ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo study whether the SAgene locus (on rat chromosome 1) and the sodium potassium ATPase α1gene locus (on rat chromosome 2) contribute to the elevated blood pressure in the Milan hypertensive rat.DesignCo-segregation analysis using polymorphisms in the SAand Na+/K+-ATPase α1genes in F2rats from a cross of Milan hypertensive and Milan normotensive rats. Analysis of SAand N+/K+ATPase α1gene expression in kidneys of 6 and 25 weeks old Milan hypertensive and normotensive rats.MethodsGenotyping of F2rat DNA by restriction digestion and Southern blotting and comparison of messenger RNA levels by northern blot analysis.ResultsRenal expression of SAwas considerably higher in normotensive than it was in hypertensive rats aged 6 and 25 weeks. Despite this difference the SAgenotype did not co-segregate with blood pressure, although the Milan hypertensive rat allele did co-segregate with greater body weight (P= 0.0014) for male F2rats. Expression of Na+/K−-ATPase α1was higher in the kidneys of young hypertensive rats than it was in those of normotensive rats and did not decline with age as occurred in the normotensive rats. However, again the Na+/K++ATPase α1genotype did not co-segregate with blood pressure.ConclusionsDespite differences in the patterns of expression of SAand Na+/K+-ATPase α1 genes in the kidneys of Milan hypertensive and normotensive rats, we found no evidence of co-segregation of either gene with blood pressure. Our results suggest that either SAis simply acting as marker for a linked gene in other crosses for which co-segregation with blood pressure has been observed, or at least, the level of its renal expression is not the sole determinant of its effect on blood pressure. The failure of the Na+/K+-ATPase α1gene to co-segregate with blood pressure suggests that its greater expression in the kidney of the Milan hypertensive rat is either reactive or controlled by other genetic loci.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundThe catalytic α and smaller β subunits of the plasma membrane Na,K-ATPase occur in various molecular forms (α1, α2, α3, β1and β2). The α isoforms of the enzyme have varying affinities for ouabain and exist in different tissues with particular distribution patterns.ObjectiveTo document the existence of isoforms of the Na,K-ATPase in cultured human umbilical vein endothelial cells.MethodsMicrosomal fractions were prepared by differential ultracentrifugation from primary cultures of human umbilical vein endothelial cells and from such cells obtained after three passages. Na,K-ATPase activity was assayed using the coupled assay method and sensitivity to ouabain was determined in the presence of varying concentrations of ouabain. Specific antibodies for the various Na,K-ATPase isoforms were used to label these different proteins by immunocytochemistry in endothelial cells and by Western blotting in isolated membranes.ResultsIn plotting the dose–response curves for Na,KATPase activity in response to ouabain we assumed the existence of two independent sites exhibiting different affinities for ouabain (in the μmol/l and the nmol/l ranges). The contribution of low-affinity sites was threefold that of high-affinity sites. After three passages in culture, a specific increase in Na,K-ATPase activity of the high-affinity sites was observed compared with that of cells from primary cultures. Confocal microscopy revealed the existence of β1, β2, and α1subunit proteins in human umbilical endothelial cells. Staining for α3isoform was less pronounced and no obvious α2was detected.ConclusionThese findings suggest that human umbilical vein endothelial cells contain β1, β2, a large amount of α1isoform with an apparently low affinity for ouabain, and a lesser amount of high-affinity sites, which may correspond to the α3protein.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundWe have previously shown that a locus on rat chromosome 5, termed STR 2, co-localizes with the genes encoding atrial natriuretic and brain natriuretic peptides, and is closely linked to the development of strokes in rats of a F2hybrid cohort obtained by crossing stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats. We also demonstrated that there are significant differences in vascular functioning that are co-segregated with stroke latency of stroke-prone spontaneously hypertensive rats.ObjectiveTo investigate the vascular responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats.Design and methodsIn view of the important vasoactive properties of natriuretic peptides, we tested the vascular responses to 10−11–10−9mol/l atrial natriuretic peptide and to 10−11–10−7mol/l brain