摘要:

Aim and methodsThe outcome of 1999 apparently healthy men, aged 40–59 years, initially investigated in the period 1972–1975, has previously been ascertained at 7 and 16 year follow-ups. This has now been repeated after 21 years, to determine whether seated systolic blood pressure (BP) during a bicycle ergometer exercise test adds prognostic information on cardiovascular (CV) mortality beyond that of systolic BP measured after 5 min of supine rest.ResultsAfter 21 years, 41 979 years of observation, 470 patients had died, 255 from CV causes. Supine systolic BP [2 SD increase: relative risk (RR) 1.6, 95% confidence interval (CI) 1.3–2.0,P<0.0001], 6 min exercise systolic BP (2 SD increase: RR 1.6, 95% CI 1.3–2.0,P<0.0001) on the starting workload of 600 kpm/min (≈ 100 W,5880 J/min) and maximal systolic BP (2 SD increase: RR 1.5, 95% CI 1.2–1.9,P= 0.0005) during work were all related to CV mortality when adjusting for a large number of variables measured in the present study including age, exercise capacity, heart rates, smoking habits, glucose tolerance and serum cholesterol. When including other systolic BPs in the continuous multivariate analysis, supine systolic BP (2 SD increase: RR 1.4, 95% CI 1.04–1.9,P= 0.029) and 6 min systolic BP at 600 kpm/min (2 SD increase: RR 1.4, 95% CI 1.06–1.9,P= 0.017) were independent predictors of CV death but not maximal systolic BP during exercise (2 SD increase: RR 1.0, 95% CI 0.7–1.2,P= 0.95).ConclusionThese results are different from the mortality data at 16 years, when the independent predictive effect of supine systolic BP was cancelled out by 6 min exercise systolic BP at 600 kpm/min. Twenty-one years of follow-up of 1999 apparently healthy men disclose independently predictive information on CV death, of both supine systolic BP and 6 min exercise systolic BP taken at an early moderate workload. The influence of maximal exercise systolic BP on CV death is however cancelled out by the two other systolic BPs.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundThe genes encoding angiotensin converting enzyme (ACE,I/D), α-adducin (ADD,Gly460Trp) and aldosterone synthase (AS,−344C/T) share the potential of influencing blood pressure (BP) via sodium homeostasis. However, most studies in humans focused on single-gene effects and disregarded epistasis, the suppression or potentiation of a gene by other non-allelic genes.MethodsWe studied the singular and combined effects of the aforementioned candidate genes: (1) in relation to BP, plasma renin activity (PRA) and urinary aldosterone in 1461 subjects randomly selected from a Caucasian population; and (2) in relation to the incidence of hypertension in a subgroup of 678 initially normotensive subjects followed up for 9.1 years (median).ResultsIn cross-sectional analyses, AS/CC homozygosity was associated with slightly lower systolic BP (−1.32 mmHg;P= 0.08). AS/TT homozygotes showed both lower PRA and higher urinary aldosterone excretion (P⩽0.05). In multiple-gene analyses, compared with the whole study population, ADD/Trp subjects had a higher relative risk of hypertension in the presence of the AS/T allele (1.29;P= 0.05), whereas in combination with AS/CC homozygosity ADD/Trp subjects had the smallest relative risk (0.48;P= 0.003). Hypertension developed in 229 subjects (36.6 cases per 1000 person-years). ACE/DD homozygosity, in comparison with the other ACE genotypes, was associated with increases in the incidence of hypertension, which amounted to 31% (P= 0.005) in single-gene analyses, to 59% (P= 0.004) in carriers of the ADD/Trp allele and to 122% (P= 0.0007) in AS/CC subjects. Among subjects who had both the ADD/Trp allele and the AS/CC genotype, ACE/DD homozygotes manifested a 252% (P= 0.001) higher incidence of hypertension.ConclusionsEpistatic interactions between the ACE, ADD and AS genes contribute to the prevalence and incidence of hypertension in Caucasians. The clinical relevance of the risk-conferring haplotypes identified in our prospective study was underscored by their positive predictive values, which under the assumption of a 20% life-time risk of hypertension, ranged from 29.8–40.1%.