Endothelin Dilates Bovine Pulmonary Circulation and Reverses Hypoxic Pulmonary Vasoconstriction

Deleuze, Philippe; Adnot, Serge; Shiiya, N; Thoraval, F. Roudot; Eddahibi, Saadia; Braquet, P.; Chabrier, Pierre‐Etienne; Loisance, D

doi:10.1097/00005344-199203000-00008

Cited by 34 publications

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“…Conversely, other investigators have found endothelin-1 antagonists to be without effect on HPV (19,36). Moreover, exogenous endothelin-1 or endothelin-3 have been shown to attenuate HPV when added during an acute hypoxic challenge (7,12). In the present study, endothelin-1 did not appear to be the endothelium-derived constrictor factor involved in phase II, since combined blockade of ET A and ET B receptors was without effect on HPV.…”

Section: Discussioncontrasting

confidence: 73%

Ca²⁺ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Robertson

Aaronson

Ward

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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Robertson, Tom P., Philip I. Aaronson, and Jeremy P. T. Ward. Ca 2ϩ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent. Am J Physiol Lung Cell Mol Physiol 284: L1121-L1126, 2003. First published February 28, 2003 10.1152/ajplung.00422. 2002The main aim of this study was to determine the effects of endothelium removal on tension and intracellular Ca 2ϩ ([Ca 2ϩ ]i) during hypoxic pulmonary vasoconstriction (HPV) in rat isolated intrapulmonary arteries (IPA). Rat IPA and mesenteric arteries (MA) were mounted on myographs and loaded with the Ca 2ϩ -sensitive fluorophore fura PE-3. Arteries were precontracted with prostaglandin F 2␣, and the effects of hypoxia were examined. HPV in isolated IPA consisted of a transient constriction superimposed on a second sustained phase. Only the latter phase was abolished by endothelial denudation. However, removal of the endothelium had no effect on [Ca 2ϩ ]i at any point during HPV. The endothelin-1 antagonists BQ-123 and BQ-788 did not affect HPV, although constriction induced by 100 nM endothelin-1 was abolished. In MA, hypoxia induced an initial transient rise in tension and [Ca 2ϩ ]i, followed by vasodilatation and a fall in [Ca 2ϩ ]i to (but not below) prehypoxic levels. These results are consistent with sustained HPV being mediated by an endothelium-derived constrictor factor that is distinct from endothelin-1 and that elicits vasoconstriction via Ca 2ϩ sensitization. pulmonary circulation; arteries; hypoxia THE MECHANISM(S) UNDERLYING hypoxic pulmonary vasoconstriction (HPV), a unique and vital homeostatic mechanism that matches ventilation to perfusion in the event of localized alveolar hypoxia (32), remain unresolved. Because HPV can be observed in isolated pulmonary arteries (8,10,18,22,24,25), the oxygen sensor and subsequent constrictor mechanism(s) must reside in either the smooth muscle, endothelium, or both. In rat intrapulmonary arteries (IPA), the response to acute hypoxia, usually in the presence of a small degree of agonist-induced tone, is biphasic in nature (9,10,18,19,(22)(23)(24)(25)(26), consisting of an initial transient rise in tension (phase I) superimposed on a more slowly developing sustained constriction (phase II). Under similar experimental conditions, an almost identical transient phase I constriction has been observed in a variety of isolated systemic arteries (6, 22, 37), whereas the second phase of the response in systemic arteries to hypoxia is vasodilatation (22). Because the phase II constriction is peculiar to pulmonary arteries, we have argued that phase II is the more physiologically important process for sustained HPV (2, 33). In support of this contention, we have reported that the selective Rho kinase antagonist Y-27632 inhibited the hypoxic pressor response in perfused rat lungs yet only inhibited the second phase of HPV in rat isolated arteries (25).We have reported that the sustained phase II constriction of HPV is endothelium dependent (22). This is in agreement with other reports th...