natriuretic peptide in isolated rings of aortas and internal carotid arteries obtained from stroke-prone and stroke-resistant spontaneously hypertensive rats. The 6-week-old rats were exposed for 4 weeks either to their regular diet (n = 15 of both strains) or to the stroke-permissive Japanese-style diet (n = 14 of both strains). A group of 14 normotensive, age-matched and sex-matched Wistar–Kyoto rats was also studied.ResultsSystolic blood pressures in stroke-prone and stroke-resistant spontaneously hypertensive rats were similar, and were significantly higher than those in Wistar–Kyoto rats. Vascular responses to nitroglycerin, atrial natriuretic peptide, and brain natriuretic peptide in rats of the two hypertensive strains and in Wistar–Kyoto rats fed their regular diet were comparable. In contrast, the vasorelaxant responses to atrial natriuretic peptide in stroke-prone spontaneously hypertensive rats fed Japanese diet were lower both in aortas and in internal carotid arteries than were those in spontaneously hypertensive rats (bothP< 0.05 by analysis of variance) and in Wistar–Kyoto rats (bothP< 0.05). Similarly, vasorelaxant responses to brain natriuretic peptide were lower both in aortas and in internal carotid arteries of stroke-prone spontaneously hypertensive rats than they were in spontaneously hypertensive rats (bothP< 0.05) and in Wistar–Kyoto rats (P< 0.05). The responses to nitroglycerin in the stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats fed Japanese-style diet were also similar.ConclusionThe vasorelaxant effects of natriuretic peptides are impaired in stroke-prone spontaneously hypertensive rats. This abnormality could play a role in the pathogenesis of stroke incidence in this hypertensive model.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundCarotid artery structure change was associated with coronary artery stenosis by angiography of subjects who were for the most part symptomatic.ObjectiveTo determine whether structural changes at multiple extracoronary sites were associated with noninvasively detected coronary calcium for 94 asymptomatic high-risk men.Methods and resultsB-mode ultrasonography allowed us to detect plaque at three sites (carotid, femoral, and abdominal aorta) and to measure intima-medial thickness both in common carotid and in femoral arteries. Ultrafast computed tomography determined the presence and amount of coronary calcification. After adjustment for age, plaques at two or three sites were associated with extensive amounts of coronary calcium [odds ratio 4.94 (95% confidence interval 1.08–23)], but not with the presence of coronary calcium; increase in carotid intima-medial thickness was not associated with presence and extent of coronary calcium; and increase in femoral intima-medial thickness was associated with presence of coronary calcium [odds ratio 1.44 (95% confidence interval 1.03–2)] and extensive coronary calcium [odds ratio 1.50 (95% confidence interval 0.97–2.33)]. Adjustment for cardiovascular risk factors attenuated these associations.ConclusionsFemoral intima–medial thickness predicted presence of coronary calcium whereas femoral intima–medial thickness and overall multiple plaques predicted extensive coronary calcium. Because coronary calcium is a marker of atherosclerosis and a predictor of coronary events, B-mode ultrasonography could be of clinical value for stratifying coronary risk.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo evaluate the effects of patterns of drinking (weekend versus daily drinking) on the pressor responses to alcohol in 55 male drinkers using clinic and 24 h ambulatory blood pressure monitoring.DesignA randomized, controlled cross-over trial.MethodsRecruitment required a regular alcohol intake of 210–500 ml absolute alcohol/week, with > 60% consumed as beer. Fourteen subjects were categorized as predominantly weekend drinkers, whereas the remaining 41 subjects regularly drank on a daily basis. After 4 weeks of familiarization, all subjects were randomly allocated to drinking low-alcohol beer (0.9% vol: vol) only or to maintain their usual drinking habits with provision of full-strength beer (5% vol: vol) for 4 weeks. They then switched back to their usual drinking habits or low-alcohol beer, respectively, for a further 4 weeks while maintaining their usual drinking pattern.ResultsBaseline ambulatory systolic blood pressure in weekend but not in daily drinkers was 2.4 mmHg higher on Monday than it was on Thursday (P= 0.02). This Monday-Thursday difference was lost during intervention. When subjects switched from the high-alcohol to the low-alcohol period the falls in ambulatory systolic blood pressure in weekend (3.1 mmHg,P< 0.001) and daily drinkers (2.2 mmHg,P< 0.001) were similar. Most of the fall was evident during week 1 of the low-alcohol period for weekend drinkers but not until week 4 for daily drinkers.ConclusionThe pressor response to alcohol consumption is similar in magnitude in weekend and daily drinkers, present throughout a 24 h period and has a rapid onset/offset in weekend drinkers but is more sustained in daily drinkers.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