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo study candidates for liver transplant before and 6 weeks after transplant, and to elucidate the role of endothelial dysfunction and plasma endothelin concentrations in the development of hypertension.DesignProspective follow-up study.SettingInstitutional, outpatient.Patients and controlsFifteen patients (11 men, four women, mean age 46.7±13.2 years) with end-stage liver disease (ESLD) and healthy volunteers of comparable age and sex.MethodsWe performed office blood pressure readings and 24 h ambulatory blood pressure monitoring (ABPM), measurements of endothelial-dependent vasodilatation using high-resolution ultrasound in the brachial artery at rest and during reactive hyperemia, and plasma endothelin-1 assays 3 months before and 6 weeks after the transplant.ResultsOffice systolic and diastolic blood pressures increased significantly 6 weeks after liver transplantation (from 116.6±14.1 to 139.9±19.5 mmHg and from 68.6±9.5 to 84.1±9.8 mmHg, respectively; bothP<0.001). Hypertension based on office blood pressure readings increased from 6.7 to 40% (P<0.05). Mean 24 h systolic blood pressure increased from 118.7±10.3 to 140.0±19.0 mmHg (P<0.001), mean 24 h diastolic blood pressure increased from 86.0±7.7 to 104.8±13.9 mmHg (P<0.001) and heart rate increased from 74.8±10.2 to 80.2±8.2 beats/min (P<0.05). Brachial artery flow-mediated dilatation did not change throughout the study (before transplant: 4.2±4.0%; after transplant: 6.3±5.4%; NS) and did not differ from that in controls (5.2±3.8%). Plasma endothelin-1 was increased in patients with ESLD (15.3±2.6 pg/ml) compared with controls (5.6±0.4 pg/ml;P<0.001) and remained unchanged 6 weeks after liver transplantation (14.1±3.7 pg/ml).ConclusionOur results show increased blood pressure with suppressed circadian blood pressure variability in liver graft recipients 6 weeks after transplant and no change in endothelial function and plasma endothelin concentrations. Therefore, the blood pressure increase documented in our study cannot be explained by endothelial dysfunction. Twenty-four hour ABPM should be performed routinely in patients who have undergone liver transplant.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo investigate the effect of a chronic treatment with melatonin on arterial pressure and a possible improvement of the vascular muscarinic and NO synthase (NOS) pathways in spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) rats.Design and methodsMean arterial pressure (MAP), systolic (SBP), diastolic blood pressure (DBP), and heart rate (HR) were evaluated in conscious rats treated with 30 mg/kg per day of melatonin during 4 weeks. Changes in MAP were evaluated following an intravenous injection of the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME). Relaxant effects of acetylcholine (Ach), sodium nitroprusside (SNP), and the calcium ionophore A23187 were examined on mesenteric beds and aortic rings with or without treatment with melatonin.ResultsMelatonin produced a significant reduction of MAP, SBP, DBP and HR in SHR (P<0.05). l-NAME increased the MAP of melatonin-treated SHR by the same magnitude as that of WKY rats which was significantly higher than that of non-treated SHR (P<0.05). Melatonin treatment improved the maximal relaxation of mesenteric arteries to A23187 in SHR (P<0.001) to the WKY level and caused a slight increament in Ach- and A23187-induced vasodilations in aorta from SHR and WKY rats (P<0.05).ConclusionThe present study showed that melatonin exerted a bradycardic and an antihypertensive action in SHR. The enhancement by melatonin of the endothelium-dependent vasodilation (Ach and/or A23187) in mesenteric artery and aorta from SHR and WKY rats and the higher increase in MAP following l-NAME treatment in melatonin-treated SHR suggest the contribution of an improved vascular NOS pathway activity in the hypotensive effect of melatonin.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesEssential hypertension is associated with impaired endothelium-dependent vasodilation caused by oxygen free radical-induced nitric oxide (NO) breakdown. Since calcium antagonists can improve endothelial function in hypertensive patients, we tested whether this beneficial effect could be related to restoration of NO availability by antioxidant activity.MethodsIn 10 healthy subjects and 20 essential hypertensive patients, we studied forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (from 0.15–15 μg/100 ml per min), bradykinin (0.005–0.05 μg/100 ml per min), two endothelium-dependent vasodilators, and sodium nitroprusside (1–4 μg/100 ml forearm tissue per