摘要:

BackgroundIncreased pulse pressure and arterial stiffness are identified as predictors of cardiovascular risk in older hypertensive populations, particularly that of myocardial infarction. Because increased pulse pressure involves an increase in systolic (SBP) and a decrease in diastolic blood pressure (DBP), and because the former promotes cardiac hypertrophy and the latter alters coronary perfusion, a drug regimen reducing pulse pressure and decreasing arterial stiffness might further reduce cardiovascular risk. Under conventional treatment, normalization of DBP (≤ 90 mmHg) is not consistently associated with normalization of SBP (≤ 140 mmHg).Therapeutic designsIn individuals older than 50 years, the goal of antihypertensive treatment should be, not only to decrease mean blood pressure (to less than 100 mmHg), but also to decrease pulse pressure (to less than 50 mmHg). Using appropriate pharmacological tools, trials should test whether an active decrease in arterial stiffness might produce an attenuation of the age-related increase in SBP and decrease in DBP, thus delaying the age-related increase in pulse pressure and decreasing further cardiovascular risk. This procedure requires concomitant non-invasive evaluations of aortic stiffness.ConclusionThe studies that are required in hypertension should use two different approaches: novel titrations of conventional drugs to achieve a decrease in either SBP or pulse pressure, and development of new drugs acting selectively on the large artery wall, to facilitate the conduct of subsequent controlled trials.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