BackgroundA positive association of chronic exposure to alcoholic beverages with blood pressure and the prevalence of hypertension has been described in epidemiological surveys, but the influence of time elapsed since last ingestion in this setting was not demonstrated.DesignA cross-sectional, population-based survey.MethodsIn total 1089 adults from Porto Alegre, randomly selected from a population-based, multi-stage probability sample, were interviewed at home. The average daily alcohol intake of each subject was calculated taking into account the concentration of ethanol in the beverages (distilled or fermented beverages), and the time elapsed between the last ingestion of ethanol and the moment of blood pressure determination. Standardized sitting blood pressure and anthropometric parameters were collected. The magnitude and shape of the associations were analyzed considering blood pressure as a continuous variable and the prevalence of arbitrarily defined hypertension. Simple and multiple linear regression models, including models to identify nonlinear associations, with quadratic and cubic terms of the amount of alcohol consumed, were employed. Blood pressure means were compared by analysis of variance and analysis of covariance. The association between hypertension and exposure to ethanol was analyzed through logistic regression models, controlling for various potential confounders.ResultsPositive nonlinear associations of the amount of alcohol consumed with blood pressure and the prevalence of hypertension (≥160/95 mmHg) were found, independent of age, years of education, smoking, and use of oral contraceptive and antihypertensive drugs. The consumption of 30 g/day ethanol was associated with increases of 1.5 and 2.3 mmHg in diastolic and systolic blood pressures, respectively, for men, and 2.1 and 3.2 mmHg, respectively, for women. The prevalence of hypertension was higher among those ingesting more than 30 g/day (odds ratio = 2.9,P< 0.01). The time elapsed between the last ingestion and blood pressure measurement was independently associated with the prevalence of hypertension. Men with last consumption of alcohol 13–23 h prior to measurement had odds of being hypertensive 2.6 (confidence interval 1.3–5.0) greater than did subjects who had consumed alcoholic beverages 24 h and more before the blood pressure determination. For men, systolic and diastolic blood pressures were lower during the first 3 h after ingestion and increased afterward. Frequency of consumption and type of beverage consumed were not independently associated with level of blood pressure.ConclusionA time-dependent association between alcohol consumption and effects on blood pressure, demonstrated in experimental studies, was found for free-living individuals selected at random.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo investigate the effects of voluntary running exercise from 4–20 weeks of age on aortic compliance in Wistar–Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).DesignFor each species we made comparisons between rats housed with an exercise wheel locked (10 rats) and unlocked (10 rats).MethodsRats were killed using CO2asphyxia and the aorta and heart of each rat were rapidly removed. The heart was dissected and weighed. A 4 mm descending proximal aortic ring was mounted on wires in an organ bath for determination of static compliance from the slope of the diameter–pressure relationship derived using Laplace's equation.ResultsDuring the final 2 weeks of training WKY rats ran an average of 7.9 ± 1.0 km/24 h compared with 1.0 ± 0.2 km/24 h for SHR. Body weights of WKY rats and SHR and of animals housed with locked and unlocked exercise wheels did not differ. The septum, left ventricle and total heart weights and left ventricular: body weight ratios of sedentary SHR were greater than those of sedentary WKY rats. Trained WKY rats had significantly higher atrial, left and right ventricular and total heart weights and left ventricular: body weight ratios than did untrained WKY rats. Aortic compliance was higher in trained than it was in sedentary WKY rats (12.3 ± 0.4 versus 14.2 ± 0.5 μm/mmHg,P< 0.05). There was no difference between heart weights and aortic compliances of SHR housed with exercise wheels locked and unlocked.ConclusionExercise-trained WKY rats had greater intrinsic aortic compliance when it was measured staticallyin vitro, which supports results of previous human work revealing a blood-pressure-independent component in the elevation of arterial compliance with training. The lower physical activity of the SHR strain used in this study could contribute to their higher blood pressures and lack of change in aortic compliance with exercise training.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectivesTo examine hemodynamic variables in corticotropin-induced hypertension in rats and the effects of reversal of the hypertension by L-arginine on the hemodynamic profile.MethodsSixty male Sprague–Dawley rats were randomly divided into four groups: sham treatment (0.9% NaCl, injected subcutaneously); 0.5 mg/kg corticotropin per day, subcutaneously; 0.6% L-arginine in food plus sham; and L-arginine plus corticotropin. Systolic blood pressure, water and food intakes, urine volume, and body weight were measured every second day. After 10 days mean arterial blood pressure was measured by intra-arterial cannulation, and cardiac output, and renal, mesenteric, and hindquarter blood flows were determined using transonic small animal flowmeters.ResultsInjection of corticotropin increased blood pressure, water intake, urine volume, and plasma sodium concentration, and decreased body weight and plasma potassium concentration. It increased cardiac output (P< 0.01), mesenteric blood flow (P< 0.05), and renal vascular resistance (P< 0.05), and decreased renal blood flow (P< 0.05), but did not change calculated total peripheral resistance, hindquarter blood flow, mesenteric or hindquarter vascular resistance. L-arginine prevented corticotropin-induced rises in blood pressure (P< 0.001) and renal vascular resistance (P< 0.05), and a fall in renal blood flow (P< 0.05), but did not affect other hemodynamic variables.ConclusionThe hemodynamic profile of corticotropin-induced hypertension in the rat is characterized by a rise in cardiac output and renal vascular resistance, a fall in renal blood flow, but no change in total peripheral resistance, hindquarter blood flow, mesenteric vascular resistance, or hindquarter vascular resistance. L-arginine prevented corticotropin-induced rises both in blood pressure and in renal vascular resistance in the rat. These data suggest that the increase in renal vascular resistance might play a role in corticotropin-induced hypertension in the rat.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

ObjectiveTo examine the role of adrenocorticotropin in the regulation of the sympathetic outflow to the muscle vascular bed in healthy female humans.DesignEight healthy, nonsmoking female subjects (aged 18–33 years) were examined before and after injection of 0.25 mg adrenocorticotropin 1–24 or placebo according to a balanced, double-blind cross-over protocol.MethodsMuscle sympathetic nerve activity, arterial pressure, and heart rate were continuously recorded both under basal conditions and during a 50 min period after injection of each substance. Furthermore, sympathoexcitatory capacities of inspiratory apneas and cold pressure tests performed before and after injection of adrenocorticotropin were determined.Results:The injection of adrenocorticotropin rapidly increased burst frequency of muscle sympathetic nerve activity (P< 0.01). The maximal effect of adrenocorticotropin, with an increase in burst frequency of 63%, occurred during the third minute after injection and waned subsequently, but muscle sympathetic nerve activity remained significantly increased during the first 10 min after injection. The stimulatory effect of adrenocorticotropin had disappeared 40 min after injection. The sympathoexcitatory capacity of a maximal inspiratory apnea and a cold pressure test, respectively, remained unchanged 10 and 45 min after the administration of adrenocorticotropin compared with control. Neither blood pressure nor heart rate was significantly affected by administration of the peptide.ConclusionsThe data establish that the stress hormone adrenocorticotropin acutely increases sympathetic outflow to the muscle vascular bed in female humans. This effect is most likely mediated via central nervous system autonomic centers. The influence of adrenocorticotropin on the sympathetic nervous system might contribute to the alteration of response to stress in the course of the development of hypertension and could also add to the hypertensiogenic effects of corticosteroids and mineralocorticoids in states with excess adrenocorticotropin.

ISSN:0263-6352    

出版商:OVID    

年代:1998

数据来源: OVID