摘要:

This brief review discusses the ways, if and when available, to examine endothelium-dependent changes in diameter in human blood vessels. It stresses the problems in ensuring proper matching between arteries (and veins) from different human sources. It briefly considers the evidencein vitrosupporting the role of endothelium-derived nitric oxide, hyperpolarizing factor(s) and contracting factors (including metabolites of arachidonic acid and endothelin). It emphasizes the difficulty in extrapolating observations obtained in isolated arteries (and veins) to the intact human circulation. The overall conclusion is that the interpretations derived from animal work apply to the human vasculature.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectivesThe aim of this study was to determine whether pulse pressure is a risk factor for coronary artery disease using data from the MRC trial of treatment of mild hypertension, and whether the effect of anti-hypertensive drug therapy on pulse pressure may be a determinant of outcome in treated patients.MethodsLogistic regression and Cox regression analyses were used to compare systolic and diastolic blood pressure, pulse pressure and mean blood pressure as predictors of coronary events and stroke in the MRC Mild Hypertension Trial. The effects of anti-hypertensive drug treatment with bendrofluazide and propranolol on pulse pressure were assessed using 1-year follow-up data. Event rates in the placebo-treated group and responses to anti-hypertensive treatment were measured in quartiles of age-adjusted entry pulse pressure. A ‘four-corners’ analysis was performed, with subjects divided into the upper and lower halves of the distributions of systolic and diastolic blood pressure at entry.ResultsPulse pressure was a stronger predictor of coronary events than systolic, diastolic or mean blood pressure in males by logistic regression. Pulse pressure was similar to systolic pressure as a coronary event predictor on Cox regression. Stroke was predicted most strongly by mean blood pressure. Fatal and non-fatal coronary event rates increased progressively in ascending quartiles of age-adjusted pulse pressure, but there was also a strong correlation with systolic blood pressure. The values of partial logistic regression coefficients in models containing both systolic and diastolic blood pressure also supported a role for pulse pressure in predicting coronary events and for mean blood pressure in predicting stroke. Coronary risk, but not stroke, was inversely related to diastolic blood pressure in the four-corners analysis. In a Cox model, regressions of coronary event probability on systolic blood pressure at entry were significantly and inversely related to diastolic blood pressure categorized in quartiles. Bendrofluazide but not propranolol decreased pulse pressure significantly and was associated with a reduction in cardiovascular events overall, but no definite relationship between the effect of drugs on pulse pressure and specific responses to treatment was seen.ConclusionPulse pressure is a strong risk factor for coronary events in untreated hypertensive male subjects in the MRC Mild Hypertension Trial, whereas stroke is best predicted by mean blood pressure. Bendrofluazide and propranolol have different effects on pulse pressure which may be related to their relative efficacy in the treatment of hypertension, but this possibility requires further study in more suitable populations.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveRecent studies have shown that high resting end tidal CO2(PECO2) is a marker for blood pressure sensitivity to high sodium intake by normotensive humans. The present study investigated the association of restingPECO2with resting blood pressure in participants in the Baltimore Longitudinal Study on Aging (BLSA).DesignPECO2of 314 healthy participants (153 men and 161 women, aged 21–79 years) was measured by a respiratory gas monitor during 25 min of seated rest, and blood pressure every 5 min by an automated oscillometric system. The independent associations ofPECO2and other variables with systolic (SBP) and diastolic (DBP) blood pressure were analysed via multiple regression. Sex differences in age-associated changes inPECO2and in the role of pulmonary capacity in thePECO2-blood pressure relationships were also studied.ResultsRestingPECO2was an independent predictor of SBP in women (β=0.215;P< 0.0015; overallr2= 0.27;P< 0.0001), and accounted for more than 10% of the variance in SBP in women over age 50 years. No such associations ofPECO2with SBP of men, or with DBP of men or women, were observed.PECO2was lower in younger women (36.0 ± 0.9 mmHg) than in younger men (40.4 ± 2.0), but higher in older women (37.1 ± 0.5) than in older men (35.5 ± 0.4).ConclusionsPECO2is an independent determinant of resting SBP in women, especially those aged 50 years or more. The origin of individual differences in restingPECO2and its possible role in the development of chronic hypertension remain to be clarified.