We postulate that the genetic factor increasing the propensity of black people of sub-Saharan African descent to develop high blood pressure is the relatively high activity of creatine kinase, predominantly in vascular and cardiac muscle tissue. Such greater activity of creatine kinase has been reported in skeletal muscle of black untrained subjects has been reported to be almost twice the activity found in white subjects. Creatine kinase, a key enzyme of cellular energy metabolism, increases the capacity of the cell to function under high demands. The enzyme regulates, buffers and transports, via phosphocreatine and creatine, energy produced by glycolysis and oxidative phosphorylation to sites of energy consumption such as myofibrils and membrane ion pumps. At these cellular locations, it is involved in the contraction process and active trans-membranous transport by readily providing the ATP needed for these processes. In addition, creatine kinase is increasingly reported to be involved in trophic responses. Furthermore, by using H+and ADP to synthesize ATP, creatine kinase prevents acidification of the cell, providing relative protection against the effects of ischaemia. Greater creatine kinase activity in cardiovascular muscle and other tissues with high energy demands could increase cardiovascular contractile reserve, enhance trophic responses and increase renal tubular ability to retain salt. This could facilitate the development of arterial hypertension under chronic provocative circumstances, with higher mean blood pressures, more left ventricular hypertrophy and relatively fewer ischaemic events. Therefore, greater cellular activity of creatine kinase might explain the greater hypertension risk and the clinical characteristics of hypertensive disease observed in the black population.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The renin–angiotensin–aldosterone system actively participates in the derangement of renal function since the early stages of heart failure (HF). A diminished capacity to excrete sodium secondary to increased proximal tubular re-absorption and loss of the renal functional reserve are the two most relevant initial alterations of renal function in which angiotensin II has been proven to act directly. Meanwhile, the octapeptide contributes to maintain glomerular filtration rate (GFR) within normal limits through efferent arteriole vasoconstriction. Administration of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor antagonists (ARA) may thus be accompanied by a functional fall in that parameter. Advanced age, higher initial serum creatinine, history of hypertension, diabetes and atrial fibrillation predict the onset of GFR impairment associated with blockade of the renin–angiotensin system. Concomitant administration of betablockers may help to protect renal function, and preliminary data indicate that the combination of ACEi and ARA is not accompanied by a higher renal risk. The good prognostic effects of aldosterone antagonists in HF does not seem to be related to intrarenal effects of these compounds with the exception of preventing potassium loss and hypokalemia. The systematic therapeutic use of drug(s) provided with beneficial renal effects, to treat arterial hypertension or myocardial ischemia, may contribute to delay of, or prevent the development of HF.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveThis study was aimed to evaluate the determinants of elevated blood pressure (BP) in adolescents.Design and methodsWe retrospectively evaluated the BP and anthropometric data in 419 Japanese students (268 males and 151 females) during high school and university. Their annual health records were analysed for BP, heart rate, height and body weight between the ages of 15 and 21 years.ResultsThe number of hypertensive students did not vary significantly during the 6 years. Concerning changes in BP categories according to the modified JNCVI classification between the ages of 15 to 21 years, 150 males kept a normal BP (keeping normal BP group); 39 males developed high BP (developing high BP group); 37 males kept high BP (keeping high BP group); and 42 males became normal BP (becoming normal BP group). The majority of females (n= 144, 95.4%) were included in the keeping normal BP group. In male students, both the keeping and becoming normal BP groups, especially the latter, showed a significant decrease in heart rate over the 6 years, while the other two groups showed no change. The height and body weight of each of the four groups showed a significant increase, but the body mass index (BMI) of the males in the becoming normal BP group did not increase over the 6 years. Body weight and BMI at the age of 15 years in the male keeping normal BP group were significantly below that of the other three groups; this difference persisted at the age of 21 years. Furthermore, male university students who showed a BP above ‘high–normal’ at the age of 21 years exhibited a significantly higher BP, heart rate, body weight and BMI than did the normotensives, when they were high school students. Stepwise regression analysis of the data showed that the best predictors of BP at the age of 21 years were the initial high school BP and BMI levels and changes in BMI and heart rate during the 6-year period for male students.ConclusionResults indicate that the BP and BMI during high school and the changes in BMI and heart rate from high school to university influenced the BP at the age of 21 years in male students. Data indicate that information on the prevention and management of hypertension including weight control should begin early, especially in male adolescents.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveTo investigate mechanisms underlying the training-induced blood pressure-lowering effect we analyzed the hemodynamic responses and morphometric changes of the skeletal muscle microcirculation of spontaneously hypertensive (SHR) and normotensive Wistar–Kyoto (WKY) rats during an exercise training program.DesignTraining (50–60% VO2 max) was performed on a treadmill for 13 weeks and control groups were kept sedentary over the same period of time. Trained and sedentary rats were chronically instrumented for hindlimb flow and arterial pressure (AP) recordings under conscious unrestrained conditions. Gracilis and myocardial muscle samples were obtained for morphometric analysis after transcardiac perfusion of fixative.ResultsSHR, when compared to WKY presented an elevated blood pressure, an increased relative hindlimb vascular resistance, capillary rarefaction in both gracilis and myocardium and an increased wall-to-lumen ratio of gracilis arterioles. Training increased significantly both capillary density and capillary/fiber ratio in the gracilis and myocardium of WKY and SHR groups, causing a complete reversal of capillary rarefaction in trained SHR. In SHR, training also reduced resting blood pressure and caused normalization of both relative hindlimb vascular resistance and gracilis arterioles wall-to-lumen ratio. Regression analysis revealed strong positive correlation between hindlimb vascular resistance and mean AP (MAP) and between arterioles wall-to-lumen ratio and MAP.ConclusionsThe results suggest that low-intensity training can significantly reduce pressure in SHR while normalizing both the arteriole morphology and the resistance of the skeletal muscle microcirculation.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesThe physiological effects of polymorphisms of the renin–angiotensin—aldosterone system (RAAS) are poorly understood. Long-term effects of genetic variants can be studied in cross-sectional linkage studies. In this study, we examined the short-term effects of genetic polymorphisms of the angiotensin II AT1-and AT2-receptor subtypes in humans by means of angiotensin II infusion.MethodsIn 120 male, white, young (26 6 3 years) subjects with normal or mildly elevated blood pressure, changes in mean arterial blood pressure, aldosterone levels, glomerular filtration rate (GFR), and renal plasma flow (RPF) were measured in response to angiotensin II infusion (0.5 ng/kg per min and 3.0 ng/kg per min, each over 30 min). The −22228 G/A polymorphism of the AT1-receptor gene, and the +1675 G/A polymorphism of the AT2-receptor gene were determined by restriction digestion and single strand conformation polymorphism analysis, respectively.ResultsInfusion of angiotensin II resulted in an increase in mean arterial pressure, serum aldosterone levels and GFR, and in a decrease in RPF (allP< 0.001). However, at similar baseline mean arterial pressure, aldosterone levels, and renal haemodynamics, the response to angiotensin II did not significantly differ across the AT1-and AT2-receptor genotypes with the sample size of our study being adequate to detect relevant differences accross the genotypes with a power of > 90% for all parameters.ConclusionsThe response to angiotensin II infusion does not differ across the the AT1-and AT2-receptor genotypes examined in our study. However, long-term effects of variants of angiotensin II receptor genes cannot be ruled out with this approach.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo review, on a genome-wide scale, a linkage result obtained in an earlier candidate gene analysis in this same study sample, and to look for other possible contributing genetic loci predisposing to hypertension in this population.DesignAn affected sibpair linkage study with highly polymorphic genetic markers spanning the genome at an average intermarker density of 10 cM.ParticipantsA total of 47 families with two affected siblings (mostly dizygotic twins) and all available additional family members from the genetic isolate of Finland. The families were identified through the Finnish Twin Cohort Study, the total number of this follow-up cohort being 13 888. The study sample was selected on the basis of early-onset hypertension with minimal presence of other phenotypic risk factors such as obesity.ResultsThe AT1locus stood out as the most significant locus in this population (maximum likelihood score 4.04). Some evidence for linkage was also detected with markers on chromosomes 2q (maximum likelihood score 2.96), 22q (2.07), and Xp (2.41).ConclusionsOur results establish the role of the AT1locus, on a genome-wide scale, as a major contributing locus to essential hypertension in this study sample.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectivesTo test the effects of chronic angiotensin II administration on blood pressure and small artery biomechanics in the female sex hormone-depleted state (proposed to increase cardiovascular vulnerability) and with hormone replacement.DesignBiomechanical properties of saphenous artery segments from ovariectomized (n= 10), ovariectomized + chronically angiotensin II infused-(n= 10), and ovariectomized + chronically angiotensin II-infused + sex hormone-replaced (n= 10) rats were studied.MethodsSurgical ovariectomy was performed. Osmotic minipumps were used for chronic angiotensin II infusion (100 ng/min per kg). For hormone replacement therapy, oestradiol-propionate, 450 μg/kg for 7 days + medroxyprogesterone-acetate, 15 mg/kg for 14 days were given, intramuscularly. After 4 weeks, cylindrical segments of the saphenous artery were prepared and subjected to in-vitro microarteriographic measurements. Pressure – diameter curves (0–200 mmHg) were recorded in Krebs–Ringer solution, with smooth muscle contracted (norepinephrine, 16 μmol/l) and with relaxed (papaverine, 28 μmol/l).ResultsChronic angiotensin II infusion significantly reduced the inner radius (at 100 mmHg: 298 ± 17 μm versus 347 ± 7 μm,P< 0.001), while wall-thickness did not change. Hormone replacement restored the morphological radius (333 ± 7 μm). Angiotensin II infusion slightly increased the full contraction range of the segments (defined as the percentage difference between fully contracted and fully relaxed diameters), which was further significantly increased by hormone replacement (39 ± 4%, 46 ± 8%, 62 ± 7% at 100 mmHg, in the three groups, respectively;P< 0.05). Despite unaltered stiffness in relaxed state, elastic moduli computed for the contracted segments decreased after hormone replacement.ConclusionsThese observations give further experimental support to the hypothesis that sex hormone replacement might be useful in preventing the development and/or stabilization of postmenopausal hypertension, as well as in treating existing disease.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

