Role of endothelins and nitric oxide in the pulmonary circulation of perinatal lambs during hyperoxia and hypoxia.

Abstract

Endothelins (ET) have opposite vascular effects mediated through different receptors: ET(A) receptors mediating vasoconstriction and ET(B) receptors mediating vasoconstriction as well as vasodilation. The role of ET in acute hypoxic pulmonary vasoconstriction (HPV) was studied after dual ET receptor blockade with bosentan and nitric oxide (NO) synthase inhibition with nitro-L-arginine (L-NA). We started from the hypothesis that ET antagonism may inhibit HPV but, if not, would do so after NO synthase inhibition. HPV was evaluated in anesthetized lambs, with an intact pulmonary circulation, by the increase in the mean pulmonary artery pressure (Ppa) minus occluded Ppa (Ppao) gradient in response to hypoxia (inspiratory oxygen fraction of 0.1) at different levels of pulmonary flow (multipoint pressure/flow relationships). ET receptor antagonism decreased pulmonary and systemic vascular tone both in hyperoxia and hypoxia. ET antagonism had no effect on HPV. NO synthase inhibition increased pulmonary vascular tone more in hypoxia than in hyperoxia so that HPV was enhanced. After L-NA, bosentan still decreased pulmonary vascular tone in hypoxia but did not affect the magnitude of HPV. The present results suggest that ET and NO are involved in the regulation of basal pulmonary vascular tone. Furthermore, the vasodilator effect of bosentan persisted in the presence of NO synthase inhibition, suggesting a non NO-dependent vasodilator mechanism. The results from these experiments are in agreement with the idea that ET do not play a major role in HPV in the perinatal lamb, even when it is enhanced by NO synthase inhibition.

• Authors: Dominique Biarent, Ives Hubloue, Gilbert Bejjani, Christian Mélot, Pascale Jespers, Robert Naeije, Marc Leeman
• Journal: Pediatric research (Pediatr Res) Vol. 59 Issue 1 Pg. 131-6 (Jan 2006) ISSN: 0031-3998 [Print] United States
• PMID: 16327012 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin Receptor Antagonists
• Endothelins
• Sulfonamides
• Nitroarginine
• Nitric Oxide
• Nitric Oxide Synthase
• Bosentan

Topics

• Animals
• Animals, Newborn
• Blood Pressure
• Bosentan
• Constriction, Pathologic (physiopathology)
• Dilatation, Pathologic (physiopathology)
• Endothelin Receptor Antagonists
• Endothelins (physiology)
• Hyperoxia (physiopathology)
• Hypoxia (physiopathology)
• Nitric Oxide (physiology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitroarginine (pharmacology)
• Pulmonary Artery (drug effects, physiopathology)
• Pulmonary Circulation (drug effects)
• Sheep, Domestic
• Sulfonamides (pharmacology)
• Vascular Resistance (drug effects)