Role of veins in regulation of pulmonary circulation

Gao, Yuansheng; Raj, J. Usha

doi:10.1152/ajplung.00103.2004

Cited by 104 publications

(107 citation statements)

References 156 publications

(219 reference statements)

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“…This was demonstrated in the present study with endothelin-1, and in related studies using lung explants for histamine and serotonin [20,21]. In all these studies, pulmonary veins responded more strongly than pulmonary arteries, corroborating many other findings in rat, sheep and human lungs [29].…”

Section: Discussionsupporting

confidence: 92%

Characterisation of guinea pig precision-cut lung slices: comparison with human tissues

Ressmeyer

Larsson

Vollmer³

et al. 2006

Eur Respir J

155

169

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Precision-cut lung slices (PCLS) allow comparison of the airway responses of different species under identical experimental conditions. The aim of this study was to establish and characterise PCLS from guinea pigs (GPs) and to compare them with human PCLS.GP PCLS were prepared according to previously published procedures with the exception that the agarose solution and the initial incubation medium contained isoproterenol to avoid post mortem airway contraction.The median effective concentrations (EC50, expressed as nM) for agonist-induced bronchoconstriction in GP and human PCLS, respectively, were: leukotriene D 4 (1.8, 5.0); thromboxane (16, 1.3); serotonin (69, unresponsive); histamine (217, 2,170); and methacholine (231, 234). Allergen-induced bronchoconstriction of passively sensitised PCLS was attenuated by histamine or thromboxane-prostanoid receptor antagonists and was almost completely prevented by their combination with leukotriene receptor antagonists. Airways pre-contracted with methacholine were relaxed by the b-agonist salbutamol or the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. Simultaneous studies of airways and vessels are possible with, for example, EC50 values for endothelin-1 of 37 nM (pulmonary arteries), 10 nM (pulmonary veins) and 9.6 nM (airway).When compared with previous findings in rat and mouse, these data show that guinea pig lungs are a more appropriate model for human airway pharmacology than lungs from rats or mice.

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Section: Discussionsupporting

confidence: 92%

Characterisation of guinea pig precision-cut lung slices: comparison with human tissues

Ressmeyer

Larsson

Vollmer³

et al. 2006

Eur Respir J

155

169

View full text Add to dashboard Cite

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“…Arrigoni and colleagues (1) observed that the relaxation in response to acetylcholine, which also occurs by release of nitric oxide from the endothelium, was greater in 14-day-old porcine pulmonary veins compared with fetal veins. Similarly, Gao and Raj (9) found that acetylcholine is 10-fold more potent in relaxing pulmonary veins of newborn than fetal lambs. The postnatal increase in relaxation response we observed may thus be due to an increase in available nitric oxide from the endothelium after birth (2) as well as the increase in ET-B receptor density previously described (16,23).…”

Section: Discussionmentioning

confidence: 83%

Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung

Schindler

Hislop²,

Haworth³

2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Schindler MB, Hislop AA, Haworth SG. Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung. Am J Physiol Lung Cell Mol Physiol 292: L1273-L1279, 2007. First published January 26, 2007; doi:10.1152/ajplung.00173.2006.-The response of pulmonary arteries to endothelin-1 (ET-1) changes with age in normal pigs and is abnormal in pulmonary hypertension. The purpose of this study was to determine if the same is true of the pulmonary veins. We studied the wall structure and functional response to ET-1 in pulmonary veins from normal pigs from fetal life to adulthood and from pigs subjected to chronic hypobaric hypoxia either from birth for 3 days or from 3 to 6 days of age. In isolated normal veins, the contractile response decreased by 40% between late fetal life and 14 days of age with a concomitant twofold increase in endothelium-dependent relaxant response. The ET A antagonist BQ-123 reduced the contractile response significantly more in newborn than older animals, whereas the ET-B antagonist BQ-788 had no effect in fetal animals and maximally increased contraction at 14 days of age. Hypoxic exposure significantly increased pulmonary vein smooth muscle area and contractile response to ET-1. The relaxation response was impaired following hypoxic exposure from birth but not from 3 to 6 days of age. The ET A antagonist BQ-123 decreased contractile and increased dilator responses significantly more than in age-matched controls. Thus pulmonary veins show age-related changes similar to those seen in the pulmonary arteries with a decrease in ETA-mediated contractile and increase in ET-B-mediated relaxant response with age. Contractile response was also increased in hypoxia as in the arteries. This study suggests that pulmonary veins are involved in postnatal adaptation and the pathogenesis of pulmonary hypertension. postnatal adaptation; pulmonary hypertension A NUMBER OF ANIMAL AND HUMAN studies suggest a role for endothelin-1 (ET-1) in adaptation to extrauterine life (8,21) and in the pathogenesis of pulmonary hypertension (18). Endo et al. (8) found plasma ET-1 concentrations to be threefold higher at birth compared with 5 or 30 days in healthy human neonates, and similar changes have been described in piglets (21). ET-1 blood levels are elevated in patients with pulmonary hypertension and decrease following resolution in persistent pulmonary hypertension of the newborn (24), pulmonary hypertension due to congenital heart disease (18), and pulmonary hypertension due to acute lung injury (19).Experimental studies have shown that the contractile response to ET-1 decreases with increasing age in rabbit pulmonary arteries (7). The effect of age on the pharmacological responses of the porcine pulmonary veins to ET-1 has not been reported; however, as the threshold for ET-1-induced contraction is lower in pulmonary veins than in pulmonary arteries in the fetal lamb (29) and human (4), it is likely that the veins may also exhibit developmental changes in response to ET-1.In h...

