Haemodynamic and neuroendocrine effects of tezosentan in chronic experimental pulmonary hypertension.

Intensive Care Medicine
André P LourençoAdelino F Leite-Moreira

Abstract

Chronic pulmonary hypertension (PH) therapy is poorly investigated in intensive care. Our aim was to evaluate haemodynamic and neuroendocrine effects of the dual endothelin-1 (ET-1) blocker tezosentan in monocrotaline (MCT)-induced PH. Male Wistar rats (180-200 g, n = 194) randomly received 60 mg kg(-1) MCT or vehicle, subcutaneously, and 2 days later, a subgroup of MCT-injected rats was gavaged with 300 mg kg(-1) day(-1) bosentan (MCT BOS, n = 46), while another (MCT, n = 125) and control rats (Ctrl, n = 23) received vehicle. At 25-30 days, 48 h after interrupting bosentan, rats randomly underwent either a dose-response evaluation (0.5-20 mg kg(-1), n = 7 each group) or a 4 h perfusion of tezosentan (20 mg kg(-1) in 10 min + 10 mg g(-1) h(-1)) or vehicle (n = 8 per group, each). Haemodynamics, including blood gas analysis, were evaluated after thoracotomy under anaesthesia. After plasma, right ventricle (RV) and lung collection, plasma ET-1, cytokines, nitrate and 6-keto-PGF1α, and lung and right ventricular gene expression and cyclooxygenase (COX) and nitric oxide synthase (NOS) activities were quantified. Monocrotaline resulted in PH, RV dilation and decreased cardiac output (CO) that were attenuated in MCT BOS. Pulmonary hy...Continue Reading

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Citations

Feb 28, 2014·European Journal of Heart Failure·Adelino F Leite-MoreiraCarlo G Tocchetti
Jul 31, 2016·American Journal of Physiology. Heart and Circulatory Physiology·Mohamed AlaaAndré P Lourenço
Aug 11, 2017·Journal of Cardiovascular Pharmacology and Therapeutics·Marta Tavares-SilvaAndré P Lourenço

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