摘要:

Nitric oxide and superoxide have important roles as vascular signaling molecules. Nitric oxide (NO) reacts rapidly with superoxide, producing peroxynitrite. The relative balance between these radicals has important implications for vascular pathophysiology in hypertension and other vascular disease states. However, the relationships between superoxide, NO, and peroxynitrite formation in human blood vessels remain unclear. Accordingly, we systematically measured NO, superoxide, and peroxynitrite production from human internal mammary arteries, radial arteries, and saphenous veins from 78 patients undergoing coronary bypass surgery. Basal superoxide release was detected in all vessels at similar levels. However, endothelial removal or nitric oxide synthase inhibition increased mean superoxide release, with a corresponding reduction in peroxynitrite formation. Conversely, NO donors and superoxide scavengers both reduced superoxide release, whereas only NO donors increased peroxynitrite formation. These changes were much larger in arteries that in veins, but there were striking correlations between superoxide production, NO bioavailability, and peroxynitrite formation between the vessel types. Our findings provide direct evidence for coordinated vascular signaling mediated by interactions between NO, superoxide, and peroxynitrite and have important implications for studies of the functional effects of these radicals in human blood vessels.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Vascular endothelial growth factor (VEGF) exerts vasodilation-induced hypotension as a major side effect for treatment of ischemic diseases. VEGF has 2 receptor tyrosine kinases, KDR and Flt-1. Little is known about which receptor mediates VEGF-induced hypotension. To elucidate the role of each receptor in mediating hypotension, KDR-selective and Flt-1–selective mutants were used for in vitro and in vivo studies. The KDR-selective mutant induced vascular endothelial cell proliferation comparable to VEGF, whereas the Flt-1– selective mutant had no effect on proliferation. Intravenous injection of KDR-selective mutant, Flt-selective mutant, or VEGF caused a dose-related decrease in mean arterial pressure in conscious rats. The hypotensive response to KDR-selective mutant was significantly less than that to VEGF (P<0.01) but was greater than that to Flt-selective mutant (P<0.01). Similarly, VEGF and KDR-selective mutant induced more potent vasorelaxation than Flt-selective mutant or placenta growth factor that binds Flt-1 only (P<0.01), and the vasorelaxation to KDR-selective mutant was not significantly different at low concentrations but less than that to VEGF at high concentrations. The results indicate that the vasodilation and hypotensive effect of VEGF may involve both receptors, but KDR is the predominant receptor mediating this effect. Because KDR-selective mutant induced proliferation and angiogenesis similar to VEGF but was associated with 36% attenuation in hypotension, the data suggest that the KDR-selective mutant may represent an alternative treatment for ischemic diseases.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

We have developed a new model of neurogenic hypertension in the rat, in which hypertension is caused by injecting 50 &mgr;L of 10% phenol in the lower pole of one kidney. Administration of phenol in the kidney causes an immediate and persistent rise in blood pressure (BP), norepinephrine (NE) secretion from the posterior hypothalamic nuclei (PH), and renal sympathetic nerve activity (RSNA). Because angiotensin II (Ang II) is known to stimulate central and peripheral sympathetic nervous system (SNS) activity, we have tested the hypothesis that losartan, a specific Ang II AT1receptor antagonist, may lower BP, at least in part, by SNS inhibition. To this end, we studied the effects of losartan on BP and SNS activity following intrarenal phenol injection. Central SNS activity was measured by NE secretion from the PH using a microdialysis technique, and peripheral SNS activity was measured by direct recording of renal nerve activity. At the end of the experiments, brains were isolated and interleukin (IL)-1&bgr; and nitric oxide synthase (NOS) mRNA gene expression was measured by RT-PCR in the PH, paraventricular nuclei (PVN), and locus ceruleus (LC). The intrarenal injection of phenol raised BP, as well as central and renal SNS activity, but reduced the abundance of IL-1&bgr; and neuronal NOS (nNOS) mRNA in the PH, PVN, and LC. Whether injected intravenously or in the lateral ventricle, losartan caused a significant (P<0.01) and dose-dependent inhibition of the effects of phenol on BP, NE secretion from the PH, and RSNA. Losartan also caused a significant (P<0.01) and dose-dependent rise in IL-1&bgr; and nNOS-mRNA gene expression in the PH, PVN, and LC of phenol-injected rats. In conclusion, these studies have shown that the intrarenal injection of phenol causes a rise in central and renal SNS activity and a decrease in IL-1&bgr; and nNOS-mRNA in the PH, PVN, and LC. Losartan prevented the rise in BP and SNS activity, as well as the decrease in IL-1&bgr; and nNOS mRNA abundance caused by phenol. These studies have demonstrated that the antihypertensive action of losartan in the phenol renal injury model is largely mediated by inhibition of central and peripheral SNS activity and suggest that activation of IL-1&bgr; and nNOS, 2 important modulators of central SNS activity, mediates the inhibitory action of losartan on SNS activity.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

