Inhalation of the ETA receptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction.

Inhalation of the ETA receptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction. Research Abstract Details 

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Inhalation of the ETA receptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction. Abstract Text:

Bodil Petersen,Maria Deja,Roland Bartholdy,Bernd Donaubauer,Sven Laudi,Roland C E Francis,Willehad Boemke,Udo Kaisers,Thilo Busch,Bodil Petersen,Maria Deja,Roland Bartholdy,Bernd Donaubauer,Sven Laudi,Roland C E Francis,Willehad Boemke,Udo Kaisers,Thilo Busch,

Endogenous endothelin (ET)-1 modulates hypoxic pulmonary vasoconstriction (HPV). Accordingly, intravenously applied ET(A) receptor antagonists reduce HPV, but this is accompanied by systemic vasodilation. We hypothesized that inhalation of an ET(A) receptor antagonist might act selectively on the pulmonary vasculature and investigated the effects of aerosolized LU-135252 in an experimental model of HPV. Sixteen piglets (weight: 25 +/- 1 kg) were anesthetized and mechanically ventilated at an inspiratory oxygen fraction (Fi(O(2))) of 0.3. After 1 h of hypoxia at Fi(O(2)) 0.15, animals were randomly assigned either to receive aerosolized LU-135252 as bolus (0.3 mg/kg for 20 min; n = 8, LU group), or to receive aerosolized saline (n = 8, controls). In all animals, hypoxia significantly increased mean pulmonary arterial pressure (32 +/- 1 vs. 23 +/- 1 mmHg; P < 0.01; means +/- SE) and increased arterial plasma ET-1 (0.52 +/- 0.04 vs. 0.37 +/- 0.05 fmol/ml; P < 0.01) compared with mild hyperoxia at Fi(O(2)) 0.3. Inhalation of LU-135252 induced a significant and sustained decrease in mean pulmonary arterial pressure compared with controls (LU group: 27 +/- 1 mmHg; controls: 32 +/- 1 mmHg; values at 4 h of hypoxia; P < 0.01). In parallel, mean systemic arterial pressure and cardiac output remained stable and were not significantly different from control values. Consequently, in our experimental model of HPV, the inhaled ET(A) receptor antagonist LU-135252 induced selective pulmonary vasodilation without adverse systemic hemodynamic effects.

Inhalation of the ETA receptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction. Publishing Authors By Initials

B Petersen,M Deja,R Bartholdy,B Donaubauer,S Laudi,RC Francis,W Boemke,U Kaisers,T Busch,B Petersen,M Deja,R Bartholdy,B Donaubauer,S Laudi,RC Francis,W Boemke,U Kaisers,T Busch,

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Inhalation of the ETA receptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: American journal of physiology. Regulatory, integr

VOLUME: 294

Page Numbers: R601-5

Journal Abbreviation: Am. J. Physiol. Regul. Integr.

ISSN: 0363-6119

DAY: 12

MONTH: 12

YEAR: 2007

Inhalation of the ETA receptor antagonist LU-135252 selectively attenuates hypoxic pulmonary vasoconstriction. Information

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LANGUAGE: eng

NlmUniqueID: 100901230

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AFFILIATION: Klinik und Poliklinik fuer Anaesthesiologie und Intensivtherapie, Universitaetsklinikum Leipzig, Liebigstr. 20 D-04103 Leipzig, Germany. udo.kaisers@medizin.uni-leipzig.de).

Country: United States

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MEDLINETA: Am J Physiol Regul Integr Comp

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