摘要:

Drug treatment of hypertension reduces systolic and diastolic blood pressure according to a well-established dose–response curve. Whether there is a parallel decrease in mean blood pressure and pulse pressure has not been investigated in the past. Recent analysis of the literature and personal work indicates that, during drug treatment of hypertension, a significant decrease in systolic and diastolic blood pressure may be associated with an unchanged pulse pressure, a situation that might contribute to maintaining cardiovascular risk.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Primary aldosteronism (PAL) has been traditionally regarded as a rare cause of hypertension and not worth looking for in the absence of hypokalemia. However, the availability of the aldosterone/renin ratio as a screening test and its application to a wider population of hypertensives has resulted in a marked increase in detection rate, suggesting that PAL is common, with most patients being normokalemic. The spectrum of PAL has been expanded further by the study of familial varieties, in which family screening efforts have permitted the recognition of earlier, sometimes even pre-clinical, stages of disease.Familial hyperaldosteronism type I (FH-I)In FH-I, inheritance of a ‘hybrid’ 11β-hydroxylase/aldosterone synthase gene causes adrenocorticotrophic hormone (ACTH)-regulated aldosterone and ‘hybrid steroid’ (18-hydroxy-cortisol and 18-oxo-cortisol) overproduction. Genetic testing, by Southern blot or polymerase chain reaction-based techniques, has greatly facilitated detection, being more convenient and more reliable than dexamethasone suppression testing, and has led to a fuller appreciation of the marked phenotypic variability in this disorder. The demonstration of excessive, abnormally regulated aldosterone production in normotensive subjects with FH-I suggests that absence of hypertension in such individuals cannot merely be attributed to lack of expression of the hybrid gene. Determinants of hypertension severity may include patient gender, gender of affected parent, degree of hybrid gene expression, and interactions with other genetic and environmental factors. Detailed biochemical studies, including analyses of aldosterone/PRA/cortisol ‘day-curve’ levels, have led to a fuller understanding of aldosterone regulation both before and in response to glucocorticoid treatment in this condition, and prompted a re-examination of current approaches to treatment. Unless ACTH is completely suppressed by glucocorticoid treatment, the hybrid gene dominates over the wild-type aldosterone synthase genes in terms of aldosterone production, both in untreated and treated FH-I. This may in part be due to an abnormality affecting the functional expression of the ‘wild-type’ genes. Demonstration of persisting hybrid gene expression in patients rendered normotensive by very low doses of glucocorticoids suggests that currently recommended doses, aimed at normalizing aldosterone regulation (rather than blood pressure), may be too high, and may therefore place patients at unnecessary risk of developing Cushingoid side effects.Familial hyperaldosteronism type II (FH-II)Like FH-I, FH-II is associated with hyperaldosteronism and probable autosomal dominant inheritance. Unlike FH-I, hyperaldosteronism in FH-II is not dexamethasone suppressible, and is not associated with the hybrid gene mutation. Detection of adrenal mass lesions, which are frequently (17 of 57 patients in the Greenslopes Hospital series) responsible for PAL in FH-II, does not help to differentiate FH-II from FH-I, since mass lesions may also be common in that condition (detected in seven of 21 patients). Biochemically and morphologically, FH-II is indistinguishable from apparently non-familial PAL, and demonstrates similar variability even among individuals of the same family. In one informative family available for linkage analysis, FH-II does not segregate with either the AT1 gene or the CYP11B2 gene, or any other genetic defect in the chromosome 8q21-8qtel region. A genomewide search is in progress. As has already occurred in FH-I, the elucidation of underlying genetic mutations in FH-II is likely to facilitate early detection, thereby helping to broaden its spectrum and to permit close follow-up and appropriately timed institution of specific therapy, and wider detection among patients with hypertension of potentially curable or specifically treatable forms.