min), an endothelium independent vasodilator, in the absence and presence ofNG-monomethyl-l-arginine (l-NMMA) (100 μg/100 ml forearm tissue per min), an NO synthase inhibitor.ResultsIn controls, vasodilation to acetylcholine and bradykinin was inhibited by l-NMMA. In hypertensive patients, vasodilation to acetylcholine and bradykinin, but not to sodium nitroprusside, was blunted and resistant to l-NMMA. Hypertensive patients were randomized to a 12-week treatment with lacidipine (4–6 mg/daily) or atenolol (50–100 mg/daily) (n= 10 each group). Lacidipine but not atenolol increased the vasodilation to acetylcholine and bradykinin and restored the inhibiting effect of l-NMMA on endothelium-dependent vasodilation, without affecting the response to sodium nitroprusside. Moreover, lacidipine reduced circulating markers of oxidative stress including plasma and low-density lipoprotein (LDL) hydroperoxides, the susceptibility of LDL to Cu2+-induced oxidation and the reactive oxygen species generated from human umbilical vein endothelial cells after incubation with LDL derived from plasma of the patients.ConclusionsLacidipine increases endothelium-dependent vasodilation by restoring NO availability, and this effect possibly is related to antioxidant activity.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the post-ischemic skin blood flow response after withdrawal of antihypertensive therapy in hypertensive patients with normal blood pressure during treatment.Design and MethodsTwenty hypertensive patients (group A) with a normal clinic blood pressure (<140/90 mmHg) receiving antihypertensive treatment (any monotherapy; one pill per day for at least 6 months) had their treatment discontinued. Before medication withdrawal and 2, 4, 12 and 24 weeks thereafter, the following measurements were made: clinic blood pressure, home blood pressure (three times per week, morning and evening) and skin blood flow response to a 5 min forearm arterial occlusion (using laser Doppler flowmetry). The patients were asked to perform an ambulatory blood pressure recording at any time if home blood pressure was ⩾160/95 mmHg on two consecutive days, and treatment was initiated again, after determination of the skin hyperemic response, if daytime ambulatory blood pressure was ⩾140/90 mmHg. The same studies were performed in 20 additional hypertensive individuals in whom antihypertensive treatment was not withdrawn (group B). The allocation of patients to groups A and B was random.ResultsThe data fom 18 patients in group A who adhered strictly to the procedure were available for analysis. Seven of them had to start treatment again within the first 4 weeks of follow-up; four additional patients started treatment again during the next 8 weeks (group A1). The seven other patients remained untreated (group A2). The skin hyperemic response decreased significantly in patients in group A1 and returned to baseline values at the end of the study, when there were again receiving antihypertensive treatment. In patients in group A2 a significant attenuation of the hyperemic response was also observed. This impaired response was present even at the end of the 6 month follow-up, at which time the patients were still untreated but exhibited a significantly greater blood pressure than before drug discontinuation. The hyperemic response of patients who did not stop treatment (group B) did not change during the course of the study.ConclusionsOur findings show a decrease in the post-ischemic skin blood flow response after withdrawal of antihypertensive treatment in hypertensive patients. This impaired response may be due to the development of endothelial dysfunction, vascular remodeling, or both, and might contribute to the return of blood pressure to hypertensive values after withdrawal of antihypertensive therapy.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesIt is generally accepted that short-term (4 weeks) inhibition of the renin–angiotensin system (RAS) of young spontaneously hypertensive rats (SHR) in their pre-hypertensive phase confers long-lasting protection from fully hypertensive levels in adulthood. However, there is very little data pertaining to the effects of such treatment in adult SHR with established hypertension. Therefore, we determined the relative effects of angiotensin converting enzyme (ACE) inhibition (perindopril), AT1receptor blockade (candesartan cilexetil) and RAS-independent vasodilatation (hydralazine) and their withdrawal in adult SHR, on blood pressure measured by radiotelemetry, as well as on cardiac and vascular structure.MethodsAdult male SHR were instrumented with radiotelemetry probes to measure blood pressure and heart rate continuously. SHR were given either vehicle, perindopril (1 mg/kg per day), candesartan cilexetil (2 mg/kg per day) or hydralazine (30 mg/kg per day) at equi-effective depressor doses for 4 weeks (treatment study). Separate groups of animals were also given identical treatments but were then monitored for a further 8 weeks after drug withdrawal (withdrawal study). An indirect in-vivo assessment of whole body vascular hypertrophy (mean arterial pressure during maximum vasoconstriction) was made during and after drug withdrawal, as was the pressor activity evoked by angiotensin I and angiotensin II. The effect of antihypertensive treatment on microalbuminuria was also assessed during and after drug withdrawal. Finally, left ventricular : body weight (lv : bw) and mesenteric media : lumen ratios were determined either immediately after 4-week treatment (treatment study) or 8 weeks later (withdrawal study).ResultsPerindopril persistently lowered blood pressure in adult SHR whereas blood pressure returned to vehicle levels within approximately 4 and 15 days after withdrawal of hydralazine and candesartan cilexetil, respectively. Cardiac hypertrophy was reduced by all three treatments, but to a lesser extent by hydralazine (treatment study), and this regression of cardiac hypertrophy persisted only with both types of RAS inhibition (withdrawal study). Vascular hypertrophy, measured indirectly and directly, was also reduced by all three treatments, with perindopril and candesartan cilexetil causing hypotrophic and eutrophic remodelling, respectively (treatment study), although these changes were generally not maintained after drug withdrawal (withdrawal study). Angiotensin I-induced pressor responses were equally inhibited during treatment with either candesaran cilexetil or perindopril (and were unaffected by hydralazine) but normalized rapidly in both groups (within approximately 2–4 days) after withdrawal of RAS inhibition. In addition, there was a small age-related increase in microalbuminuria over the study period, which was not significantly affected by any treatment.ConclusionsFollowing 4-week treatment, candesartan cilexetil, perindopril and hydralazine caused similar antihypertensive effects; however, only perindopril persistently reduced blood pressure following drug withdrawal. Both types of RAS inhibition and hydralazine caused marked cardiac and vascular remodelling during treatment, whereas only the RAS inhibitors persistently regressed cardiac hypertrophy 8 weeks later. Collectively, these results indicate the importance of the RAS for the maintenance of hypertension and cardiovascular hypertrophy in adult SHR, as well as identifying differential effects of ACE inhibition and AT1receptor blockade on persistent blood pressure reduction.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo assess the effect on the cardiovascular system, of enalapril (E) or losartan (L) given since weaning during 6 or 18 months to normal rats.MethodsAnimals were divided in three groups: control (C), E-treated and L-treated; treated rats received 10 mg/kg per day of drug. Systolic blood pressure (SBP), body weight, water and food intake (WI, FI), cardiac, left ventricular and aortic weight as well as the length of the tail were recorded. NADPH-diaphorase activity was determined as a marker of nitric oxide synthase (NOS) activity in aorta, arterioles of small intestine, heart and kidney of normal rats. NOS activity was measured as optical density (OD) in the stained tissue. Nitrate + nitrite urinary excretion was measured in 24 h urine. Only significant differences (P<0.05) are reported.ResultsSBP, absolute cardiac, left ventricular and aortic weight increased with age. Both treatments delayed these increments. At 6 and 18 months, NOS activity was higher in aortic endothelium (Em) of L- and E-treated animals. Losartan treatment during 6 months also increased NOS activity in aortic smooth muscle (SM). Aortic Em NOS activity fell in the 18 months-treated and untreated animals. E increased NOS activity in the SM of intestinal arterioles at 6 months but reduced it at 18 months.ConclusionsThe fact that both E and L delayed cardiac hypertrophy/hyperplasia and aortic growth and raised aortic endothelium NOS activity indicates a protective effect on cardiovascular damage due to aging, exerted through inhibition of angiotensin II.