Influence of cyclo-oxygenase inhibition and of leukotriene receptor blockade on pulmonary vascular pressure/cardiac index relationships in hyperoxic and in hypoxic dogs

1. Overall mean pulmonary arterial pressure (MPAP)/cardiac index (CI) relationships were investigated in 13 pentobarbital anaesthetized dogs ventilated consecutively with a fraction of inspired O₂ (F₁o₂) of 0.4 and with a F₁o₂ of 0.1. This sequence of alternated F₁o₂ 0.4 and F₁o₂ 0.1 was repeated (1) in the dogs with a strong pulmonary pressor response to hypoxia (more than 20% increase in pulmonary vascular resistance) (n = 6) under a continuous infusion of the leukotriene receptor blocker FPL 57231 (2 mg min⁻¹ kg⁻¹), and (2) in the dogs with a weak pressor response to hypoxia (n = 7) after cyclo-oxygenase inhibition by acetylsalicylic acid (1 g intravenously). Five-point MPAP/CI plots were constructed by opening a femoral arteriovenous fistula or by stepwise inflations of an inferior vena cava balloon catheter. The MPAP/CI plots were rectilinear in all experimental conditions.

2. In responders, hypoxia was associated with an increase in MPAP over the entire range of CI studied (1–5 litres min⁻¹ m⁻²). Infusion of FLP 57231 abolished the vasoconstricting effect of hypoxia.

3. In non-responders, MPAP was not affected by hypoxia over the entire range of CI. After acetylsalicylic acid administration, hypoxia resulted in a significant rise in MPAP from 2 to 5 litres min⁻¹ m⁻².

4. Infusion of FLP 57231 decreased mean systemic arterial pressure at both F₁o₂ 0.4 and F₁o₂ 0.1, while acetylsalicylic acid had no effect on systemic haemodynamics.

5. Stability of pulmonary vascular tone at F₁o₂ 0.4 and at F₁o₂ 0.1 and reproducibility of the hypoxic pressor response was ascertained in an additional group of five dogs with CI kept constant and MPAP measurements every 6 min during four consecutive periods of 30 min (i.e. maximum time needed to generate a MPAP/CI plot) alternately at F₁o₂ 0.4 and at F₁o₂ 0.1.

6. These results suggest that pulmonary vascular reactivity to hypoxia is regulated by balanced actions of vasoconstricting leukotrienes and vasodilating prostaglandins in anaesthetized dogs. They also indicate a vasodilating effect of FPL 57231 on systemic vessels.