The Effect of Acetylcholine on the Human Pulmonary Circulation Under Normal and Hypoxic Conditions1

Abstract

It is generally accepted that the tone of the peripheral arterioles plays an important part in regulating the systemic blood pressure in man. Whether the small vessels of the lungs exercise similar control over the pressure in the pulmonary artery is not so certain. This uncertainty has stemmed largely from the fact that the human pulmonary vessels have exhibited an erratic response to many vasoactive drugs (1-15). As a consequence, most physiologists have concluded either that the pulmonary vessels are incapable of intrinsic changes in tone, or that the effect of such changes, if they occur, is less important in determining the pulmonary arterial pressure than is the effect of mechanical factors alone.There is, however, considerable evidence to suggest that acute hypoxia increases the pulmonary vascular tone (16)(17)(18)(19)(20). This stimulus raises the pulmonary arterial pressure by a greater amount than might be expected to result from the increase in blood flow which occurs. Moreover, the pulmonary wedge and systemic pressures are not altered (19), and there is no consistent variation in the central blood volume (19,21). From these observations it may be inferred that hypoxia constricts the vessels of the lungs.Active dilatation of these vessels has not been so adequately demonstrated. Most drugs which lower the pulmonary arterial pressure have a concomitant action on the systemic pressure, and it 1 This investigation was supported by a research grant [H-2001 (C) ] from the National Heart Institute of the is difficult to determine whether the changes in the pulmonary circulation represent a primary or a secondary effect. However, one of us (P.H.) observed that a single dose of acetylcholine can lower the pulmonary arterial pressure without affecting the pressure in the systemic vessels (22,23). The response was transient, and was found only in patients with a moderate degree of pulmonary hypertension.Since it seemed possible that this fall in pressure occurred as a result of active vasodilatation, the present project was undertaken with two objectives in view: 1) to investigate the effect of a continuous infusion of acetylcholine into the pulmonary artery of normal subjects, and 2) to inquire whether the action of the drug was enhanced when the pulmonary arterial pressure in these same subjects had been raised by making them hypoxic. METHODSEach subject was studied in the unanesthetized basal state. Respiratory studies were carried out on a previous day to acquaint the subject with the laboratory personnel and to accustom him into the effects of breathing a low oxygen mixture.Catheterization of the pulmonary artery was accomplished in the usual way (24,25). The position of the catheter was adjusted so that the tip lay just beyond the pulmonic valve. In those subjects in whom the wedged pressure was also measured, a special doublelumen catheter was used which allowed the tip to be wedged while the proximal lumen opened into the main pulmonary artery. With the catheter in place, a cannula was introduced into...

The Catecholamines in the Pulmonary Arterial Pressor Response to Acute Hypoxia*

“…However, the present study also suggests that this prospect is unlikely, since the administration of reserpine to dogs, in doses larger than those conventionally used to deplete canine tissues of norepinephrine (29), did not prevent or blunt the rise in pulmonary arterial pressure during acute hypoxia. This failure of reserpine to modify the pulmonary arterial pressor response is consistent with the persistence of this response in man in the face of surgical sympathectomy (30,31) and "chemical" denervation (32).…”

The Effect of Acetylcholine Upon Respiratory Gas Exchange in Mitral Stenosis

“…Operating to perfection, this mechanism would result in the maintenance of equal VA/QC ratios throughout the lungs even though ventilation were unevenly distributed. The infusion of acetylcholine appears to dilate preferentially pulmonary arteries which have been constricted by hypoxia (14). Thus the effect of acetylcholine would be to increase the flow of blood through the hypoxic areas of the lung and simultaneously direct the flow of blood away from the well ventilated areas.…”

Effects of Infusion of Acetylcholine on Pulmonary Vascular Resistance in Patients with Pulmonary Hypertension and Congenital Heart Disease

“…Acetylcholine, which causes local vasodilatation when injected intra-arterially into systemic vessels7 has been used recently in the study of the pulmonary circulation. [8][9][10] Rapid inactivation of this substance in the circulating blood makes possible its injection into the pulmonary artery in sufficient concentration to affect the pulmonary vessels without altering the hemodynamics of the This project was supported in part by a grant from the Minnesota Heart Association to Dr. Shepherd, and in part by grant no. H-3532, National Institutes of Health, U.S. Public Health Service.…”