The purpose of this study was to compare circadian blood pressure and heart rate patterns and other cardiovascular effects of nicotine delivered rapidly (via nasal spray, NNS), slowly (transdermal nicotine, TDN), by cigarette smoking (rapid delivery of nicotine plus other smoke toxins), and placebo NNS. Twelve healthy cigarette smokers were studied on a research ward when they smoked cigarettes (16 per day) or used TDN (15 mg/16 h), NNS (24 1-mg doses per day), or placebo NNS, each for 5 days. There were no significant differences in systolic blood pressure, but diastolic blood pressure was slightly increased during cigarette smoking. Plasma epinephrine, &bgr;-thromboglobulin, and fibrinogen levels were higher during cigarette smoking than with TDN. For most measurements, NNS values were intermediate between and not significantly different from those of cigarette smoking and TDN. We conclude that, at recommended doses, TDN and NNS have fewer effects on biomarkers of cardiovascular risk than does cigarette smoking.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Stress echocardiography has been shown to improve the diagnosis of coronary artery disease in the presence of hypertension, but its value in prognostic evaluation is unclear. We sought to determine whether stress echocardiography could be used to predict mortality in 2363 patients with hypertension, who were followed for up to 10 years (mean 4.0±1.8) for death and revascularization. Stress echocardiograms were normal in 1483 patients (63%), 16% had resting left ventricular (LV) dysfunction alone, and 21% had ischemia. Abnormalities were confined to one territory in 489 patients (21%) and to multiple territories in 365 patients (15%). Cardiac death was less frequent among the patients able to exercise than among those undergoing dobutamine echocardiography (4% versus 7%,P< 0.001). The risk of death in patients with a negative stress echocardiogram was <1% per year. Ischemia identified by stress echocardiography was an independent predictor of mortality in those able to exercise (hazard ratio 2.21, 95% confidence intervals 1.10 to 4.43,P=0.0001) as well as those undergoing dobutamine echo (hazard ratio 2.39, 95% confidence intervals 1.53 to 3.75,P=0.0001); other predictors were age, heart failure, resting LV dysfunction, and the Duke treadmill score. In stepwise models replicating the sequence of clinical evaluation, the results of stress echocardiography added prognostic power to models based on clinical and stress-testing variables. Thus, the results of stress echocardiography are an independent predictor of cardiac death in hypertensive patients with known or suspected coronary artery disease, incremental to clinical risks and exercise results.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

To analyze the health disparities relative to the prevalence of arterial hypertension and its therapeutic control in the active French population, in relation to occupational categories (OC), a population of 17 359 men and 12 267 women was assessed from January 1997 to April 1998. The initial phase was a cross-sectional analysis of a cohort study designed to assess the incidence of arterial hypertension in a French working population. Information was collected by the worksite physician during the annual examination. Blood pressure (BP) was measured using a validated automatic device. Among subjects with a BP ≥140/90 mm Hg, patients not treated with antihypertensive drugs were invited to have an additional BP measurement, 1 month later. Overall prevalence was 16.1% for men and 9.4% for women. Both prevalence and therapeutic control of high BP were related to OCs in this study. Prevalence of hypertension was higher and maintenance of therapeutic control lower among lower OCs. In contrast, awareness of high BP and the proportion of hypertensive subjects under current treatment were not related to OCs. Educational level and low OC were significantly related to prevalence of high BP after adjustment for obesity, excessive alcohol consumption, and sedentary lifestyle in women only. A poor BP control under treatment was related to high alcohol intake and low OC in men. In women only, however, low educational level was related to high prevalence of hypertension and poor BP control under antihypertensive treatment. Inequalities in hypertension prevalence persist, with prevalence being higher among lower OCs. Social disparities were not observed, however, in awareness of their condition among hypertensive subjects and among patients for receiving versus not receiving any treatment for hypertension. In contrast, BP control under antihypertensive treatment was lower among lower OCs.

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0194-911X    

出版商:OVID    

年代:2002

数据来源: OVID