1.7. This relationship was not the result of hypertension among the obese, because it did not vary across the range of BMI and was the same in lean Nigerians as in obese Americans. These data suggest that metabolic processes represented by REE may mediate the effect of body size on BP. The interrelationship of REE with sympathetic tone, transmembrane ion exchange, or other metabolic processes that determine energy costs at rest could provide physiological explanations for this observation.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Structural alterations of small resistance arteries in patients with essential hypertension (EH) are mostly characterized by inward eutrophic remodeling. However, we have observed the presence of hypertrophic remodeling in patients with renovascular hypertension, as well as in patients with noninsulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure. Growth hormone may stimulate in vitro proliferation of vascular smooth muscle cells. However, no data are presently available about small artery structure in acromegalic patients. Therefore, we have investigated the structure of subcutaneous small arteries in 12 normotensive (NT) subjects, in 12 EH subjects, and in 9 acromegalic patients (APs). All subjects underwent biopsy of the subcutaneous fat; then, small resistance arteries were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media-to-lumen ratio, the media cross-sectional area together with remodeling, and growth indices were calculated. Demographic variables were similar in the three groups, except for blood pressure. The media-to-lumen ratio was significantly greater in EH and AP, compared with NT. No difference was observed between EH and AP. The media cross-sectional area was significantly greater in AP compared with EH and with NT. The calculation of remodeling and growth index suggests the presence of eutrophic remodeling in EH (growth index 0%) and of hypertrophic remodeling in AP (growth index 40%). In conclusion, our data suggest the presence of hypertrophic remodeling of subcutaneous small resistance arteries of AP, probably as a consequence of growth-stimulator properties of IGF-1.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—On average, whites and blacks differ in their response to specific antihypertensive drugs. These differences are often highlighted in reviews and practice guidelines. However, there is wide variation in drug-associated changes in blood pressure within each race. The goal of this meta-analysis is to quantitate how often whites and blacks have similar responses to specific antihypertensive drugs. Computerized searches of MEDLINE (1983 to March 2003) and manual searches of references listed in identified articles were performed. Studies were included if they provided race-specific changes in blood pressure. Fifteen studies with a total of 9307 white subjects and 2902 black subjects were analyzed. For drug-associated changes in diastolic blood pressure, the mean difference between whites and blacks ranged from 0.6 to 3.0 mm Hg while the standard deviation within each race ranged from 5.0 to 10.1 mm Hg. The percentage of whites and blacks with similar drug-associated changes in diastolic blood pressure was 90% (95% confidence interval: 81 to 99) for diuretics, 90% (95% CI: 83 to 97) for &bgr;-blockers, 95% (95% CI: 92 to 98) for calcium channel blockers, and 81% (95% CI: 76 to 86) for angiotensin converting enzyme inhibitors. The percentage of whites and blacks with similar drug-associated changes in systolic blood pressure ranged from 83% to 93%. In conclusion, the majority of whites and blacks have similar responses to commonly used antihypertensive drugs. Clinical decisions to use a specific drug should be based on other considerations such as efficacy in individual patients, compelling indications, and cost.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Cyclo-oxygenase (COX) inhibitors attenuate the antihypertensive effects of angiotensin-converting enzyme (ACE) inhibitors and reduce kidney function. The study tests the hypothesis that these two classes of drugs have similar effects on glomerular filtration rate (GFR) and 24-hour blood pressure. The primary endpoint was change in 24-hour systolic blood pressure. Using a randomized crossover design, 25 black and Hispanic hypertensive participants (mean age 58±3 years) with osteoarthritis were studied. All participants received an ACE inhibitor at baseline. Once systolic blood pressure was <140 mm Hg, either celecoxib 200 mg/d or diclofenac 75 mg twice daily for 4 weeks was started. After measurements were obtained, all participants underwent a 2-week washout period and crossed over to the other drug for 4 weeks. A significant difference in mean 24-hour systolic blood pressure was noted between groups at 4 weeks (+4.1±1.1 mm Hg diclofenac versus +0.6±0.6 mm Hg celecoxib;P=0.01). However, because celecoxib has duration of action shorter than 24 hours, we compared ambulatory values at celecoxib trough and peak activities. At peak, no difference in systolic blood pressure was noted between agents (+3.6±0.04 mm Hg diclofenac versus +4.2±1.9 mm Hg celecoxib;P=0.67). GFR was also differentially affected at 24 hours (−9.9±2.4 mL/min diclofenac versus −0.4±1.2 mL/min celecoxib;P=0.01). We conclude that diclofenac and celecoxib increase systolic blood pressure at peak levels; however, these agents differ in their 24-hour effects. Differences observed in blood pressure response between COX inhibitors may not be related in their sensitivity but rather their dosing frequency.