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Attention is growing for a potential role of magnesium in the pathoetiology of cardiovascular disease. Magnesium modulates mechanical, electrical and structural functions of cardiac and vascular cells, and small changes in extracellular magnesium levels and/or intracellular free magnesium concentration may have significant effects on cardiac excitability and on vascular tone, contractility and reactivity. Thus, magnesium may be important in the physiological regulation of blood pressure whereas alterations in cellular magnesium metabolism could contribute to the pathogenesis of blood pressure elevation. Although most epidemiological and experimental studies support a pathological role for magnesium in the etiology and development of hypertension, data from clinical studies have been less convincing. Furthermore, the therapeutic value of magnesium in the management of essential hypertension is unclear. The present review discusses the molecular, biochemical, physiological and pharmacological roles of magnesium in the regulation of vascular function and blood pressure and introduces novel concepts relating to magnesium as a second messenger in intracellular signaling in cardiovascular cells. In addition, alterations in magnesium regulation in experimental and clinical hypertension and the potential antihypertensive therapeutic effects of magnesium are addressed.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTracking of blood pressure begins in childhood but the relationship between casual blood pressure in childhood and adult levels is not strong enough to predict adult hypertension. The variability of blood pressure in children might suggest that 24 recordings would have less consistency than casual readings when repeated even a relatively short time later. This study compares the shortterm tracking ability of casual versus 24-h blood pressure.DesignAn ambulatory blood pressure device was placed on 50 teenagers. Readings were taken at rest and the device was then worn for approximately 24 h, which included the schoolday. The protocol was repeated 1 year later.ResultsThe correlation coefficient for systolic readings taken 1 year later were: 0.4 for casual, 0.6 for school, 0.6 for home, 0.5 for night-time and 0.8 for 24-h mean systolic blood pressures. When divided into upper and lower tertiles of systolic blood pressure the relationship between tertile ranking 1 year later was stronger for 24-h blood pressure than the casual readings. Casual diastolic pressure was more consistent than the 24-h mean diastolic measurement.ConclusionsIn adolescents, in whom tracking of casual blood pressure has been shown to be poor, 24-h mean systolic blood pressure tracks better than any other time period and significantly better than the casual systolic readings. This study needs to be extended and the ability of 24-h blood pressure to track from childhood to adult life investigated.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo examine the interaction of sodium intake with genetic variations of the angiotensinogen gene and hypertension.DesignA community-based case-reference study.SettingTwo rural Japanese communities.ParticipantsNon-overweight and non-drinking Japanese men and women: 229 hypertensives and 229 age-, sex- and community-matched normotensives aged 32 to 83 years.MethodsPolymorphisms of the angiotensinogen gene detected by an allele-specific polymerase chain reaction. A priori hypothesis is individuals with 174M (threonine-to-methionine substitution) or 235T (methionine-to-threonine substitution) allelic variations may have an elevated risk of hypertension when they have a high sodium intake, estimated by 24-h urine collection and a dietary questionnaire.ResultsThe genotypic frequency of the haplotype including both the 174M and 235T alleles was higher among hypertensives than among normotensives (23 versus 14%,P= 0.02). The frequency of the 174M allele was specifically higher among hypertensives than normotensives (12 versus 7%,P= 0.01), and the odds ratio of hypertension associated with the 174M (versus 174T) allele was 1.8 [95% confidence interval (CI) 1.1–3.0,P= 0.01]. The frequency of the 235T allele did not vary between the two groups (80 versus 82%,P= 0.40). The relationship between the 174M allele and hypertension was more evident among persons who had higher urinary sodium excretion (> = 166 mmol/day) than those with lower excretion (< 166 mmol/day): odds ratio 2.5 (95% CI, 1.2–5.2),P= 0.01 versus 1.5 (95% CI, 0.7–3.1),P= 0.31;Pfor interaction = 0.04, and this trend was primarily observed for early-onset hypertension (< 55 years at onset). A similar but nonsignificant association was observed when stratified using present and past sodium intake scores derived from questionnaires.ConclusionAngiotensinogen genotype may affect the development of early-onset hypertension among Japanese, particularly in those who have a high sodium intake.