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

• Aim: Our aim was to test the hypothesis that dual endothelin receptor blockade with tezosentan attenuates hypoxia induced pulmonary vasoconstriction. Methods: 14 anaesthetised, ventilated pigs, with a mean±SEM weight of 30,5±0,6 kg, were studied, in normoxia (FiO(2) â0,21) and with tezosentan (5mg·kg(-1) ) infusion during (n=7) or before (n=7) hypoxia (FiO(2) ∼0,10). Results: Compared to normoxia, hypoxia, increased (p<0,05) pulmonary vascular resistance 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<0,02) systemic vascular resistance by 5,2±2,1 WU. Pulmonary capillary wedge pressure, mean aortic blood pressure, heart rate, cardiac output, stroke volume and blood-O(2) -consumption were unaltered (p=ns). Tezosentan infused during hypoxia, normalised pulmonary vascular resistance, decreased (p<0,05) maximally mean pulmonary artery pressure by 7,5±0,8 mmHg, systemic vascular resistance by 5,8±0,7 WU, mean aortic blood pressure by 10,8±3,0 mmHg and increased (p<0,04) stroke volume by 8,5±1,8 mL. Mean right atrial pressure, pulmonary capillary wedge pressure, heart rate, cardiac output and blood-O(2) -consumption were unaltered (p=ns). Tezosentan infused before hypoxia additionally attenuated ∼70% of the initial mean pulmonary artery pressure increase and abolished the pulmonary vascular resistance increase, without additionally affecting the other parameters. Conclusion: Dual endothelin receptor blockade during hypoxia, attenuates the "sustained" acute pulmonary vasoconstrictor response by reducing the mean pulmonary artery pressure increase by ∼62% and by normalising pulmonary vascular resistance. Pre-treatment with tezosentan before hypoxia, additionally attenuates the initial hypoxia induced mean pulmonary artery pressure rise by ∼70% and abolishes the pulmonary vascular resistance increase, during stable circulatory conditions, without affecting oxygenation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

hypoxic pulmonary vasoconstriction

pulmonary hypertension

vascular tone

pulmonary

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