The Responses of Pulmonary and Systemic Circulation and Airway to Allergic Mediators in Anesthetized Rats

Abstract

Lung allergic diseases sometimes accompany pulmonary vaso-and broncho-constriction. Rats are currently used for the experimental study of lung allergies. However, their hemodynamic mechanisms are not fully understood. Therefore the effects of allergic mediators were determined systematically in vivo in rats in terms of pulmonary vascular resistance (PVR), airway pressure (AWP) and total peripheral resistance (TPR). We directly measured pulmonary arterial pressure, left atrial pressure, systemic arterial pressure, central venous pressure and aortic blood flow to determine PVR and TPR, as well as AWP, following injections of platelet-activating factor (PAF), histamine, serotonin, leukotriene (LT) C 4 , and prostaglandin (PG) D 2 in anesthetized open-chest artificially ventilated Sprague-Dawley (SD) rats. PVR was dose-dependently increased by consecutive administration of PAF, LTC 4 , and PGD 2 , with the maximal responsiveness being PAF>LTC 4 >PGD 2 . However, neither histamine nor serotonin changed PVR. TPR was decreased by all agents except LTC 4 which actually increased it. PAF and serotonin, but not the other agents, increased AWP. In conclusion, allergic mediators exert non-uniform actions on pulmonary and systemic circulation and airways in anesthetized SD rats: PAF, LTC 4 and PGD 2 , but not histamine or serotonin, caused substantial pulmonary vasoconstriction; LTC 4 yielded systemic vasoconstriction, while the others caused systemic vasodilatation; only two mediators, PAF and serotonin, induce airway constriction.Key words peripheral resistance; pulmonary arterial pressure; anaphylaxis; left atrial pressure; vasodilation; pulmonary vasoconstriction Rats are currently used for investigations on pulmonary allergic diseases.1-4) However, the studies on physiological characteristics of the rat pulmonary circulation were limited. The rat pulmonary vascular responses to various endogenous allergic mediators were previously examined in isolated perfused lungs [5][6][7] : platelet-activating factor (PAF) and leukotriene (LT) C 4 cause substantial vasoconstriction. In rat isolated pulmonary arteries, 8,9) serotonin showed strong constriction. However, there is no systematic study in which the effects of allergic mediators on the rat pulmonary vascular resistance (PVR) and total peripheral resistance (TPR) were determined by measuring cardiac output (CO) and the inflow and outflow pressures of the systemic and pulmonary circulations. Therefore, we measured directly and continuously CO, pulmonary arterial pressure (PAP) and left atrial pressure (LAP), along with systemic arterial pressure (SAP) and central venous pressure (CVP), in order to determine the responses of PVR and TPR to allergic mediators including PAF, histamine, serotonin, LTC 4 , and prostaglandin (PG) D 2 in anesthetized Sprague-Dawley (SD) rats. Airway pressure (AWP) was also measured to determine whether the allergic mediators cause bronchoconstriction. We hypothesized that these mediators do not exert the same directional actions on pulmonary and s...

Platelet Activating Factor (PAF): A Mediator of Inflammation

“…Hemodynamic responses following intravenous injection of PAF in anesthetized BALB/c mice showed a dose‐dependent decrease in TPR and increase in pulmonary vasoconstriction 47 . These effects much more pronounced than changes elicited by leukotriene C4, serotonin, histamine, and prostaglandin D2.…”

“…Sprague-Dawley rats injected with PAF exhibited a dose-dependent increase in PVR, which was greater than changes induced by injection of LTC4 and PGD2. 47 Airway pressures and pulmonary vascular resistance were increased by PAF.…”

“…46 Hemodynamic responses following intravenous injection of PAF in anesthetized BALB/c mice showed a dosedependent decrease in TPR and increase in pulmonary vasoconstriction. 47 These effects much more pronounced than changes elicited by leukotriene C4, serotonin, histamine, and prostaglandin D2. Infusion of PAF intravenously in conscious Swiss mice showed dose-dependent lethality (15-80 mcg/kg) which was potentiated by administration of the β-blocker, propranolol.…”