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Changes in nitric oxide release in vivo in response to vasoactive substances. 总被引:2,自引:0,他引:2
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1. Changes in the release of nitric oxide (NO) in vivo were studied in rats following the administration of endothelium-dependent and -independent vasodilators as well as the NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). NO production was assessed by measuring variations of nitrate in plasma by capillary ion analysis. 2. Intravenous administration of the endothelium-dependent vasodilators, bradykinin (2 and 10 micrograms kg-1 min-1) or substance P (0.3-3 micrograms kg-1 min-1) caused a transient dose-dependent hypotension followed by an increase in plasma nitrate concentration (maximal increments: 33 +/- 5% and 38 +/- 6%, for bradykinin and substance P, respectively). Prior administration of L-NAME (10 mg kg-1 min-1) inhibited the hypotension and increase in plasma nitrate caused by these substances. Intravenous administration of sodium nitrate (200 micrograms kg-1) also produced a transitory elevation in plasma nitrate which was similar in magnitude as that caused by the vasodilators. A rapid and transitory increment in plasma nitrate was observed after i.v. administration of authentic NO (400 micrograms kg-1). 3. Rats receiving the endothelium-dependent vasodilators, prostacyclin (0.6 micrograms kg-1 min-1) or adenosine (3 mg kg-1 min-1) intravenously showed a drop in blood pressure paralleled by a decrease in plasma nitrate (maximal decreases: 34 +/- 5% and 24 +/- 4%, for prostacyclin and adenosine, respectively). A similar effect on the plasmatic concentration of nitrate was observed when L-NAME (10 mg kg-1 min-1, i.v.) was administered to the animals. 4. This study demonstrates that (i) changes in plasma nitrate can be detected in vivo after stimulation or inhibition of NO synthase, (ii) an increased production of NO, measured as plasma nitrate, is related to the hypotension caused by bradykinin and substance P and (iii) a diminished concentration of plasmatic nitrate is associated to the hypotension induced by adenosine or prostacyclin (endothelium-independent vasodilators), suggesting that the L-arginine: NO pathway is capable of rapid down-regulation in response to a fall in blood pressure. 相似文献
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I. Wiklund F. Waagstein K. Swedberg Å. Hjalmarsson 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1996,10(3):361-368
Summary Quality of life in heart failure patients is receiving increased attention as a reflection of a treatment's potential secondary
benefit of general well-being and daily functioning. The Metoprolol in Dilated Cardiomyopathy (MDC) trial was conducted as
a large, multicenter trial to establish the effects of metoprolol on mortality and need for heart transplantation in patients
with symptomatic idiopathic cardiomyopathy. It was found that metoprolol was well tolerated, improved symptoms and cardiac
function, and prevented clinical deterioration in patients with symptomatic idiopathic dilated cardiomyopathy. Quality of
life was evaluated as a secondary endpoint in 345 out of 383 randomized patients using a disease-specific questionnaire, the
Quality of Life in Heart Failure Questionnaire, depicting physical activity, somatic symptoms, emotions, and life satisfaction.
In a comparison of patients treated with metoprolol or placebo, patients treated with metoprolol noted a significantly more
favorable response than those treated with placebo in terms of the overall treatment evaluation (p<0.05). Additionally, an
analysis of the changes from baseline to 18 months, using 95% confidence intervals, revealed that patients treated with metoprolol
showed a significant improvement from baseline to 18 months in life satisfaction, physical activity, and the total score,
while patients treated with placebo did not change at all. The improvement in quality of life was supported by the correlations
with improvement in traditional clinical parameters. 相似文献
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Rough estimates of the effect in 2005 of various preventive measures aimed at reducing cancer mortality in the Nordic countries were made using the American software CAN*TROL. The effect was measured as the percentage reduction in cancer mortality in 2005. The calculations were performed for changes in the smoking, dietary and sunbathing habits of the population (primary prevention), earlier diagnosis (secondary prevention) and improvements in survival resulting from better treatment (tertiary prevention). The calculations incorporate many assumptions, some of them more firmly based than others, such as uniformity of incidence trend in all the Nordic countries and also concerning the causality of various relations. For lack of evaluated Nordic data, we have used American figures concerning stage distributions and stage-specific relative survival rates. These assumptions should be borne in mind when drawing conclusions from the results obtained. The results show that there is a potential of up to several tens of percent for reducing total cancer mortality by the year 2005. 相似文献
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P. Lips MD C. Cooper D. Agnusdei F. Caulin P. Egger O. Johnell J. A. Kanis U. Liberman H. Minne J. Reeve J. Y. Reginster M. C. de Vernejoul I. Wiklund 《Osteoporosis international》1997,7(1):36-38
The morbidity of osteoporosis is caused by fractures. Vertebral fractures lead to pain and disability and a decrease in quality of life. A Working Party of the European Foundation for Osteoporosis has developed a specific questionnaire for patients with established vertebral osteoporosis. This questionnaire is intended for use in clinical trials. The questionnaire consists of questions and visual analogue scales in the following domains: pain, activities of daily living, jobs around the house, mobility, leisure and social activities, general health perception and mood. The questionnaire has been translated from English into French, German, Italian, Hebrew, Swedish and Dutch. The questionnaire is currently being validated in a multicentre study involving patients with stable osteoporosis and control subjects. Preliminary results indicate that the reproducibility is sufficient and that the questionnaire is able to discriminate between patients with vertebral osteoporosis and control subjects. 相似文献
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