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Section: Discussioncontrasting

confidence: 73%

Ca²⁺ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Robertson

Aaronson

Ward

2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…It seems likely from experiments in a range of mammalian species that the differences in alveolar PCO 2 (P A CO 2 ) that are seen in different parts of the healthy human lung (3-6 kPa) are capable of inducing substantial differences in regional perfusion in both healthy and diseased lungs. In contrast, HPV is usually regarded as being largely inoperative until alveolar PO 2 (P A O 2 ) falls to values (~8 kPa) well below those seen in healthy human lungs at sea level (11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Pulmonary Vascular Response To Respiratory Gasesmentioning

confidence: 99%

Human pulmonary vascular responses to hypoxia and hypercapnia

Dorrington¹,

Talbot²

2004

Pflugers Arch - Eur J Physiol

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The ability of alveolar gas composition to influence pulmonary vascular tone has been appreciated for over 50 years. In particular, it has been proposed that both O2 and CO2 could play a role in the matching of perfusion to ventilation within the lung, improving the overall efficiency of gas exchange. A wide variety of experimental approaches has been used to investigate pulmonary vascular effects of the respiratory gases in a range of mammalian species. In this article, we review experiments performed in healthy humans, identify particular difficulties in the interpretation of such experiments, and discuss possible approaches to future study.

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“…The short-lived increase in PA P is in contrast to the sustained contractions observed in our in vitro studies of isolated equine pulmonary arteries (Benamou 1999) and d i fferent to the response to infusion (as opposed to bolus) administration of E T-1 in vivo (Deleuze et al 1992;Holm 1997;Ivy et al 1 9 9 6 ) . In these latter studies, ET-1 displayed the same sustained eff e c t on the pulmonary vascular bed as it did on the systemic vascular bed.…”

Section: Discussionmentioning

confidence: 62%

Equine pulmonary and systemic haemodynamic responses to endothelin‐1 and a selective ET_A receptor antagonist

Benamou

Marlin

Lekeux

2001

Equine Veterinary Journal

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Summary Based on previous in vitro studies, we hypothesised that endothelin (ET) would induce vasoconstriction in the pulmonary circululation of the horse and that this action would be mediated via ETA receptors. Pulmonary and systemic haemodynamic responses to endothelin‐1 (ET‐1), a potent vasoactive endogenous peptide, were investigated in 6 conscious, nonsedated horses at rest. Bolus i.v. injections of exogenous ET‐1 (0.1, 0.2 and 0.4 μg/kg bwt) caused significant increases in pulmonary (PAP) and carotid (CAP) artery pressures, with peak increases of 79% and 51% for mean PAP and CAP, respectively. The effect of ET‐1 on PAP and CAP was rapid and transient for PAP (∼10 min) but prolonged for CAP (up to 60 min). ET‐1 significantly decreased cardiac output by up to 35% and significantly increased systemic vascular resistance (SVR) by up to 104%. Pulmonary vascular resistance (PVR) showed a trend (P>0.05) to increase with 0.2 and 0.4 μg/kg bwt ET‐1. Infusion of a selective ETA receptor antagonist (TBC11251) completely inhibited the responses to a subsequent bolus of 0.2 μg/kg bwt ET‐1. We conclude that exogenous ET‐1 exerts a potent vasoconstrictive action on the pulmonary and systemic circulations of the horse. These effects appear to be mediated largely through ETA receptors in both circulations. Endothelin may play a role in hypertensive conditions in the horse.

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Endothelin Dilates Bovine Pulmonary Circulation and Reverses Hypoxic Pulmonary Vasoconstriction

Cited by 34 publications

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Ca²⁺ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Ca²⁺ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Human pulmonary vascular responses to hypoxia and hypercapnia

Equine pulmonary and systemic haemodynamic responses to endothelin‐1 and a selective ET_A receptor antagonist

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Endothelin Dilates Bovine Pulmonary Circulation and Reverses Hypoxic Pulmonary Vasoconstriction

Cited by 34 publications

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Ca2+ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Ca2+ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Human pulmonary vascular responses to hypoxia and hypercapnia

Equine pulmonary and systemic haemodynamic responses to endothelin‐1 and a selective ETA receptor antagonist

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Ca²⁺ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Ca²⁺ sensitization during sustained hypoxic pulmonary vasoconstriction is endothelium dependent

Equine pulmonary and systemic haemodynamic responses to endothelin‐1 and a selective ET_A receptor antagonist