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Endotoxemic pulmonary hypertension is largely mediated by endothelin-induced venous constriction.

Abstract：

OBJECTIVE:To analyze the effect of endothelin-1 on pulmonary arterial and venous contractile force in vitro and on up- and downstream pulmonary vascular resistance in vivo under sham and endotoxemic conditions in pigs. MATERIALS AND METHODS:In vitro: paired preparations of pulmonary arteries and veins were mounted in a myograph (n=13) for measurements of contractile responses to increasing concentrations of phenylephrine, endothelin-1, and sarafotoxin (endothelin receptor type B agonist). In vivo: 20 pigs were anesthetized, mechanically ventilated, and subjected to phenylephrine (reference substance), endothelin-1, sarafotoxin, endotoxin, and tezosentan (dual endothelin receptor antagonist). Hemodynamic and gas-exchange variables were monitored. Pulmonary capillary pressure, used for calculation of upstream and downstream vascular resistance, was assessed by the pulmonary vascular occlusion technique. MEASUREMENTS AND RESULTS:Pulmonary veins were more sensitive than arteries to endothelin-1 both in vitro and in vivo. This difference was more pronounced with sarafotoxin, where almost no arterial effects were noted. In vivo and in vitro exposure to phenylephrine resulted in selective arterial constriction. Endotoxin infusion resulted in pulmonary hypertension with a clear downstream dominance. The latter changes including the increase in capillary pressure were totally abolished by intervention with the dual endothelin receptor antagonist tezosentan. CONCLUSIONS:The endothelin system is extensively involved in endotoxemic pulmonary venous hypertension, an effect possibly mediated by the endothelin B receptor.

journal_name

Intensive Care Med

journal_title

Intensive care medicine

authors

Rossi P,Persson B,Boels PJ,Arner A,Weitzberg E,Oldner A

doi

10.1007/s00134-007-0980-9

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

873-80

issue

5

eissn

0342-4642

issn

1432-1238

journal_volume

34

pub_type

杂志文章

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