Reactivity of the Vessels of Collapsed and Ventilated Lungs to Drugs and Hypoxia

Abstract

1. In anaesthetised cats the left lung was collapsed by obstructing a ventilating tube which had been wedged into the left bronchus. If the cat had been ventilated with oxygen beforehand, the lung became gas-free in one to five minutes. 2. Blood flow to the left lung diminished rapidly as the lung collapsed and in about ten minutes was reduced by about 65%. Pulmonary vascular resistance increased greatly and these changes persisted after denervation of the lungs. 3. Vascular resistance of collapsed lungs could be reduced substantially by several drugs (acetylcholine, small doses of histamine, theophylline ethylenediamine, isopropylnoradrenaline, adrenaline) so that it must depend to some extent on increased vascular tone. 4. Vessels of collapsed lungs constricted when the oxygen saturation of the blood reaching them was reduced. This was demonstrated in vivo both before and after denervation of the lungs and after adrenalectomy and also in isolated perfused lungs. This effect is large enough to account for the changes in the pulmonary circulation which follow collapse of a lung. The time course and magnitude of the pulmonary vasoconstriction which took place during hypoxia were similar in collapsed and ventilated lungs. 5. The effects of a number of naturally occurring vasoconstrictor substances on the pulmonary circulation were compared with the effect of hypoxia. Noradrenaline caused weak but definite vasoconstriction of the pulmonary vessels, in a majority of cats; dopamine and tyramine had a more powerful constrictor effect and 5-hydroxytryptamine a much more powerful effect. Doses of histamine also usually caused pulmonary vasoconstriction. 6. Dibenamine and phenoxybenzamine reduced greatly or abolished the pulmonary vasoconstriction which accompanies hypoxia in collapsed or ventilated lungs. Guanethidine sometimes reduced or abolished it. Dibenamine and phenoxybenzamine reduced pulmonary vascular resistance. Pulmonary vasoconstriction during hypoxia was less frequently observed in cats treated with reserpine than in normal cats. 7. Lysergic acid diethylamide did not alter the pulmonary vasoconstrictor effect of hypoxia in doses which reversed the pulmonary vasoconstrictor action of 5-hydroxytryptamine. Mepyramine did not abolish (but may have sometimes diminished) the effect of hypoxia on the pulmonary vessels, in doses which reversed or abolished the pulmonary vasoconstrictor effect of histamine.