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo investigate the relationship between inflammatory processes and atherosclerosis in uraemic patients on chronic dialysis.DesignA cross-sectional study in 138 dialysis patients (92 on haemodialysis and 46 on continuous ambulatory peritoneal dialysis).MethodsSerum C-reactive protein (CRP), IgG anti-Chlamydia pneumoniaeantibodies, lipoprotein (a), fibrinogen and plasma homocysteine as well as the intima–media thickness and the number of atherosclerotic plaques of the carotid arteries (by Echo-Colour-Doppler) were measured in each patient.ResultsOne hundred and eight patients had at least one plaque and 26 had more than six plaques. Serum CRP was above the upper limit of the normal range (5 mg/l) in 85 of 138 patients (62%). IgG anti-Chlamydia pneumoniaeantibodies were detectable in 64% of patients (high level in 24%, intermediate in 33% and low in 7%) and undetectable in the remaining 36% of patients. In a multiple regression model age (β = 0.35), serum CRP (β = 0.23), plasma homocysteine (β = 0.19), duration of dialysis (β = 0.19) and pulse pressure (β = 0.18) were independent predictors of intima–media thickness (R= 0.54,P< 0.0001). Similarly, age (β = 0.33), serum CRP (β = 0.29), plasma homocysteine (β = 0.20) and serum albumin (β = −0.18) were independent correlates of the number of atherosclerotic plaques (R= 0.55,P< 0.0001). Furthermore, in smokers, the interaction serum CRP–IgG anti–Chlamydia pneumoniae antibodies was the stronger independent predictor (β = 0.43,P= 0.0001) of the number of atherosclerotic plaques while no such relationship (P= 0.73) was found in non-smokers.ConclusionsIn patients on chronic dialysis treatment CRP is independently associated to carotid atherosclerosis and appears at least in part to be explained by IgG anti-Chlamydia pneumoniaeantibodies level. These data lend support to the hypothesis that inflammation plays a role in the pathogenesis of atherosclerosis in these patients.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveThe observation of local ‘elementary’ Ca2+release events (Ca2+sparks) through ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR) has changed our understanding of excitation–contraction (EC) coupling in cardiac and smooth muscle. In arterial smooth muscle, Ca2+sparks have been suggested to oppose myogenic vasoconstriction and to influence vasorelaxation by activating co-localized Ca2+activated K+(KCa) channels (STOCs). However, all prior studies on Ca2+sparks have been performed in non-human tissues.MethodsIn order to understand the possible significance of Ca2+sparks to human cardiovascular function, we used high spatial resolution confocal imaging to record Ca2+sparks in freshly-isolated, individual myocytes of human coronary arteries loaded with the Ca2+indicator fluo-3.ResultsLocal SR Ca2+release events recorded in human myocytes were similar to ‘Ca2+sparks’ recorded previously from non-human smooth muscle cells. In human myocytes, the peak [Ca2+]iamplitudes of Ca2+sparks (measured as F/F0) and width at half-maximal amplitude were 2.3 and 2.27 μm, respectively. The duration of Ca2+sparks was 62 ms. Ca2+sparks were completely inhibited by ryanodine (10 μmol/l). Ryanodine-sensitive STOCs could be identified with typical properties of KCachannels activated by Ca2+sparks.ConclusionOur data implies that modern concepts suggesting an essential role of Ca2+spark generation in EC coupling recently derived from non-human muscle are applicable to human cardiovascular tissue. Although the basic properties of Ca2+sparks are similar, our results demonstrate that Ca2+sparks in coronary arteries in humans, have features distinct from non-arterial smooth muscle cells of other species.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveThe purpose of the study was to test the hypothesis that the increased media thickness: lumen diameter (M: L) ratio of spontaneously hypertensive rat (SHR) resistance arteries effects enhanced arterial contractile responses compared with those of Wistar-Kyoto (WKY) rat normotensive controls under pressurized conditionsin vitro.DesignContractile responses to the vasoconstrictor agonists noradrenaline and the thromboxane A2analogue U46619 were assessed in femoral and mesenteric resistance arteries (internal diameters ≈ 150μm) after the development of spontaneous myogenic tone at 100 mmHg and at estimatedin vivopressures.MethodsArterial contractile responses and structure were assessed in an arteriograph. Relaxed arterial structure was determined by light microscopy. Mean arterial pressure was determined subsequent to femoral