PURPOSE: The physiological responses of the pulmonary vasculature and airway to various vasoconstrictors were studied using isolated perfused lungs and pulmonary arteries, but these responses were not systematically studied in in vivo rats. We determined these responses and modulating effects of systemic circulation in anesthetized rats. METHODS: We measured directly pulmonary arterial pressure (PAP), left atrial pressure (LAP), aortic blood flow, and airway pressure (AWP) to determine pulmonary vascular resistance (PVR), following injections of angiotensin II (ANG II), endothelin-1 (ET-1), vasopressin, phenylephrine and thromboxane A2 mimetic U46619 in anesthetized SD rats. RESULTS: ANG II, phenylephrine and vasopressin at high doses caused strong systemic vasoconstriction and left heart overload, resulting in a transient increase in LAP and pulmonary congestion, which consequently decreased PVR. Nonetheless, prior to LAP elevation, PVR was slightly but significantly increased by ANG II and phenylephrine. In contrast, ET-1 and U46619 substantially increased PVR in the absence of LAP elevation, while vasopressin did not increase PVR. In separate experiments, PAP and AWP increased when LAP was forcedly elevated. AWP was increased by U46619 through bronchoconstriction and by the other agents through increased LAP-induced pulmonary congestion. CONCLUSION: Airway constriction is induced by U46619, and pulmonary vasoconstriction is induced strongly by U46619 and ET-1, and weakly by ANG II and phenylephrine, but not by vasopressin in anesthetized rats. ANG II, vasopressin and phenylephrine exert indirectly a transient pulmonary vasodilatory action due to pulmonary congestion evoked by strong systemic vasoconstriction, which may account for weak pulmonary pressor responses to these agents.
PURPOSE: The physiological responses of the pulmonary vasculature and airway to various vasoconstrictors were studied using isolated perfused lungs and pulmonary arteries, but these responses were not systematically studied in in vivo rats. We determined these responses and modulating effects of systemic circulation in anesthetized rats. METHODS: We measured directly pulmonary arterial pressure (PAP), left atrial pressure (LAP), aortic blood flow, and airway pressure (AWP) to determine pulmonary vascular resistance (PVR), following injections of angiotensin II (ANG II), endothelin-1 (ET-1), vasopressin, phenylephrine and thromboxane A2 mimetic U46619 in anesthetized SD rats. RESULTS:ANG II, phenylephrine and vasopressin at high doses caused strong systemic vasoconstriction and left heart overload, resulting in a transient increase in LAP and pulmonary congestion, which consequently decreased PVR. Nonetheless, prior to LAP elevation, PVR was slightly but significantly increased by ANG II and phenylephrine. In contrast, ET-1 and U46619 substantially increased PVR in the absence of LAP elevation, while vasopressin did not increase PVR. In separate experiments, PAP and AWP increased when LAP was forcedly elevated. AWP was increased by U46619 through bronchoconstriction and by the other agents through increased LAP-induced pulmonary congestion. CONCLUSION: Airway constriction is induced by U46619, and pulmonary vasoconstriction is induced strongly by U46619 and ET-1, and weakly by ANG II and phenylephrine, but not by vasopressin in anesthetized rats. ANG II, vasopressin and phenylephrine exert indirectly a transient pulmonary vasodilatory action due to pulmonary congestion evoked by strong systemic vasoconstriction, which may account for weak pulmonary pressor responses to these agents.
Authors: Jochen Steppan; Natalia Diaz-Rodriguez; Viachaslau M Barodka; Daniel Nyhan; Erica Pullins; Traci Housten; Rachel L Damico; Stephen C Mathai; Paul M Hassoun; Dan E Berkowitz; Bryan G Maxwell; Todd M Kolb Journal: Cureus Date: 2018-01-15