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesSecondary hypertension is often characterized by loss of diurnal blood pressure variability. This study examined circadian (24 h) blood pressure variability in adrenocorticotrophin (ACTH)-induced hypertension in the Sprague–Dawley rat.MethodsMale Sprague–Dawley rats were randomly allocated to sham (0.9% saline, s.c.),n= (9), ACTH (0.5 μg/kg per day, s.c.,n= 8) or ACTH (100 μg/kg per day, s.c.,n= 7) in a room with a 12 h light/dark cycle (0600 h to 1800 h). A radio telemetry transducer was used to measure blood pressure in unrestrained animals over 3 control days (C1–C3) and 10 treatment days (T1–T10). Heart rate, systolic (SBP), mean arterial (MAP) and diastolic (DBP) blood pressure were continuously recorded. Body weight was measured daily and serum corticosterone concentration ([B]) prior to death.ResultsSham treatment had no effect on any parameters. ACTH 100 μg/kg per day increased SBP from 124±2 pooled control (PC) to 134±2 mmHg (T10),MAP from 105±2 to 115±2 mmHg and DBP from 87±1 to 99±2 mmHg and decreased heart rate from 305±6 to 249±5 beats/min and body weight from 299±6 (C3) to 280±8 g (T10) (allP′<0.0036). Serum [B] was higher in ACTH- (881±44 ng/ml) than sham-treated rats (384±17 ng/ml,P<0.001). There were no differences between sham treatment and ACTH 0.5 μg/kg per day. SBP, MAP, DBP and heart rate were consistently higher for ACTH 100 μg/kg per day and sham-treated animals during the dark cycle (1800 h to 0600 h) than the light cycle (0600 h to 1800 h).ConclusionsACTH 100 μg/kg per day raises blood pressure in conscious unrestrained Sprague–Dawley rats without any change in normal diurnal rhythm.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundThe objective of the present study was to characterize the spectrum of circadian blood pressure changes in type I diabetes at different stages of nephropathy by using two monitorings in each patient in order to avoid intra-individual variability.Patients and methodsA total of 80 type I diabetic subjects and the same number of age, sex and awake mean blood pressure (BP)-matched controls were included. According to urinary albumin excretion, there were 57 normoalbuminurics, 15 persistent microalbuminurics and eight proteinurics. Two 24 h ambulatory blood pressure monitorings were performed at the same urinary albumin excretion stage in absence of antihypertensive treatment for each diabetic subject and for their respective control. Blood pressure and heart rate averages during 24 h, awake, sleep, and day : night ratio were calculated.ResultsSeven of the eight proteinuric subjects were hypertensives, whereas hypertension was absent in the normoalbuminuric and microalbuminuric groups. The intra-individual reproducibility in diabetics showed repeatability coefficients for the 24 h systolic and diastolic pressure of 33 and 42%, respectively. This reproducibility for the day : night ratio was generally worse, 57% for systolic and 59% for diastolic.A progressive increment in the mean ambulatory BP was observed across the three groups of diabetics and the differences in BP observed were most evident during the night-time period. Though no differences in the 24 h circadian pattern were present between the normoalbuminurics and their controls, nocturnal differences were observed, not only in microalbuminurics for systolic BP (P<0.05), but also in proteinurics for both systolic BP (P<0.01) as well as diastolic BP (P<0.05). No differences were observed in heart rate among the diabetic groups. The non-dipping pattern in the two monitorings was observed in 80, 58, 18 and 10% of the proteinurics, microalbuminurics, normoalbuminurics and control groups,respectively.ConclusionsPersistent abnormal circadian variability seems to be an early and frequent characteristic of type I diabetics with an increased urinary albumin excretion. Although present in some normalbuminuric subjects, the frequency of this abnormality increases as the incipient nephropathy progresses. By the time proteinuria is established, nearly all subjects present the abnormal pattern.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID