摘要:

Abstract—C-reactive protein (CRP) and microalbuminuria reflect intimately related components of the atherosclerotic disease process. Epidemiological studies found only modest associations between CRP and microalbuminuria. Blood pressure, one of the components of the metabolic syndrome in the general population, is the main determinant of microalbuminuria in diabetes and hypertension. We questioned whether CRP modifies the relationship of blood pressure and other cardiovascular risk factors with microalbuminuria in a cross-sectional study in 8592 inhabitants from Groningen, The Netherlands. The crude data showed an increase in the prevalence of microalbuminuria with increasing CRP quartiles (4.8, 9.6, 14.5, and 18.6%,P<0.0001). On stratification for cardiovascular risk factors, the data revealed a significant and positive interaction between mean arterial pressure (MAP) and quartiles of CRP with respect to the risk of microalbuminuria (Wald statistic 9.2,P=0.03). In subjects with a MAP <90 mm Hg, a nonsignificant trend in the association between CRP quartiles and microalbuminuria was found (prevalence: 3.9%, 5.8%, 6.6%, 8.7%;P=0.11). This trend was much steeper and significant in subjects with an MAP >90 mm Hg (prevalence: 6.7%, 13.6%, 20.4%, 25.1%;P<0.0001). Controlling for other risk factors in multivariate analyses, the positive interaction persisted (P=0.0004). No significant interactions between other risk factors and CRP with respect to the risk of microalbuminuria were encountered. Thus, CRP modifies the relation between blood pressure and microalbuminuria.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—The Dahl rat represents a robust animal model of salt-sensitive hypertension, with Dahl S rats being salt sensitive and Dahl R rats (the Dahl S counterparts) being salt resistant for the development of hypertension. Here we evaluate the effect of reduced dietary salt intake on learning and memory in the Dahl rat model. Salt restriction produced a significant impairment in social transmission of food preference and social recognition memory in Dahl S rats without affecting spatial learning. In contrast, social transmission of food preference and social recognition memory remained unaffected in Dahl R rats, whereas navigation performance was significantly improved. This effect on learning and memory was not generalized because sodium restriction did not influence object recognition memory in either Dahl S or Dahl R rats. The significant decrement in select cognitive functions in Dahl S rats produced by salt restriction are in sharp contrast to the well known positive effect of dietary salt restriction in alleviating high blood pressure and associated target organ complications, suggesting that caution must be exercised when weighing the benefits of salt restriction in improving cardiovascular health in salt-sensitive hypertension against the potential undesirable effects of reduced cognitive function.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—The enzyme 11-&bgr; hydroxysteroid dehydrogenase type 2 plays a major role in blood pressure regulation. It metabolizes glucocorticoid hormones into derivatives with low affinity for the mineralocorticoid receptor, preventing its permanent occupancy by circulating cortisol, which is 100- to 1000-fold more abundant than aldosterone in the plasma. Inactivating mutations of the enzyme result in severe hypertension, as seen in children with apparent mineralocorticoid excess syndrome. In patients with essential hypertension, however, attempts to evidence enzyme deficiency have been inconclusive. In this pilot study, its catalytic activity was measured directly in aldosterone-sensitive sweat gland ducts collected from skin biopsy samples of 10 male normotensive subjects and 10 subjects with essential hypertension (more than 140 to 90 mm Hg) with no sign of hypermineralocorticism. Isolated ducts were assayed for nicotinamide-dinucleotide-dependent dehydrogenase activity (transformation of tritiated corticosterone into tritiated-11 dehydrocorticosterone, as measured by high-pressure liquid chromatography). Hypertensive patients exhibited significantly lower 11-&bgr; hydroxysteroid dehydrogenase type 2 activity (9.7±4.7 femtomoles per 3 mm length of duct and per 10 minutes incubation, median±SD) than did normotensive subjects (15.9±2.6). Such defect was undetectable using the classical urinary corticosteroid metabolism indexes, probably because of compensatory mechanisms. Relations between these findings and blood pressure levels should benefit from direct enzyme measurements in the vasculature. In conclusion, this cross-sectional study points to partial 11-&bgr; hydroxysteroid dehydrogenase type 2 deficiency as a novel feature of essential hypertension, which should stimulate search for new signaling pathways and therapeutical targets.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Salt supplementation improves orthostatic tolerance in many patients with posturally related syncope (PRS). This study aimed to examine whether in those patients who responded to salt loading there was also evidence of improved cerebral autoregulation and more powerful peripheral vasoconstriction during orthostasis. Eleven PRS patients were studied before and after ingestion of 100 mmol/d slow sodium for 2 months. Subjects underwent an orthostatic stress test of combined head-up tilting and lower body suction. We continuously monitored heart rate (ECG), blood pressure (Finapres), forearm and cerebral blood flow velocities (Doppler ultrasound), and end-tidal carbon dioxide (CO2). Forearm vascular resistance was calculated from pressure divided by velocity. Cerebral autoregulation was assessed from the correlation coefficient of the relationship between cerebral blood pressure and velocity. Salt loading had no effect on resting heart rate or blood pressure. Symptoms and orthostatic tolerance significantly improved in 10 of the patients. This was associated with a significant increase in the maximal forearm vasoconstriction from 64.4%±13.7% (SEM) to 135.2%±23.9% (P<0.005). The relationship between cerebral velocity and pressure was less strong (before salt:r=0.74±0.8; after salt:r=0.41±0.1;P<0.02), indicating improved autoregulation. End-tidal CO2levels were not different between the 2 tests. Salt loading in PRS patients increases orthostatic tolerance and improves cerebrovascular and peripheral vascular control without affecting blood pressures. These changes are likely to contribute to the beneficial effects of salt loading in these patients.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—We examined the effects of sleep microstructure, ie, the cyclic alternating pattern (CAP), on heart rate (HR)- and blood pressure (BP)-regulating mechanisms and on baroreflex control of HR in healthy humans and tested the hypothesis that sympathetic activation occurring in CAP epochs during non-rapid eye movement (non-REM) sleep periods is buffered by the arterial baroreflex. Ten healthy males underwent polysomnography and simultaneous recording of BP, ECG, and respiration. Baroreflex sensitivity (BRS) was calculated by the sequences method. Autoregressive power spectral analysis was used to investigate R-R interval (RRI) and BP variabilities. During overall non-REM sleep, BP decreased and RRI increased in comparison to wakefulness, with concomitant decreases in low-frequency RRI and BP oscillations and increases in high-frequency RRI oscillations. These changes were reversed during REM to wakefulness levels, with the exception of RRI. During CAP, BP increased significantly in comparison to non-CAP and did not differ from REM and wakefulness. The low-frequency component of BP variability was significantly higher during CAP than non-CAP. RRI and its low-frequency spectral component did not differ between CAP and non-CAP. BRS significantly increased during CAP in comparison to non-CAP. BRS was not different during CAP and REM and was greater during both in comparison with the awake state. Even during sleep stages, like non-REM sleep, characterized by an overall vagal predominance, phases of sustained sympathetic activation do occur that resemble that occurring during REM. Throughout the overnight sleep period, the arterial baroreflex acts to buffer surges of sympathetic activation by means of rapid changes in cardiac vagal circuits.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Because inhibition of neuronal nitric oxide synthase in the nucleus tractus solitarii blocks cardiovascular responses to activation of local glutamate receptors, and because glutamate is a neurotransmitter of baroreceptor afferent nerves, we sought to test the hypothesis that neuronal nitric oxide synthase inhibition would block baroreflex transmission and cause hypertension. We determined reflex heart rate responses to intravenous phenylephrine and sodium nitroprusside in 5 anesthetized rats before and after bilateral microinjection (100 nL) of the neuronal nitric oxide synthase inhibitor AR-R 17477 (7.5 nmol) into the nucleus tractus solitarii. The inhibitor significantly increased mean arterial pressure without affecting heart rate, and it significantly reduced the gain of the baroreflex. After administration of the inhibitor, reflex responses of heart rate to changes in mean arterial pressure were always less than those responses to the same, or less, change in mean arterial pressure in the same animal without administration of the inhibitor. Microinjection of saline (100 nL) bilaterally into the nucleus tractus solitarii did not lead to hypertension or change baroreflex responses. These data support the hypothesis and suggest that neuronal nitric oxide synthase is critical to transmission of baroreflex signals through the nucleus tractus solitarii.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Small follow-up studies of hospital-based series indicate women with preeclampsia have an increased risk of insulin resistance postpartum. However, long-term data are lacking among women with gestational hypertension without proteinuria. Using a general population-based sample of 5889 women from Northern Finland followed longitudinally since birth in 1966, we examined these associations and the influence of the subject’s own birth weight and gestational age on this relationship. At age 31, blood pressure was measured and blood samples collected from 2678 women, of which 1463 women had had at least 1 singleton pregnancy. Of these, 45 had been hospitalized because of gestational hypertension and 49 because of preeclampsia. Women who had had either gestational hypertension or preeclampsia during their first pregnancy (average age 25 years) had increased blood pressure at 31 years compared with women with previous normotensive pregnancy, even after adjustment for body mass index (P<0.001 in gestational hypertension,P=0.023 in preeclampsia group). When compared with the whole female population, women with previous gestational hypertension at same age still had higher blood pressure, while this difference was weaker for women with previous preeclampsia. Women with gestational hypertension and preeclampsia also had higher waist circumference, waist/hip ratio, and body mass index, as well as increased serum insulin levels and lower glucose/insulin ratio than women with previous normotensive pregnancy. The associations remained after adjustment for participant’s own birth weight or gestational age. Women born before gestational week 37 had a 2-fold risk for gestational hypertension in their first pregnancy (RR: 2.53; 95% CI: 1.0, 6.2).

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—A chronic reduction in uterine perfusion pressure in the pregnant rat is associated with significant elevations in mean arterial pressure, proteinuria, and reductions in kidney function as is chronic nitric oxide blockade, suggesting that nitric oxide deficiency may contribute to the clinical manifestations of preeclampsia. The purpose of this study was to determine whether supplementation with l-arginine, the precursor for nitric oxide, attenuates the hypertension produced in response to a chronic reduction in uterine perfusion pressure in the pregnant rat. Reduced uterine perfusion was initiated at day 14 of gestation with arterial pressure determined at day 19 of gestation in conscious, chronically instrumented rats. Arterial pressure was significantly elevated in pregnant rats with chronic reductions in uterine perfusion as compared with pregnant control rats (132±2 versus 109±2 mm Hg,P<0.01, respectively). Treatment with l-arginine (2%) in the drinking water was initiated at day 10 of gestation. l-arginine supplementation resulted in a significant decrease in arterial pressure in both pregnant rats with reduced uterine perfusion pressure (113±2 mm Hg treated,P<0.01 versus untreated pregnant with reduced uterine perfusion pressure) and pregnant control (97±3 mm Hg treated,P<0.01 versus untreated pregnant) rats. However, supplementation with l-arginine decreased blood pressure by 19 mm Hg in pregnant with reduced uterine perfusion pressure (untreated versus treated) as compared with 12 mm Hg in pregnant (untreated versus treated) rats. Thus, these results suggest that l-arginine supplementation may be beneficial in attenuating the hypertension in preeclampsia.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—A simple and economical technique was developed to isolate and culture human arterial smooth muscle cells from chorionic plate vessels. Placentas from healthy women were collected at the time of term delivery. Chorionic plate arteries were identified, excised, and cut into small pieces. An explant technique was used to grow cultures of placental arterial smooth muscle (PASM) cells. Small pieces of vessel with lumens down were placed in 100-mm culture plates and grown in Dulbecco modified eagle medium and 10% fetal bovine serum. Cells appeared from explants within 1 week and grew to confluence in approximately 4 weeks. At confluence, PASM cell cultures had a uniform cell morphology that was characterized by elongated cells in parallel rows, typical of smooth muscle cells. Smooth muscle cell phenotype was evaluated by morphology and by immunoblotting and immunofluorescence of smooth muscle myofilament proteins. All PASM cell cultures expressed &agr;-smooth muscle actin, &bgr;-tropomyosin, and h-caldesmon. Expression was similar to that of human aortic smooth muscle cells, but not to endothelial cells or fibroblasts. PASM cells stained uniformly for &agr;-smooth muscle actin and lacked staining for a fibroblast-specific antigen. PASM cells were evaluated for their response to inflammatory mediators, tumor necrosis factor-&agr;, and interleukin-1&bgr; by measurement of interleukin-8 production. Cells cultured for 18 hours showed a progressive increase in interleukin-8 production with time. Treatment with inflammatory mediators increased interleukin-8 production by 3-fold as compared with media control. This technique provides a simple method to obtain normal human arterial smooth muscle cells for in vitro studies of physiology and pathophysiology.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID

摘要:

Abstract—Studies were performed to test the hypothesis that reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) contribute to the pathogenesis of aldosterone/salt-induced renal injury. Rats were given 1% NaCl to drink and were treated with one of the following combinations for 6 weeks: vehicle (0.5% ethanol, SC, n=6); aldosterone (0.75 &mgr;g/H, SC, n=8); aldosterone plus a selective mineralocorticoid receptor antagonist; eplerenone (0.125% in chow, n=8); aldosterone plus an antioxidant; and tempol (3 mmol/L in drinking solution, n=8). The activities of MAPKs, including extracellular signal-regulated kinases (ERK)1/2, c-Jun-NH2-terminal kinases (JNK), p38MAPK, and big-MAPK-1 (BMK1) in renal cortical tissues were measured by Western blot analysis. Aldosterone-infused rats showed higher systolic blood pressure (165±5 mm Hg) and urinary excretion of protein (106±24 mg/d) than vehicle-infused rats (118±3 mm Hg and 10±3 mg/d). Renal cortical mRNA expression of p22phox, Nox-4, and gp91phox, measured by real-time polymerase chain reaction, was increased in aldosterone-infused rats by 2.3, 4.3, and 3.0-fold, respectively. Thiobarbituric acid-reactive substances (TBARS) content in renal cortex was also higher in aldosterone (0.23±0.02) than vehicle-infused rats (0.09±0.01 nmol/mg protein). ERK1/2, JNK, and BMK1 activities were significantly elevated in aldosterone-infused rats by 3.3, 2.3, and 3.0-fold, respectively, whereas p38MAPK activity was not changed. Concurrent administration of eplerenone or tempol to aldosterone-infused rats prevented the development of hypertension (127±2 and 125±5 mm Hg), and the elevations of urinary excretion of protein (10±2 and 9±2 mg/day) or TBARS contents (0.08±0.01 and 0.11±0.01 nmol/mg protein). Furthermore, eplerenone and tempol treatments normalized the activities of ERK1/2, JNK, and BMK1. These data suggest that ROS and MAPK play a role in the progression of renal injury induced by chronic elevations in aldosterone.

ISSN:0194-911X    

出版商:OVID    

年代:2004

数据来源: OVID