ObjectiveIf calcium channel blockers affect nitric oxide synthesis in the vascular tissue, they could influence disease progression in coronary arteries. We investigated the effects of the calcium channel blocker amlodipine on nitric oxide synthesis by measuring the production of nitrite, a stable metabolite of nitric oxide, in vascular smooth muscle cells.MethodsWe measured the production of nitrate in cultured rat vascular smooth muscle cells with the Griess reagent. Inducible nitric oxide synthase protein and mRNA expression were assayed by Western blotting and reverse transcription-polymerase chain reaction, respectively. The levels of NF-κB proteins in nuclear extracts were analyzed by gel retardation assay.ResultsIncubation of cultures with interleukin-1β (10 ng/ml) for 24 h caused a significant increase in nitrite generation. Interleukin-1β-induced nitrite production by vascular smooth muscle cells was significantly increased by amlodipine in a dose-dependent manner. This augmentative effect of amlodipine was completely abolished in the presence of NG-monomethyl-L-arginine or actinomycin D. Amlodipine-induced nitrite production was accompanied by increased inducible nitric oxide synthase mRNA and protein accumulation. Interleukin-1β induced NF-κB activation in vascular smooth muscle cells, and addition of amlodipine further increased this NF-κB activation. The effect of amlodipine on nitrite production was maintained in the presence of the calcium channel agonist Bay K 8644.ConclusionAmlodipine enhances nitric oxide synthesis in cytokine-stimulated cultured vascular smooth muscle cells by L-type calcium channel-independent mechanisms.

ISSN:0263-6352    

出版商:OVID    

年代:2000

数据来源: OVID