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期刊名称: British Journal of Pharmacology
Volume:135(4)     2002
ISSN:0007-1188;

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作者 : Graeme A Deuchar ;   Andrew Docherty ;   Margaret R MacLean ;   Martin N Hicks ;  
发表期刊 : British Journal of Pharmacology
ISSN : 0007-1188;
出版时间 : 2002
卷期 : 135(4)
起始页码 : 1060
终止页码 : 1068
摘要 : Using anin vivomodel of pulmonary hypertension (PHT) secondary to left ventricular dysfunction (LVD), the pulmonary arterial response to the nitric oxide synthase (NOS) blockerL-NAME (30?μmol.min?1i.v.) and the subsequent responses to cumulatively administered endothelin-1 (ET-1) (0.001?–?4?nmol.kg?1i.v.) or big ET-1 (0.1?–?2.0?nmol.kg?1i.v.) were studied. Additionally, the effect of the non-selective ET-1 receptor antagonist, SB209670, was investigated.Eight weeks after coronary artery ligation or sham operation, rabbits demonstrated increased mean pulmonary arterial pressure (PAP) accompanied by right ventricular hypertrophy.Blockade of NOS caused a greater increase in basal PAP (increased by 7.7±1.1?mmHgc.f. 3.8±1.0?mmHg in controls,P<0.05) and uncovered a greater pulmonary pressor response to exogenous ET-1 in rabbits with PHT (increased by 10.2±2.3?mmHgc.f. 4.9±1.0?mmHg in controls,P<0.05).Big ET-1 evoked a pulmonary pressor effect, in both groups of rabbits, that was increased following blockade of NOS and was more potent in rabbits with PHT.The non-selective ET-1 receptor antagonist, SB209670, reduced basal PAP (from 16.9?mmHg to 15.9?mmHg,P<0.05) in rabbits with PHT and blocked the response to ET-1 in the presence ofL-NAME.In conclusion, the results demonstrate that basal NO activity masks a pulmonary pressor response to exogenously administered ET-1. An increased responsiveness to ET-1 was shown in the pulmonary arterial bed of rabbits with PHT secondary to LVD, implicating a pathophysiological role for ET-1 in this model.

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