Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia‐induced pulmonary vasoconstriction in a porcine model

Abstract

Dual endothelin receptor blockade during hypoxia attenuates the 'sustained' acute pulmonary vasoconstrictor response by reducing the mean pulmonary artery pressure increase by approx. 62% and by normalizing PVR. Pre-treatment with tezosentan before hypoxia, additionally attenuates the initial hypoxia-induced mean pulmonary artery pressure rise by approx. 70% and abolishes the PVR increase, during stable circulatory conditions, without affecting oxygenation.

Effects of simvastatin on pulmonary fibrosis, pulmonary hypertension and exercise capacity in bleomycin‐treated rats

“…Upregulation of the endothelin system has been documented in hypoxia‐induced pulmonary vasoconstriction, and endothelin receptor antagonists have been shown to attenuate this vasoconstriction (Hedelin et al . ). Moreover, Simvastatin reduces the TGF‐ß1‐stimulated endothelin‐1 release from human pulmonary artery smooth muscle cells (Ali et al .…”

“…Another modulator of hypoxic pulmonary vasoconstriction is cyclooxygenase‐derived thromboxane A 2 , a potent pulmonary vasoconstrictor. Cyclooxygenase‐2 inhibition and thromboxane A 2 receptor antagonism attenuate hypoxic pulmonary vasoconstriction in experimental animals (Kylhammar & Radegran ). Simvastatin has been shown to reduce the lipopolysaccharide (LPS)‐depended induction of prostaglandin E2, thromboxane A 2 synthesis and cyclooxygenase‐2 expression in human monocytic cells (Habib et al .…”

Cyclooxygenase‐2 inhibition and thromboxane A2 receptor antagonism attenuate hypoxic pulmonary vasoconstriction in a porcine model

“…, Hedelin et al . ), potentially may compensate when inhibiting COX‐2 or blocking the TXA 2 receptor. Using an in vivo model, though, the qualitative significance of selective COX‐2 inhibition with nimesulide and TXA 2 receptor blockade with daltroban in acute hypoxia‐induced PH was revealed.…”

The principal pathways involved in the in vivo modulation of hypoxic pulmonary vasoconstriction, pulmonary arterial remodelling and pulmonary hypertension

“…, Hedelin et al . ) as well as during 60‐min exposure to normobaric hypoxia or 3 days of hypobaric hypoxia at 4559 m, respectively, in humans (Modesti et al . , Faoro et al .…”