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—We studied factors associated with awareness, treatment, and control of hypertension (systolic/diastolic blood pressure measurements ≥140/90 mm Hg, respectively, and/or current drug treatment for hypertension) in a representative sample of the Chinese population (n=15 838). Awareness, treatment, and control were defined by self-report of a hypertension diagnosis, self-report of current antihypertensive medication use, and a systolic and diastolic blood pressure <140/90 mm Hg, respectively. Higher awareness (OR; 95% CI) was noted for persons who were married (1.43; 1.09, 1.88) and had their blood pressure measured in 1 year (47.4; 31.7, 70.4) or 1 to 5 years (11.4; 7.09, 18.2) preceding their study visit; lower awareness was found among men (0.62; 0.52, 0.74) and current smokers (0.79; 0.63, 0.99). Among those aware of their hypertension, treatment was more common (OR; 95% CI) at higher income (1.24 [0.87, 1.75], 1.46 [1.01, 2.12] and 1.58 [1.06, 2.37] for increasing versus the lowest quartile of income) and for participants who had their blood pressure measured during the preceding year (3.87; 1.89, 7.93) and was less common among men (0.76; 0.59, 0.98). Controlled hypertension was more common (OR; 95% CI) among persons whose blood pressure had been measured 1 year (4.93; 1.51, 16.1) and 1 to 5 years (14.8; 3.63, 60.5) prior to their study visit and, among persons aware of their hypertension diagnosis, those who undertook lifestyle modification (1.59; 1.11, 2.27). These data identify potential methods for improving blood pressure control in China through the identification, follow-up, and lifestyle modification of persons with high blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—The physiological adaptation to the erect posture involves integrated neural and cardiovascular responses that might be determined by genetic factors. We examined the familial- and individual-specific components of variance for postural changes in systolic and diastolic blood pressure in 767 volunteer nuclear adult families from the Victorian Family Heart Study. In 274 adult sibling pairs, we made a genome-wide scan using 400 markers for quantitative trait loci linked with the postural changes in systolic and diastolic pressures. Overall, systolic pressure did not change on standing, but there was considerable variation in this phenotype (SD=8.1 mm Hg). Familial analyses revealed that 25% of the variance of change in systolic pressure was attributable to genetic factors. In contrast, diastolic pressure increased by 6.3 mm Hg (SD=7.0 mm Hg) on standing and there was no evidence of contributory genetic factors. Multipoint quantitative genome linkage mapping suggested evidence (Z=3.2) of linkage of the postural change in systolic pressure to chromosome 12 but found no genome-wide evidence of linkage for the change in diastolic pressure. These findings suggest that genetic factors determine whether systolic pressure decreases or increases when one stands, possibly as the result of unidentified alleles on chromosome 12. The genetics of postural changes in systolic blood pressure might reflect the general buffering function of the baroreflex; thereby, the predisposition to sudden decreases or increases in systolic pressure might cause postural hypotension or vessel wall disruption, respectively.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—In a genome-wide scan in Scandinavians, we found suggestive linkage between early-onset primary hypertension and a region on chromosome 2. The &agr;2B-adrenoceptor gene, a candidate gene within this region, harbors a functional insertion/deletion (I/D) polymorphism of three glutamate residues. The aim of this study was to investigate if the DD genotype is associated with hypertension in Swedes. We performed an association study between the I/D polymorphism of the &agr;2B-adrenoceptor and hypertension in the Skaraborg population. The material consists of all known patients with primary hypertension in Skara (n=772 nondiabetic subjects; n=171 normoalbuminuric type 2 diabetic subjects) and 817 population control subjects. We first compared genotype frequencies between patients with early-onset hypertension (aged 50 years or younger at onset) and subjects with normotension (blood pressure <120/80 mm Hg). Thereafter, the polymorphism was tested for association with hypertension at the population level. When comparing patients with early-onset hypertension and normotensive subjects, the DD versus II genotype was associated with early-onset hypertension when diabetic subjects were excluded from the analysis (OR=2.0; 95% CI=1.2 to 3.5) or when they were not excluded (OR=1.8; 95% CI=1.0 to 3.1). At the population level, the DD versus II genotype was weakly associated with nondiabetic hypertension (OR=1.4; 95% CI=1.0 to 1.8). Our data suggest that carriers of the DD versus II genotype of the &agr;2B-adrenoceptor are at increased risk for hypertension. The genotypic effect is most evident when comparing groups corresponding to the upper and lower tails of the blood pressure distribution in the population; however, in nondiabetic hypertensive subjects it is weakly detectable even at the population level.