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo determine the qualitative and quantitative expression of alpha and gamma sodium pump subunits in whole kidney and nephron segment RNA from Sprague Dawley rats, spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats.DesignA novel reverse transcription polymerase chain reaction technique was devised which provides accurate and precise measurement of the number of molecules of specific transcript abundance, a measurement of gene expression. This allows the quantitative comparison of multiple samples across multiple subjects and, since the estimates are accurate rather than relative, can also be used to make quantitative comparisons across expressed genes, such as isoforms and subunits of the heterotrimeric renal sodium pump.MethodsWe examined which catalytic isoforms were expressed and then quantified transcript abundance in whole kidney and convoluted and straight segments of the proximal tubule.ResultsAlpha 1 and gamma transcripts, but not alpha 2, alpha 3 or alpha 4 isoforms, were consistently observed in nephron segments. Levels of alpha 1 were lower in kidney RNA from 15–16-week-old SHR than in WKY rats of the same age (P= 0.001), but were not different between SHR and WKY in 4–5-week-old animals. No significant difference was observed in gamma subunit abundance in kidney RNA from 4±5-week-old animals; however, at 15–16 weeks, the expression in SHR was one-third that in WKY rats (P= 0.003). In proximal convoluted tubules from 4–5-week-old animals, the level of alpha 1 RNA expression was lower (P= 0.03) in SHR than in WKY rats. In addition, levels of alpha 1 in proximal straight tubule from the 4–5-week-old SHR were also lower than in WKY rats (P= 0.02). This difference was even greater in 15–16-week-old animals: in SHR, alpha 1 expression was less than 20% of the level of expression in WKY rats (P= 0.0003). Expression of the gamma subunit exhibited a similar pattern of downregulation in SHR. In RNA from proximal convoluted tubules and proximal straight tubules from both 4–5- and 15–16-week-old animals, expression of the gamma subunit was demonstrated to be significantly lower in SHR than in WKY rats.ConclusionThe results indicate a coordinate reduction in the abundance of sodium pump alpha and gamma subunits in the proximal tubules of SHR, which occurs early during the development of hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

BackgroundAn isoenzyme of 11β-hydroxysteroid dehydrogenase (11β-HSD), 11β-HSD-2 confers aldosterone specificity on the mineralocorticoid receptor (MR) and is found collocated in renal cortical collecting duct cells with the MR. To investigate whether the salt sensitivity of the Dahl salt-sensitive (S) rat is due to 11β-HSD deficiency, we measured 11β-HSD-1 and 11β-HSD-2 mRNA levels in the kidneys of Dahl-S and Dahl salt-resistant (R) rats. In addition, we studied the effects of gender, age and dietary sodium on expression of mRNA for the two isoforms. S and R rats were placed on low- or high-sodium (HNa) diets and sacrificed after 33 and 115 days. Rat kidney RNA was isolated and 11β-HSD-1 and 11β-HSD-2 mRNA levels were measured on Northern filter hybridization using isoform-specific probes.ResultsNo strain differences were observed in the mRNA expression of the two isoforms of 11β-HSD under any of the experimental conditions. No gender or age differences were observed in 11β-HSD-2 mRNA but HNa diet almost doubled 11β-HSD-2 mRNA (P< 0.0009). 11β-HSD-1 mRNA levels were consistently higher, more than double, in male rats versus females rats (P< 0.0001), and in the 115-day-old rats versus the 33-day-old rats (P< 0.0001). Dietary sodium intake did not affect 11β-HSD-1 mRNA levels.ConclusionsThere is no difference in the expression of the two isoforms of 11β-HSD in the kidneys of the S and R rats, which might explain the salt sensitivity and higher blood pressure of the S rat. Renal 11β-HSD-1 mRNA levels are higher in male than in female rats, and in the older rats of both strains. In the kidney, the 11β-HSD-2 gene is regulated by sodium status but is not affected by gender or age.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe 825T allele of the G protein β3 subunit is associated with hypertension in Caucasians. To generate a novel hypothesis regarding the underlying mechanisms, we examined for a potential association of the 825T allele with obesity in hypertension.Patients and methodsWe genotyped 197 hypertensive individuals (104 men, 93 women; mean age 54 years) recruited from the general population in the Heidelberg (Germany) area. Data acquisition included age at first diagnosis of hypertension, body weight and height, actual treated blood pressure values, and history of stroke and/or myocardial infarction (cardiovascular events).ResultsThe 825T allele was significantly (P= 0.02) associated with body mass index (BMI), mean values being 28.6 ± 4.1, 27.0 ± 3.1, and 26.1 ± 3.8 kg/m2for TT, TC, and CC respectively, which persisted after correction for sex and age. The 825T allele frequency was 23.8, 31.4 and 40.0% in individuals with normal weight (BMI < 24.9 kg/m2), overweight (BMI 25.0–29.9 kg/m2), and obesity (BMI >29.9 kg/m2), respectively. Odds ratio for obesity versus normal weight was 3.9 [95% confidence interval (CI) 1.1–14.3;P= 0.03] for TT/CC and 1.8 (95% CI 0.7–4.6;P= 0.18) for TC/CC. BMI and age, but not genotype were significantly correlated with cardiovascular events as determined by logistic regression analysis.ConclusionsThe findings suggest an association between obesity and the 825T allele, a genetic marker for enhanced G protein reactivity, in hypertensive individuals.