title: Endothelin(A)-receptor antagonism attenuates pulmonary hypertension in porcine endotoxin shock.
abstract: Porcine endotoxin shock is characterized by pulmonary hypertension, decreased mean arterial pressure and deteriorated cardiac performance. These pathophysiological findings are accompanied by increased plasma endothelin-1 levels. Previous studies have shown that both the pulmonary and systemic circulation are improved by combined endothelinA- and endothelinB-receptor antagonism. This study was designed to evaluate further the specific involvement of the endothelinA-receptor in cardiopulmonary pathophysiology during endotoxin shock. In a porcine endotoxin shock model, the endothelinA-receptor antagonist PD 155080 was administered after the onset of endotoxaemia. Cardiopulmonary vascular changes, dynamic lung compliance, oxygen-related variables and plasma levels of endothelin-1-like immunoreactivity were compared with a control group receiving only endotoxin. PD 155080 counteracted the increase in pulmonary artery pressure seen in control animals. In contrast, cardiac performance was not improved. Dynamic lung compliance was not affected by PD 155080. Plasma levels of endothelin-1-like immunoreactivity increased to a similar degree in both groups. These findings indicate that the endothelin system is involved in the pathophysiology of endotoxin shock. Furthermore, the change in pulmonary circulation seen in the present shock model is to a large extent mediated by the endothelinA-receptor mechanism. In view of previous findings, the deterioration of cardiac performance may involve the endothelinB-receptor, either alone or in combination with the endothelinA-receptor.
authors.affiliation: Dept of Anaesthesiology and Intensive Care, Karolinska Hospital, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Wanecek
authors.forename: A
authors.initials: A
authors.lastname: Oldner
authors.forename: A
authors.initials: A
authors.lastname: Rudehill
authors.forename: A
authors.initials: A
authors.lastname: Sollevi
authors.forename: K
authors.initials: K
authors.lastname: Alving
authors.forename: E
authors.initials: E
authors.lastname: Weitzberg
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004149:Dioxoles / Q000627:therapeutic use*; D065128:Endothelin Receptor Antagonists; D005260:Female; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D011651:Pulmonary Artery; D044022:Receptor, Endothelin A; D012772:Shock, Septic / Q000150:complications* / Q000503:physiopathology; D013552:Swine
chemical_list: D004149:Dioxoles; D065128:Endothelin Receptor Antagonists; C093322:PD 155080; D044022:Receptor, Endothelin A