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Genes of the renin-angiotensin–aldosterone system (RAAS) are natural candidates for sodium homeostasis and blood pressure regulation. To investigate the effect of a combination of polymorphisms of RAAS genes on renal sodium handling and blood pressure, 918 participants to the Olivetti Heart Study were genotyped for the following polymorphisms: I/D of angiotensin converting enzyme (ACE), M235T of angiotensinogen (AGT), A1166C of angiotensin II type-1 receptor (AT1R), and C-344T of aldosterone synthase (CYP11B2). The segmental renal sodium handling was evaluated by the fractional excretions of exogenous lithium (FE-Li), uric acid (FE-UA), and sodium (FE-Na). Twenty-eight carriers of triple homozygosity for M (AGT), A (AT1R), and C (CYP11B2) in the presence of the D allele ofACE(DD/ID) showed lower FE-Li (20.0%±5.9% versus 25.0%±7.5%;P=0.004; mean±sD), FE-UA (6.3%±2.0% versus 8.2%±2.7%;P=0.001), and FE-Na (0.96%±0.41% versus 1.22%±0.61%;P=0.004) as compared with all other allelic combinations (n=890), independently from age and body mass, suggesting an enhanced rate of proximal tubular sodium reabsorption. The carriers of the MM, AA, CC, DD/ID combination showed a substantially higher probability of being hypertensive (OR: 3.4 [(99% CI: 1.1 to 10.1]), independently of age and body mass. This relatively rare combination of allelic variants of candidate genes of the RAAS is associated with a significant alteration in proximal renal sodium handling and with higher risk of hypertension, suggesting that a combination of polymorphic variants at different candidate loci may affect phenotypic expression even in the absence of detectable effects of each variant at any single locus.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Although the angiotensin-converting enzyme (ACE) inhibitor-induced bradykinin enhances nitric oxide (NO) release, bradykinin may also stimulate the production of an additional vasodilator, endothelium-derived hyperpolarizing factor (EDHF). This study examined the role of EDHF in mediating the NO-independent action of ACE inhibitors in canine renal microcirculation in vivo. We used intravital CCD camera videomicroscopy that allowed direct visualization of renal microcirculation in superficial and juxtamedullary nephrons in an in vivo, in situ, and relatively intact setting. In the presence of E4177 (an angiotensin receptor blocker), cilazaprilat (30 &mgr;g/kg) had no effect on diameter of superficial afferent arterioles (Aff), but it increased renal contents of bradykinin and nitrate plus nitrite, and it elicited dilation of juxtamedullary Aff (from 24.0±0.2 to 28.2±0.8 &mgr;m), juxtamedullary efferent arterioles (Eff) (from 24.2±0.2 to 28.0±0.8 &mgr;m), and superficial Eff (from 18.2±0.2 to 19.7±0.2 &mgr;m). These changes in diameters were prevented by N&agr;-adamantaneacetyl-d-Arg-[Hyp3,Thi5,8,D-Phe7]bradykinin, a bradykinin receptor antagonist. The pretreatment with nitro-l-arginine methylester (l-NAME) plus E4177 eliminated the dilator response of juxtamedullary/superficial Eff and the increase in renal nitrate plus nitrite levels induced by cilazaprilat. In contrast, in the presence of E4177+l-NAME, cilazaprilat still caused 8%±3% dilation of juxtamedullary Aff, which was completely eliminated by proadifen, a cytochrome-P450 and KCachannel blocker. Collectively, the ACE inhibitor exerts multiple vasodilator mechanisms, including the inhibition of angiotensin II formation; blockade of angiotensin II activity appears to be a dominant mechanism in superficial Aff, whereas the bradykinin-induced NO acts on superficial Eff and juxtamedullary Aff/Eff. Furthermore, a putative EDHF is an additional mechanism for the ACE inhibitor-induced vasodilation of juxtamedullary Aff in vivo.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—The association between low birth weight and high blood pressure is well established, but underlying mechanisms remain undefined. Vascular rarefaction, which may elevate peripheral vascular resistance, has been observed in capillaries of young men at risk for hypertension and men who had low birth weight. We looked for evidence that capillary rarefaction explains the association of low birth weight with high blood pressure in two cohorts. Participants in study 1 included 107 healthy boys aged 6 to 16 years recruited at random from a single school. Study 2 included 61 members of a cohort recruited at birth and studied at age 24 years. Measurements included indices of current size, blood pressure by automated sphygmomanometer, and dermal capillary density by video capillaroscopy of dorsal index finger skin after 10 minutes of venous occlusion. Lower birth weight predicted higher systolic blood pressure in both studies: in study 1, 3.57 mm Hg/kg birth weight (after adjustment for current height, 95% confidence interval 0.38 to 6.75,P<0.05); in study 2, 122±12 mm Hg in low birth weight (<2 kg) versus 115±9 in controls (P<0.05). Dermal capillary density was not associated in either group with birth weight or systolic blood pressure. We have found no evidence in these 2 cohorts that reduced capillary density explains the associations between lower birth weight and higher blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID