OBJECTIVE -One of the earliest signs of vascular change is endothelial dysfunction, which is also known to provoke albuminuria and to predict cardiovascular prognosis. The aim of this study was to analyze the effects of renin-angiotensin system (RAS) blockade on renal endothelial function.RESEARCH DESIGN AND METHODS -In a multicenter, prospective, double-blind, forced-titration, randomized study, 96 patients with type 2 diabetes, hypertension, glomerular filtration rate Ͼ80 ml/min, and normo-or microalbuminuria were treated once daily with 40/80 mg telmisartan or 5/10 mg ramipril for 9 weeks. RESULTS -The mean, reflecting the magnitude of nitric oxide (NO) activity, increased with telmisartan from 71.9 Ϯ 9.0 ml/min before therapy to 105.2 Ϯ 9.7 ml/min at the end of treatment (P Ͻ 0.001). With ramipril, RPF response to L-NMMA increased from 60.1 Ϯ 12.2 to 87.8 Ϯ 9.2 ml/min (P ϭ 0.018). The adjusted difference between treatments was Ϫ17.1 Ϯ 13.7 ml/min (P ϭ 0.214). In accordance, telmisartan increased RPF at rest (i.e., without L-NMMA) from 652.0 Ϯ 27.0 to 696.1 Ϯ 31.0 ml/min (P ϭ 0.047), whereas ramipril produced no significant changes in RPF. The more the basal NO activity improved, the greater was the vasodilatory effect on renal vasculature (r ϭ 0.47, P Ͻ 0.001).CONCLUSIONS -In patients with type 2 diabetes, telmisartan and ramipril both increased NO activity of the renal endothelium significantly, which in turn may support the preservation of cardiovascular and renal function. Diabetes Care 30:1351-1356, 2007T he close link between cardiovascular and renal changes due to cardiovascular risk factors, such as arterial hypertension and diabetes, has stimulated increasing interest (1-3). Albuminuria and decreased renal function, which are both primarily known to predict renal outcome, have now been identified as excellent predictors of cardiovascular morbidity and mortality (2-4). Most surprisingly, their predictive power surpasses that of classic risk markers of cardiovascular and atherosclerotic disease (5). Albuminuria is related to intrarenal hydraulic pressure, podocyte function, electric charge, and increased permeability, provoked by endothelial dysfunction (6). Prospective studies have demonstrated the predictive value of endothelial dysfunction for future cardiovascular morbid events when assessed in the peripheral and coronary circulation (7-9) and most likely, although not yet proven, in the renal circulation.The endothelium is a major regulator of vascular homeostasis, with functional integrity being essential for the maintenance of blood flow and antithrombotic activity (10). Nitric oxide (NO), formed from L-arginine in the presence of NO synthase, is released by the vascular endothelial cells and brings about relaxation of vascular tissue and inhibition of platelet aggregation and adhesion (11). Endothelial dysfunction occurs as a result of impairment of NO synthesis or increased NO degradation and has been detected in patients with hypertension, peripheral arterial occlusive disease, and chronic re...

