Acetylcholine's effect on vascular resistance and compliance in the pulmonary circulation

Abstract

Acetylcholine's effect on the distribution of vascular resistance and compliance in the canine pulmonary circulation was determined under control and elevated vascular tone by the arterial, venous, and double occlusion techniques in isolated blood-perfused dog lungs at both constant flow and constant pressure. Large and small blood vessel resistances and compliances were studied in lungs given concentrations of acetylcholine ranging from 2.0 ng/ml to 200 micrograms/ml. The results of this study indicate that acetylcholine dilates large arteries at low concentrations (less than or equal to 20 ng/ml) and constricts small and large veins at concentrations of at least 2 micrograms/ml. Characterization of acetylcholine's effects at constant pulmonary blood flow indicates that 1) large artery vasodilation may be endothelial-derived relaxing factor-mediated because the dilation is blocked with methylene blue; 2) a vasodilator of the arachidonic acid cascade (blocked by ibuprofen), probably prostacyclin, lessens acetylcholine's pressor effects; 3) when vascular tone was increased, acetylcholine's hemodynamic effects were attenuated; and 4) acetylcholine decreased middle compartment and large vessle compliance under control but not elevated vascular tone. Under constant pressure at control vascular tone acetylcholine increases resistance in all segments except the large artery, and at elevated vascular tone the pressor effects were enhanced, and large artery resistance was increased.

Effects of thromboxane A2 analogue on vascular resistance distribution and permeability in isolated blood-perfused dog lungs

“…Moreover, Barman and colleagues [1] have suggested recently that a ~table TxA2 analogue, U46619, constricts all pulmonary segments with greater constriction of the small vein in isolated dog lungs. Although a different TxA 2 analogue, STA2, was used in the present study [12], we confirmed the previous suggestion of U46619-induced preferential venoconstriction in dog lungs [1] and reinforced it by the reverse-perfusion procedure. However, the predominance of pulmonary venoconstriction over arterial constriction in response to TxA 2 is not consistent among animal species.…”

“…Indeed, pulmonary vasoconstriction induced by arachidonate is ascribed primarily to the cyclooxygenase products, particularly TxA2 [10, 16,18]. Moreover, Barman and colleagues [1] have suggested recently that a ~table TxA2 analogue, U46619, constricts all pulmonary segments with greater constriction of the small vein in isolated dog lungs. Although a different TxA 2 analogue, STA2, was used in the present study [12], we confirmed the previous suggestion of U46619-induced preferential venoconstriction in dog lungs [1] and reinforced it by the reverse-perfusion procedure.…”

Evidence for active control of perfusion within lung microvessels

“…Previous reports suggest that angiotensin II and U46619 cause modest venous constriction, while bradykinin causes modest relaxation (2,4). It is difficult to predict how such activity would have affected venous particle concentrations or clustering of retained particles, but it emphasizes that pulmonary microvascular perfusion may not be controlled by simple contraction and relaxation of arterioles.…”

Functions and Control of the Pulmonary Circulation

“…81 Its effects on the pulmonary circulation are likely mediated via the release of NO, and appear to depend on the concentration of acetylcholine administered. 82,83 Lower concentrations of acetylcholine cause vaso-dilation, while higher concentrations appear to cause vasoconstriction. Histamine, a major product released during mast cell degranulation, also has variable effects on pulmonary vascular tone, causing vasoconstriction in some animal models but vasodilation in others.…”