title: Effects of bradykinin, histamine and serotonin on pulmonary vascular resistance and permeability.
abstract: The effects of bradykinin, histamine and serotonin on vascular resistance and microvascular permeability were investigated in isolated cell-free perfused rabbit lungs. The capillary filtration coefficient was determined from the slope of lung weight changes over periods of venous pressure elevation before application of bradykinin (n = 6), histamine (n = 6) and serotonin (n = 6), and 5, 20 and 50 min afterwards. To prevent rapid inactivation of bradykinin by the angiotensin-converting enzyme in the pulmonary circulation, the bradykinin effects were additionally studied in the presence of the angiotensin-converting enzyme inhibitor captopril (n = 6). Bolus application of each substance resulted in a short-lasting increase in the pulmonary vascular resistance (3.7-9.1 mmHg). Which was most pronounced in the bradykinin+captopril group. The capillary filtration coefficient was significantly increased after histamine application, and to an even greater extent after serotonin application, whereas bradykinin on its own, as well as bradykinin given in the presence of captopril, had no measurable influence on capillary filtration in the lung. As a result of the bradykinin challenge, there was an immediate massive generation of prostacyclin, which could not be further augmented by a application. Histamine injection entailed a delayed onset of prostacyclin generation after the second stimulation, whereas no prostacyclin increase was measured in the serotonin-treated lungs. Thromboxane A2 generation was exclusively observed after the first serotonin application. The data exemplify different pathophysiological characteristics of bradykinin, histamine and serotonin on lung barrier function. Histamine and serotonin induce oedema formation by enhancing microvascular permeability, whereas bradykinin does not.
authors.affiliation: Institute of Anaesthesiology and Operative Instensive Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Breil
authors.forename: T
authors.initials: T
authors.lastname: Koch
authors.forename: M
authors.initials: M
authors.lastname: Belz
authors.forename: K
authors.initials: K
authors.lastname: Van Ackern
authors.forename: H
authors.initials: H
authors.lastname: Neuhof
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002196:Capillaries / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000502:physiology; D006632:Histamine / Q000494:pharmacology*; D008833:Microcirculation / Q000187:drug effects; D009924:Organ Culture Techniques; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D012701:Serotonin; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D006632:Histamine; D001920:Bradykinin