Muscarinic regulation of pulmonary intravascular volume in isolated canine lungs

The influence of acetylcholine on pulmonary intravascular volume has not been clearly identified. In 14 anesthetized dogs, the pulmonary circulation was separately perfused in situ at a constant rate and drained to an extracorporeal reservoir, so that changes in total pulmonary intravascular volume could be recorded as reciprocal changes in reservoir volume. In eight animals, acetylcholine at 100 μg/min for 20 min was associated with increases in pulmonary intravascular volume (PIV) and pulmonary arterial pressure of 41 ± 5 (SE) ml (P < 0.001) and 2.0 ± 0.0 mmHg (P < 0.001; 11 infusions), respectively. These responses were abolished after atropine (6 infusions). In six animals, pulmonary venous pressure was also measured, so that total pulmonary (TPR), pulmonary arterial (PAR), and pulmonary venous (PVR) resistances could be calculated. TPR and PVR increased from 21 ± 2 to 24 ± 3 (P < 0.001) and from 7 ± 1 to 11 ± 1 mmHg · min · l^-1 (P < 0.001), respectively, while PAR did not change significantly (6 infusions). In three of the six animals, these changes were abolished by atropine (6 infusions). In the other three animals, PIV increased 56 ± 11 ml (P < 0.001) before and 47 ± 6 ml (P < 0.001) after indomethacin. The acetylcholine-associated increases in TPR and PVR were also not significantly attenuated after indomethacin. Hence, muscarinic receptor stimulation with acetylcholine is associated with an increase in pulmonary intravascular volume, which is mediated by an increase in resistance to pulmonary venous outflow. These changes are not due to release of prostanoids. In the animal with an intact circulation, it would be expected that muscarinic receptor stimulation would be associated with an increase in pulmonary intravascular volume, which would act to attenuate left ventricular end-diastolic pressure and cardiac output.