artery cannulation.ResultsUnder relaxed conditions M: L ratios were significantly greater in SHR arteries at 100 mmHg (P< 0.01) and atin vivopressures (P< 0.01). Myogenic responses were not significantly different between SHR and WKY. Under both pressure conditions the contractile responses of SHR femoral arteries were not significantly different to those of WKY in response to either agonist. SHR mesenteric arteries achieved smaller diameters in response to noradrenaline (P< 0.05) and U46619 (P< 0.05) at 100 mmHg. Atin vivopressures, concentration-response relationships of SHR mesenteric arteries for both agonists were not significantly different compared with those of WKY; however, the maximum percentage reduction of lumen diameter in SHR mesenteric arteries in the presence of noradrenaline was greater than in WKY (P< 0.05).ConclusionThe increased M: L ratio of SHR femoral resistance arteries does not impart an exaggerated contractile function in myogenically active resistance arteriesin vitro. For mesenteric arteries the relationship is less clear because increased M: L ratio is associated with increased contractile responses under some, but not all, circumstances.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

BackgroundUncoupling proteins (UCPs) are the inner mitochondrial membrane-associated proteins, which dissipate the proton gradient and generate heat instead of ATP. The involvement of UCPs in energy expenditure and glucose metabolism has been suggested. Recently, we succeeded in cloning of rat UCP2 and UCP3.ObjectiveThe aim of this study was to elucidate the pathophysiological role of UCP2 and UCP3 in hypertension associated with hyperglycemia in stroke-prone spontaneously hypertensive rats (SHR-SP).MethodsUCP2 and UCP3 mRNA levels of cardiac and gastrocnemius muscles in SHR-SP and Wistar–Kyoto (WKY) rats were determined at 6 weeks (prehypertensive stage) and at 15 weeks (hypertensive stage).ResultsUCP2 and UCP3 mRNA levels in the heart of SHR-SP at 6 weeks were significantly higher than those of WKY rats (1.6-fold, 3.6-fold, respectively). These tendencies did not change in the heart at 15 weeks. UCP2 and UCP3 mRNA levels in the skeletal muscle of SHR-SP at 6 weeks were significantly higher than those of WKY rats (1.4-fold, 2.4-fold, respectively). In contrast, at 15 weeks, UCP2 and UCP3 mRNA levels in the skeletal muscle of SHR-SP were significantly lower than those of WKY rats (70 and 36% of WKY rats, respectively). Therefore, the decrease of UCP2 and UCP3 in the skeletal muscle was observed with the concomitant development of hypertension in SHR-SP. UCP2 mRNA levels in the epididymal fat of SHR-SP at 15 weeks were similar to that of WKY rats.ConclusionsAltered gene expression of UCP2 and UCP3 might be related to some pathophysiological aspects in hypertension and glucose metabolism in SHR-SP.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveChronic feeding of a purified synthetic diet induces renin–angiotensin system-dependent moderate high blood pressure in normal Sprague–Dawley rats. The present study was designed to characterize the angiotensin II (Ang II) receptor type 2 (AT2)-specific mechanism of blood pressure regulation in these rats.MethodsThe effect of the AT2receptor antagonist PD123319 (PD) on blood pressure was examinedin vivoin synthetic diet-fed rats. Ang II-dependent contraction of aortic rings prepared from the synthetic diet-fed rats was also investigated.ResultsAfter 8 weeks of feeding the synthetic diet, the mean arterial pressure (MAP) was significantly elevated above levels measured in control rats (117 ± 2 versus 102 ± 3 mmHg,P< 0.05). Intravenous administration of PD to conscious hypertensive rats elicited an immediate dose-dependent increase in MAP that was sustained for approximately 7.4 min with 3 mg/kg PD. The angiotensin converting enzyme inhibitor captopril, but not the Ang II type 1 receptor blocker losartan, significantly attenuated the effect of PD on blood pressure. PD did not increase the plasma level of catecholamines. The PD-dependent blood pressure increase was not observed in normotensive control rats. Aortic ring assays revealed that functional activation of the AT2receptor occurs only in the hypertensive rats, and this AT2response is abolished by indomethacin (5 μmol/l) but not by Nω-nitro-L-arginine methyl ester (100 μmol/l).ConclusionThese results clearly demonstrate that AT2receptor-mediated blood pressure regulation is functional in this experimental model of hypertension. Furthermore, cyclooxygenase metabolites might be the key mediators for the AT2receptor-mediated blood pressure-lowering action.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID