ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo compare, using data from published studies, the efficacy of chronic inhibition of the renin–angiotensin system in inducing persistent downregulation of hemodynamic and cardiovascular structural changes in an adult rat with established genetic hypertension with the widely accepted known downregulation in young genetically hypertensive rats.Study selectionWe report on 36 studies that satisfied our inclusion criteria (angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist treatment that lowered arterial pressure levels for at least 3 weeks). Of the 24 studies concerning developing hypertensive rats, a significant number (n = 17) also examined the persistence of any hemodynamic or cardiovascular effects after withdrawal of treatment. Conversely, of 15 studies using adult rats only seven and three reported on post-treatment hemodynamic and cardiovascular structural indices respectively.ResultsDuring treatment the hemodynamic and cardiovascular structural changes produced were qualitatively and quantitatively similar in the young and adult treated rats. Critical assessment of the persistence of these effects after withdrawal of treatment again found qualitatively similar responses. However, the strength of this finding is limited by the paucity of studies concerning adult rats in which equivalent treatment durations and equipressor doses of treatments were compared between these two age groups.ConclusionsBlockade of the renin–angiotensin system appears to have an efficacy in reversing established hypertension and hypertrophy similar to that with which it prevents the development of hypertension and hypertrophy. This partial ‘cure’ of hypertension after withdrawal of treatment is clearly evident when treatment is initiated during the development of hypertension and appears to be similar even when treatment is initiated in established hypertension.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo investigate components of the haemostatic and fibrinolytic system in borderline hypertensives and hypertensives, drug-treated or not, from a defined population.Design and methodsA randomly selected sample of the population of northern Sweden, 1558 subjects aged 25–64 years, was studied. Eight per cent of them were being treated with antihypertensive drugs (trHT). Remaining subjects were classified according to their mean diastolic blood pressure (DBP). Normotension, DBP <85 mmHg, was found in 63%, borderline hypertension (bHT), DBP 85–94 mmHg, in 21% and untreated hypertension (uHT), DBP ≥ 95 mmHg, in 8% of the subjects.ResultsMean age increased from the normotensive group through the bHT and uHT groups to the trHT group, members of which were the oldest. Age-adjusted values for the body mass index, waist: hip ratio, serum triglyceride and Phadeseph plasma insulin levels increased with each level of hypertension. Plasma fibrinogen levels and plasminogen activator inhibitor type 1 activity (in men) increased stepwise from normotensives through bHT and uHT to the highest values found in the trHT group. The tissue plasminogen activator (tPA) activity in men declined strongly across the groups, trHT having the lowest fibrinolytic activity (P<0.001). tPA antigen levels increased strongly from normotensives through bHT to uHT, but then were lower in the trHT group. Even after adjustment for possible confounders, men in the uHT group had 21% higher (P= 0.027) tPA antigen levels than did the normotensives. In bHT men, the tPA antigen and plasminogen activator inhibitor type 1 activities were 14 and 24% respectively, higher (P<0.01) than those in the normotensives.ConclusionHypertension is associated with multiple metabolic and fibrinolytic disturbances that are accentuated in drug-treated hypertensives and already discernible in subjects with borderline hypertension. Decreased fibrinolysis is associated with, and possibly secondary to, metabolic disturbances linked to the insulin-resistance syndrome. The independent increase in tPA antigen in hypertensive men might indicate an endothelial dysfunction.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo compare the prediction of mortality by ambulatory blood pressure monitoring and screening blood pressure measurements in a general population.DesignA prospective cohort study.Patients and methodsWe obtained blood pressure data for 1542 subjects (565 men and 977 women) aged ≥ 40 years who were followed up for up to 8.1 years (mean 5.1 years). Subjects were subdivided into five groups according to their ambulatory and screening blood pressure levels. The prognostic significance of blood pressure for mortality was examined by the Cox proportional hazards regression model.ResultsThe association between blood pressure level and mortality was more distinctive for the ambulatory blood pressure than it was for the screening blood pressure. The risk of cardiovascular mortality increased significantly for the highest quintiles of 24 h ambulatory blood pressure, whereas there was no significant association between the screening blood pressure and the cardiovascular mortality. When both 24 h and screening blood pressure values were included in the Cox model, only the systolic ambulatory blood pressure was related significantly to the increased risk of cardiovascular mortality.ConclusionsThe ambulatory blood pressure had a stronger predictive power for mortality than did the screening blood pressure. This appears to have been the first study of the prognostic significance of ambulatory blood pressure monitoring versus screening blood pressure measurements in a general population.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo investigate phenotypic consequences of renin gene polymorphism between Lyon hypertensive (LH) and normotensive (LN) rats because previously we demonstrated cosegregation of the LH allele with increased blood pressure in a cross of LH with LN rats.DesignTwo studies were conducted. Study 1 used a cohort of male F2rats from a LH × LN cross. Eighty-two rats homozygous for the hypertensive (HH) renin gene allele were compared with 82 rats homozygous for the normotensive (NN) allele. Urinary steroid excretion was measured in 24 h urine samples collected from rats aged 6 weeks. The direct aortic blood pressure was recorded in 30-week-old rats and, after they had been killed, their kidney renin concentration (KRC) was measured. In study 2, renin, angiotensinogen and angiotensin converting enzyme plasma concentrations and renin messenger RNA (mRNA) levels were measured in renal and extra-renal tissues from 6- and 25-week-old LH and LN parental and HH and NN F2male rats.MethodsUrinary steroids and plasma components of the renin–angiotensin system (RAS) were measured using specific radioimmunoassays. mRNA levels were quantified by northern blotting.ResultsIn study 1, HH F2rats had a higher blood pressure (151.5 ± 8.2 versus 146.0 ± 7.4 mmHg,P<0.001) and a lower KRC (514 ± 203 versus 666 ± 304 μg A1/h per g cortex,P<0.01) than did NN rats aged 30 weeks. In covariate analysis the decrease in KRC in HH rats was attributable to their increased blood pressure rather than to the renin genotype. The renin genotype of rats aged 6 weeks was not associated with a change in the urinary excretion of aldosterone, desoxycorticosterone, corticosterone or 18-hydroxy desoxycorticosterone. In study 2, we found no difference either in plasma levels of RAS components or in renal or extra-renal renin mRNA levels either between parental LH and LN rats or between HH and NN F2rats apart from a higher plasma renin concentration in LH rats aged 6 weeks. Renal, but not extra-renal, renin mRNA levels declined with age.ConclusionsWe found no evidence of a renin genotypedependent phenotypic difference in the RAS that could account for the effect of the renin locus on blood pressure in Lyon rats. Our findings suggest that the effect of the locus on blood pressure might be due to an as yet unidentified gene linked to renin.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectivesOur objective was to determine the effect of nitric oxide (NO) inhibition on renal synthesis of endothelin-1 (ET-1)in vivo.Design and methodsRats were administered 500 mg/1 NG-nitro-L-arginine methyl ester (L-NAME) in their drinking water or its vehicle for 2 weeks (2W-L-NAME, n = 10; 2W-CONT, n = 10) or for 6 weeks (6W-L-NAME, n = 13; 6W-CONT, n = 11). We measured the levels of albumin, NO metabolites and ET-1 both in their blood and in 24 h urine samples, and determined the expression of preproET-1 messenger RNA in the renal cortex and the inner medulla. We also examined renal histology.ResultsL-NAME administration for 6 weeks reduced NO metabolites both in serum (21.5 versus 3.66 nmol/ml in 6W-CONT) and in urine (5.72 versus 22.53 nmol/24 h in 6W-CONT), raised the systolic blood pressure (228 versus 162 mmHg in 6W-CONT), and the increased urinary excretion of albumin (24.29 ± 11.66 versus 0.60 ± 0.08 mg/day in 6W-CONT) and of ET-1 (112.0 ± 38.3 versus 35.8 ± 4.4 pg/day in 6W-CONT). There were no significant differences between the plasma levels of ET-1 in the control and L-NAME groups. Expression of preproET-1 messenger RNA increased in the renal cortex but not in the inner medulla in the 6W-L-NAME group. Bleeding and marked arteriolar narrowing were observed in the renal cortex of the 6W-L-NAME group.ConclusionsProlonged inhibition of NO synthesis increases urinary excretion of ET-1 and albumin without having any effect on plasma ET-1 levels. These results do not support the hypothesis that NO plays an inhibitory role in the regulation of ET-1 in the systemic circulation, although it is possible that such a role could exist in renal tissue. However, in view of the albuminuria, a more likely explanation is that increased urinary ET-1 is secondary to L-NAME-induced renal hyperfiltration injury.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo determine whether cold-stress stimulation of the soles of the paws would produce a preeclampsialike syndrome in rats.MethodsPregnant or nonpregnant rats were kept in 0°C floor and 23°C room temperature cages (the cold-stressed group) or in 23°C floor and 23°C room temperature cages (the control group) for 2 weeks. Their blood pressure, proteinuria, and plasma catecholamines were measured, and histologic studies were performed on all groups.ResultsThere were no significant differences in systolic blood pressure between the two groups during the first week of the experimental period; however, during the last week of gestation the blood pressure of the cold-stressed group did not fall and was significantly higher than that of the control group. A significant increase in urinary protein excretion was observed in the cold-stimulated pregnant rats, in contrast to the control rats. The concentrations of norepinephrine and epinephrine in the cold-stressed pregnant rats were markedly higher than those in the control rats. A decrease in trophoblast invasion, congestion, and fibrinoid deposits of the labyrinth were observed in the cold-stressed rats. A marked increase in subendothelial fibrinoid deposits in the glomerular capillary was found only in the cold- stressed pregnant rats. The blood pressure, biochemical parameters, and histologic findings in the nonpregnant rats were almost the same as those in the pregnant rats.ConclusionChronic local cold stimulation of the soles of the paws induces preeclampsia-like phenomena in pregnant and nonpregnant rats, and this model suggests that the cause of preeclampsia is involved in chronic stimulation of the sympathetic nerve.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

ObjectiveTo develop and validate a technique for the continuous computerized calculation of the baroreceptor reflex sensitivity (BRS) of the heart rate in rats.DesignThe BRS was calculated from spontaneous changes in blood pressure and pulse interval using spectral analysis as well as time-series techniques. The BRS values obtained with these techniques were compared with those obtained by standard pharmacological methods.MethodsThe blood pressure and pulse interval in adult Wistar–Kyoto (WKY) rats were recorded on a beat-to-beat basis for two consecutive 30 min periods. During one of these periods the BRS was determined pharmacologically by injections of nitroprusside and phenylephrine. Measurements were performed after administration of saline as vehicle or during manipulation of the autonomic nervous system by infusion of metoprolol, methyl-atropine and hexamethonium. Sequential time-series methods for continuous BRS calculation were tested for 24 h periods in intact WKY rats as well as in WKY rats that had been subjected to sino-aortic denervation or to electrical lesioning of the nucleus tractus solitarius.ResultsThe correlation coefficient between BRS values in intact WKY rats derived from the pharmacological method and those from spectral analysis techniques was low (R2= 0.16). The correlation coefficient between BRS values from the pharmacological method and those from the developed time-series method was higher (R2= 0.64). The BRS measured using the latter method was found to vary over 24 h with the highest values during the sleeping period. After surgical elimination of the baroreflex, the algorithm returned BRS values close to zero throughout the 24 h period. The BRS estimate was found to be a measure of the parasympathetic rather than of the sympathetic component of the baroreceptor reflex.ConclusionThe developed time-series method calculates an index of the gain of the cardiac baroreflex in rats faithfully. This method can be implemented in data acquisition software, allowing continuous on-line monitoring of the cardiac baroreflex gain.

ISSN:0263-6352    

出版商:OVID    

年代:1997

数据来源: OVID