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveWe have demonstrated that cultured vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR), but not from normotensive Wistar-Kyoto (WKY) rats, produce angiotensin II (Ang II) in a homogeneous culture with increased levels of angiotensinogen, cathepsin D and angiotensin converting enzyme (ACE) at early passages. In the current study, we investigated how changes in the cell phenotype affect the Ang II-generating system and the growth of VSMC from SHR.Design and methodsWe evaluated basal DNA synthesis by [3H]thymidine incorporation, immunofluorescence of α-smooth muscle (SM) actin, mRNA expression of phenotype markers such as SM22α appeared by contractile phenotype, Ang II-generating system components and growth factors by reverse transcription and polymerase chain reaction analysis, and Ang II levels by radioimmunoassay in quiescent VSMC from WKY/Izumo rats and SHR/Izumo at passages 4, 8 and 12.ResultsBasal DNA synthesis in VSMC from WKY rats increased with increasing passage number, whereas in cells from SHR it was markedly higher at early passages and was not affected by the passages. At early passage numbers, immunofluorescence of α-SM actin was stronger in VSMC from WKY rats than in cells from SHR, but decreased after several passages. Expression of SM22α mRNA was higher in VSMC from WKY rats than in cells from SHR at early passages, and decreased after several passages in cells from both rat strains. Expression of matrix Gla mRNA was higher in VSMC from SHR than in cells from WKY rats at early passage, and increased after several passages in cells from both rat strains. Ang II was not detected at early passages but increased in VSMC from WKY rats with increasing passage, whereas it was detected in VSMC from SHR at early passages and did not change with the passages. Expression of angiotensinogen mRNA was higher in VSMC from SHR than in cells from WKY rats, and was not affected by the passages. Expressions of cathepsin D and ACE mRNA were higher in VSMC from SHR than in cells from WKY rats at early passage, and were increased by the passages in VSMC from WKY rats. Expressions of transforming growth factor-β1, platelet-derived growth factor A-chain, and basic fibroblast growth factor mRNA were significantly higher in VSMC from SHR than in cells from WKY rats, and were increased by the passages.ConclusionThese data indicate that early in culture VSMC from SHR have the synthetic phenotype, whereas VSMC from WKY rats have the contractile phenotype which then changes to the synthetic phenotype after increased passage numbers, with increased expression of cathepsin D and ACE, which produce Ang II, and increased expression of Ang II-related growth factors, which induce the exaggerated growth observed in VSMC from SHR.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo distinguish between static (due to slow changes in pressure) and dynamic (due to pressure pulsatility) components of aortic compliance over a large pressure rangein vivoand to examine the effects of increased vascular mass and smooth muscle tone on these components.MethodsUsing ultrasound wall tracking, aortic lumen area-pressure curves were generated in anaesthetized rats over a broad range of pressures by altering blood volume. The compliance coefficient calculated at each mean pressure was considered the dynamic compliance at that pressure; the slope of the diastolic lumen area-pressure curve represents static compliance. Experiments were performed in control rats and rats treated with angiotensin II (ANG II) acutely (500 ng/kg per min intravenously) to modify vascular tone or chronically (250 ng/kg per min subcutaneously for 2 weeks) to modify vascular mass.ResultsThe dynamic compliance-pressure curve approximated a parabola. Maximal dynamic compliance (0.272 ± 0.026 mm2/kPa in control rats) was achieved at near-normotensive pressure (± 105 mmHg). The diastolic lumen area-pressure curve showed an exponential relationship within a physiological range (30–130 mmHg). ANG II-induced increases in aortic wall mass or smooth muscle tone did not modify the relationship between static or dynamic compliance and pressure.ConclusionsThese findings demonstrate that static and dynamic mechanics of the rat thoracic aorta depend differently on blood pressure. Static compliance increases slightly with pressure in a physiological range, while dynamic compliance is auto-regulated around normotensive pressures. Neither static nor dynamic compliance of the rat thoracic aorta are influenced by ANG II-induced increases in aortic wall mass or smooth muscle tone.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID