Variability of Hypoxic Pulmonary Vasoconstriction in Sheep

Abstract

In a minority of conscious sheep, the hypoxic pulmonary vasoconstrictor response is blunted ("nonresponders"). The purpose of this investigation was to determine if this blunted response is related to an increased activity of H2-histamine receptors, beta-adrenergic receptors, or the generation of inhibitory prostaglandins. We measured pulmonary arterial pressure, pulmonary arterial wedge pressure, and pulmonary blood flow for the calculation of pulmonary vascular resistance (PVR) in 5 "nonresponders" and 5 sheep with a typical hypoxic pulmonary vasoconstrictor response ("responders") while breathing room air and 13% O2 (balance, N2). Arterial oxygen tension (PaO2) was also determined as a measure of the severity of hypoxia. During hypoxia, mean PVR increased by 6% (p = NS) in the "nonresponders" (PaO2, 49 +/- 4 mmHg), and by 70% (p less than 0.01) in the "responders" (mean PaO2, 46 +/- 4 mmHg). Metiamide (H2-blocker) and propranolol (beta-adrenergic blocker) pretreatments did not restore the hypoxic pulmonary vascular response in the "nonresponders," whereas pretreatment with indomethacin (prostaglandin synthetase inhibitor) caused mean PVR to increase by 48% (p less than 0.01) during hypoxia, indicating a partial restoration of hypoxic pulmonary vasoconstriction. In the "responders," the hypoxic pulmonary vascular response was not potentiated by indomethacin pretreatment (68% increase in mean PVR). We conclude that some sheep exhibit a blunted hypoxic pulmonary vasoconstrictor response caused by enhanced production of inhibitory prostaglandins.

Does Slow-reacting Substance of Anaphylaxis Mediate Hypoxic Pulmonary Vasoconstriction?1–3

“…In addition to canine and ovine models of allergic asthma (28,29), prostaglandins and other products of the cyclooxygenase pathway have been implicated in the blunting of hypoxic pulmonary vasoconstriction by endotoxin infusion in dogs (30). Similarly, the hypoxic pulmonary vasoconstrictor response is naturally blunted in a minority of sheep and can be unmasked by pretreatment with indomethacin (31). Thus, prostaglandins might play an important role in situations where the hypoxic pulmonary vascular response is blunted.…”

Pulmonary Haemodynamics during Exercise after Low and High Doses of Acetylsalicylic Acid in Sheep

“…Rubin et al [1985] reported that indomethacin, but not meclofenamate or ibuprofen caused a slight increase in rest ing PVR in intact anaesthetized dogs. Ahmed et al [1983] detected a small, but significant rise in PVR after indomethacin in sheep, but only in those not responsive to hypoxia. On the other hand, Tucker and Reeves [1975] reported that indomethacin does not affect resting PVR in anaesthe tized dogs.…”

“…This variability in response could be due to enhanced production of vasodilator prostaglandins in some sheep. This has been suggested as a mechanism to explain the blunted hypoxic vasoconstrictor re sponse in some sheep [Ahmed et al, 1983]. There are also conflicting data in the liter ature regarding the pulmonary vasocon strictor effect of different cyclo-oxygenase inhibitors.…”

Canine Nonresponders to Alveolar Hypoxic Vasoconstriction and Quantitative Restoration of the Response by Aspirin I‐3

“…Even genetic species' differences have been stressed to explain the varied responses, especially regarding the development of pulmonary hypertension due to high altitude and chronic hypoxia (Grover et a/ 1963;Ahmed et al 1983).…”