Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia-induced pulmonary vasoconstriction in a porcine model

作者：Hedelin P; Kylhammar D; Radegran G^*

来源：Acta Physiologica, 2012, 204(3): 419-434.

DOI：10.1111/j.1748-1716.2011.02339.x

• hypoxic pulmonary vasoconstriction
• pulmonary hypertension
• pulmonary vascular tone

Aim: Our aim was to test the hypothesis that dual endothelin receptor blockade with tezosentan attenuates hypoxia-induced pulmonary vasoconstriction. %26lt;br%26gt;Methods: Fourteen anaesthetized, ventilated pigs, with a mean +/- SEM weight of 30.5 +/- 0.6 kg, were studied, in normoxia (FiO2 0.21) and with tezosentan (5 mg kg) 1) infusion during (n = 7) or before (n = 7) hypoxia (FiO2 0.10). %26lt;br%26gt;Results: Compared to normoxia, hypoxia increased (P %26lt; 0.05) pulmonary vascular resistance (PVR) by 3.4 +/- 0.7 WU, mean pulmonary artery pressure by 13.7 +/- 1.3 mmHg, mean right atrial pressure by 1.9 +/- 0.4 mmHg and decreased (P %26lt; 0.02) systemic vascular resistance (SVR) by 5.2 +/- 2.1 WU. Pulmonary capillary wedge pressure (PCWP), mean aortic blood pressure, heart rate, cardiac output, stroke volume and blood- O2- consumption were unaltered (P = ns). Tezosentan infused during hypoxia, normalized PVR, decreased (P %26lt; 0.05) maximally mean pulmonary artery pressure by 7.5 +/- 0.8 mmHg, SVR by 5.8 +/- 0.7 WU, mean aortic blood pressure by 10.8 +/- 3.0 mmHg and increased (P %26lt; 0.04) stroke volume by 8.5 +/- 1.8 mL. Mean right atrial pressure, PCWP, heart rate, cardiac output and blood- O2consumption were unaltered (P = ns). Tezosentan infused before hypoxia additionally attenuated approx. 70% of the initial mean pulmonary artery pressure increase and abolished the PVR increase, without additionally affecting the other parameters. %26lt;br%26gt;Conclusion: Dual endothelin receptor blockade during hypoxia attenuates the ` sustained%26apos; acute pulmonary vasoconstrictor response by reducing the mean pulmonary artery pressure increase by approx. 62% and by normalizing PVR. Pre- treatment with tezosentan before hypoxia, additionally attenuates the initial hypoxia- induced mean pulmonary artery pressure rise by approx. 70% and abolishes the PVR increase, during stable circulatory conditions, without affecting oxygenation.

• 出版日期2012-3