Urapidil, but not dihydropyridine calcium channel inhibitors, preserves the hypoxic pulmonary vasoconstriction: an experimental study in pig arteries.

Fiche publication

Date publication

février 2019

Journal

Fundamental & clinical pharmacology

Auteurs

Membres identifiés du Cancéropôle Est :
Pr SCHINI-KERTH Valérie , Dr AUGER Cyril

Tous les auteurs :
Bopp C, Auger C, Mebazaa A, Joshi GP, Schini-Kerth VB, Diemunsch P

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/30811659

Résumé

Hypoxic pulmonary vasoconstriction (HPV) is a protective mechanism maintaining blood oxygenation by redirecting blood flow from poorly ventilated to well-ventilated areas in the lung. Such a beneficial effect is blunted by antihypertensive treatment with dihydropyridine calcium channel inhibitors. The aim of the present study was to evaluate the effect of urapidil, an antihypertensive agent acting as an α adrenergic antagonist and a partial 5-HT agonist, on HPV in porcine proximal and distal pulmonary artery rings, and to characterize underlying mechanisms. Rings from proximal and distal porcine pulmonary artery were suspended in organ chambers and aerated with a 95% O + 5% CO gas mixture. HPV was induced by changing the gas to a 95% N + 5% CO mixture following a low level of pre-contraction with U46619. Hypoxia induced a contractile response in both proximal and distal pulmonary artery rings. This effect is observed in the presence of a functional endothelium and is inhibited by a soluble guanylyl cyclase inhibitor (ODQ), a NO scavenger (carboxy-PTIO), and by catalase in proximal pulmonary artery rings. The endothelium-dependent HPV is prevented by nicardipine and clevidipine but remained unaffected by urapidil in both proximal and distal pulmonary artery rings. These findings indicate that urapidil, in contrast to nicardipine and clevidipine, preserves the hypoxia-triggered vasoconstriction in isolated pulmonary arteries. They further indicate the involvement of the NO-guanylyl cyclase pathway and H O in HPV. Further research is warranted to determine the potential clinical relevance of the preserved hypoxia-induced pulmonary vasoconstriction by urapidil.