Abstract-We have reported that high job strain was associated with a significantly higher diastolic blood pressure (DBP) of 4.5 mm Hg during the working hours, irrespective of BP reactivity to a stress test. We report the final results of the first 5-year follow-up study, which aimed to assess the respective influences of perception of professional strain and cardiovascular reactivity to a mental stress test on BP. A cohort of 292 healthy subjects (meanϮSEM age, 38Ϯ1 years) was followed up for progression to hypertension outcome, which was defined as an increase in systolic blood pressure (SBP) or DBP Ͼ7 mm Hg or a DBP Ͼ95 mm Hg during follow-up. None of the subjects was lost to follow-up, and 209 subjects completed the study. The high-strain (HS) group, representing 20.9% of the subjects, was compared with the remaining subjects (non-high-strain [NHS]). Similarly, the subjects with the highest BP stress reactivity (HR; 20.9% of subjects) were compared with the remaining subjects (NHR). Progression to hypertension was reached by 93 subjects (31.8%). Kaplan-Meier survival estimates revealed that neither HS nor HR increased the incidence of progression to hypertension. End-of-follow-up 24-hour ambulatory BPs that were similar in HS and NHS (120Ϯ2 vs 120Ϯ1 mm Hg, respectively) and in HR and NHR (122Ϯ2 vs 120Ϯ1 mm Hg, respectively) confirmed our findings. Age, alcohol, salt diet, body mass index, and occupation did not interfere with our results. In conclusion, cardiovascular HR and HS do not appear to be major risk markers for future high BP in healthy, young adults. Key Words: epidemiology Ⅲ stress Ⅲ clinical trials Ⅲ hypertension, essential Ⅲ blood pressure monitoring, ambulatory P sychological stress is hypothesized as 1 of the major environmental factors implicated in the genesis of hypertension. Among various psychological stresses, the most investigated has been job-related stress. It was defined by Karasek et al 1 as the combination of high psychological demand and low latitude on the job. To date, only 3 studies designed to assess the long-term effect of job strain on blood pressure (BP) have produced controversial results. 2-4 The most convincing 1 was a case-control study, which found that high job strain was associated with a 3-year increase in systolic BP (SBP)/diastolic BP (DBP) of 5/3 mm Hg, supporting the hypothesis that job strain might be an etiologic factor in the genesis of essential hypertension. 4 The effects of stressors on cardiovascular regulation involve 2 components that have never been studied concomitantly. The first component is individual stress perception, quantified by questionnaires, and the second is individual cardiovascular reactivity to stress, assessed by a BP surge in response to stress tests. We recently reported the results of a cross-sectional analysis 5 of a prospective study in which subjective perception of job strain was evaluated by the questionnaire developed by Karasek et al, 1 and stress cardiovascular reactivity was measured by the Stroop stress test. The main re...

Abstract-The baroreflex that acts to blunt blood pressure (BP) variations through opposite variations in heart rate should limit the BP increase produced by an emotional challenge. However, relations between baroreflex sensitivity and BP reactivity induced by a psychological stress in a large group of adults have never been firmly established. In 280 healthy men, rest (10 minutes) and stress (5 minutes) BP and heart rate were recorded beat to beat by a blood pressure monitor. The mental stress was elicited by a well-standardized computerized version of a word color conflict stress test (Stroop Color Test). Rest and stress baroreflex sensitivity was assessed by the cross-spectral analysis of BP and heart rate and by the sequence method. The stress-induced increase in systolic BP (22.4Ϯ0.1 mm Hg) was not correlated with resting baroreflex sensitivity but was slightly correlated (rϭ0.2, PϽ0.001) with BP variability assessed either by standard deviation or by mid-frequency band spectral power. Our results suggested that a centrally mediated sympathetic stimulation overcame cardiac autonomic regulation and emphasized the role of the sympathetic vasoconstriction in the pressure response at the onset of the stressing stimulation. During the sustained sympathoexcitatory phase, the cardiac baroreflex blunts BP variations but at a lower sensitivity. Key Words: baroreflex Ⅲ blood pressure Ⅲ men Ⅲ spectral analysis Ⅲ stress, mental B lood pressure (BP) reactivity to stress was reported to be associated with an unfavorable cardiovascular risk profile in men 1 and to be predictive of future hypertension 2 and carotid atherosclerosis in women. 3 Furthermore, a depressed baroreflex sensitivity (BRS) was significantly associated with bad cardiovascular prognosis. 4 The baroreflex, which acts to blunt BP variations through opposite variations in heart rate (HR), should limit BP increase to an emotional challenge. Parati et al 5 reported that BP variability in humans after atropine administration was decreased at rest but was increased during a physical challenge. Thus, BP reactivity to challenge may not be related to BP regulation in resting conditions. However, to our knowledge, no study has investigated relations between resting cardiac BRS and BP response during a sympathetic stimulation induced by a psychological stress in a large group of adults. Therefore, the present study aimed to clarify relations that could exist between sympathetically induced increases in BP and HR and indices of cardiac autonomic control, including BRS, in a large sample of normotensive men. Furthermore, because BRS variation during stress is controversial, 6 -8 the second purpose of the present study was to investigate BRS variations during a well-standardized mental stress. This study was carried out by using techniques developed in our laboratory. The sympathetic stimulation was elicited by use of a computerized version of the Stroop word color conflict stress test (CWT), which has been reported to provoke a steady and reproducible increase in HR ...

Abstract-Psychological stress has been reported to be related to higher blood pressure (BP) and unfavorable cardiovascular profile. However, because of the complexity of personal stress management, a multilevel stress measurement strategy is needed. The aim of this cross-sectional study was to analyze the respective influences of the subjective perception of professional strain (high demand and low latitude) and cardiovascular reactivity to a stress test (Stroop stress test) on BP. Worksite BP was measured in 303 healthy normotensive subjects, 18 to 55 years of age, who worked in the same chemical company. In a subset of 70 randomly selected subjects, 24-hour ambulatory BP was performed to assess BP during working hours. The 20% of subjects who reported the highest job strain (high-strain group) or the highest BP stress reactivity (high-responder group) were compared with the remaining subjects (80%) (non-high-strain or low-responder groups). Subjects who submitted to the highest job strain had significantly higher ambulatory diastolic BP (4.5 mm Hg, Pϭ0.015) during only working hours, whereas BP was similar during the remaining hours. Worksite BP and stress cardiovascular reactivity were similar between job strain groups. BP stress reactivity did not influence worksite and ambulatory BP. Spontaneous BP variability assessed by standard deviation and spectral analysis was equivalent between complementary groups. Prevalence of microalbuminuria was significantly higher in the high-responder group (8.2% versus 2.5% in low responders) and only slightly higher in the high-strain group (6.2% versus 3.2% in non-high strain). Potential confounding factors, such as age, gender, alcohol consumption, salt intake, body mass index, and occupation, which were equivalent between groups, did not interfere with our results. Our study quantifies high-professional strain effects on BP levels that appear to be higher only during the working period and to be independent from spontaneous BP variability and stress BP reactivity. Key Words: stress Ⅲ blood pressure, ambulatory Ⅲ job strain Ⅲ microalbuminuria T he term "stress" is widely used by behavioral and biomedical scientists, but there is no consensus as to the scientifically precise definition of the concept. Selye's 1 basic concept of an organism's response to stress, the "general adaptation syndrome," infers that any kind of environmental strain results in a common defensive reaction that is the result of sympathetic activation leading to catecholamine release. However, physiological studies proved that the hormone response (epinephrine, norepinephrine, and steroids) may vary among the nature of stimulus. More recently, the psychological perception of stress has been emphasized because stress perception may differ among individuals. Psychological stressors are filtered by cognitive appraisal mechanisms before causing a biological response; thus, for the same strain, individual effects may differ. Because a multilevel measurement strategy is needed to quantify stress, 2 in this s...

1. A new method was developed to evaluate cardiac baroreflex sensitivity. The association of a high systolic blood pressure with a low heart rate or the converse is considered to be under the influence of cardiac baroreflex activity. This method is based on the determination of the statistical dependence between systolic blood pressure and heart rate values obtained non-invasively by a Finapres device. Our computerized analysis selects the associations with the highest statistical dependence. A 'Z-coefficient' quantifies the strength of the statistical dependence. The slope of the linear regression, computed on these selected associations, is used to estimate baroreflex sensitivity. 2. The present study was carried out in 11 healthy resting male subjects. The results obtained by the 'Z-coefficient' method were compared with those obtained by cross-spectrum analysis, which has already been validated in humans. Furthermore, the reproducibility of both methods was checked after 1 week. 3. The results obtained by the two methods were significantly correlated (r = 0.78 for the first and r = 0.76 for the second experiment, P < 0.01). When repeated after 1 week, the average results were not significantly different. Considering individual results, test-retest correlation coefficients were higher with the Z-analysis (r = 0.79, P < 0.01) than with the cross-spectrum analysis (r = 0.61, P < 0.05). 4. In conclusion, as the Z-method gives results similar to but more reproducible than the cross-spectrum method, it might be a powerful and reliable tool to assess baroreflex sensitivity in humans.