It is unclear whether the impairment of NO-mediated dilation in hypertension is the cause or the consequence of high blood pressure. We therefore studied in isolated resistance arteries whether elevated transmural pressure affects NO-mediated dilation. Arteries (n=5-7) were perfused at hydrostatic pressures of either 45, 120 or 160 mmHg for 48 h. Subsequently, diameter and calcium responses (fura 2) were studied at a transmural pressure of 45 mmHg. Pre-exposure to 120 and 160 mmHg reduced resting diameters and minimal diameters after stimulation with noradrenaline and significantly increased corresponding intracellular free calcium levels in vascular smooth muscle. Moreover, the NO-mediated dilation in response to acetylcholine was significantly reduced although the increase in endothelial calcium was not altered. Dilations induced by the NO donor SNP were not affected. It is concluded that chronically elevated pressure per se impairs endothelial NO production by a mechanism distal to receptor-dependent calcium increases.
We created a registry to evaluate long term outcome, efficacy and adverse events for children treated wit TNF-alpha inhibitors in Switzerland. 106 patients (68 female/38 male) were included. 61 patients were treated with Etanercept (Enbrel) and 45 with Infliximab (Remicade). Concomitant treatment at baseline included corticosteroids in 26% and Methotrexate in 75% of the patients. Subjective disease activity three months after initiation of TNF-alpha was better in 81%, worse in 4% and stable in 15% of the patients. In total 24 adverse events in 21 patients were reported. Treatment with TNF-alpha inhibitors seems to be safe and effective for children and adolescents with rheumatologic diseases.
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