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“…We have previously shown that a 30-min exposure to 100% O 2 significantly increases fifth-generation pulmonary arterial contractility in vitro to norepinephrine and potassium chloride compared with 21% O 2 (14). We speculate that we could not replicate this finding in vivo because of a) use of a different vasoconstrictor agent (thromboxane analog, U46619 instead of norepinephrine and potassium chloride); b) a higher degree of biologic variability in the intact lamb model, including the complex contribution of pulmonary arteries, arterioles and veins to PVR in the intact lung and lamb (23); and c) measurement at different points in time (24 h in our previous study versus 2-3 h in the current study). For instance, it is possible that a change in gene expression may require a longer interval to manifest as increased contractility.…”

Section: Discussionmentioning

confidence: 83%

Pulmonary Hemodynamics in Neonatal Lambs Resuscitated with 21%, 50%, and 100% Oxygen

et al. 2007

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ABSTRACT:The effect of resuscitation with varying levels of O 2 on pulmonary hemodynamics at birth is not well known. We hypothesized that the decrease in pulmonary vascular resistance (PVR) and subsequent response to pulmonary vasoconstrictors and vasodilators will differ following resuscitation with 21%, 50%, or 100%O 2 for 30 min at birth in normal term lambs. Lambs at 141 d gestation were delivered by cesarean section and ventilated with 21% (21% Res; n ϭ 6), 50% (50% Res; n ϭ 6), or 100% O 2 (100% Res; n ϭ 7) for 30 min followed by ventilation with 21% O 2 in all three groups. A greater decrease in PVR was seen with 50% and 100% O 2 ventilation than with 21% O 2 (0.21 Ϯ 0.02, 0.21 Ϯ 0.02, and 0.34 Ϯ 0.05 mm Hg/mL/min/kg, respectively). Subsequent pulmonary vasoconstriction to hypoxia (10% O 2 ) and the thromboxane analog U46619 (0.5 and 1 g/kg/min) was similar in all three groups. After inducing a stable elevation in PVR with U46619, impaired pulmonary vasodilation to inhaled NO (59 Ϯ 4, 65 Ϯ 4, and 74 Ϯ 5% of baseline PVR with 21, 50, and 100%Res, respectively) and acetylcholine infusion (67 Ϯ 8, 75 Ϯ 6, and 87 Ϯ 4% of baseline PVR with 21, 50, and 100%Res, respectively) and rebound pulmonary hypertension following their withdrawal were observed in the 100%Res group. We conclude that, while ventilation with 100% O 2 at birth results in a greater initial decrease in PVR, subsequent pulmonary vasodilation to NO/acetylcholine is impaired. (Pediatr Res 62: 313-318, 2007) F etal pulmonary vascular resistance is high and O 2 plays a crucial role in mediating the pulmonary vascular transition at birth (1). However, the optimal level of O 2 supplementation during resuscitation of a newborn infant remains controversial (2) despite publication of new guidelines (3). During resuscitation of a depressed newborn infant with potentially high PVR, there is concern that room air resuscitation may result in inadequate pulmonary vasodilation. It has been suggested that breathing 100% O 2 dilates constricted pulmonary arteries more efficiently than room air.Previous studies have demonstrated conflicting results regarding the effect of ventilation with different gas mixtures on PVR. Some studies indicate that ventilation with nitrogen, air, and O 2 are similarly effective in reducing fetal PVR in lambs (4,5). Other studies indicate that PVR drops more effectively with 100% O 2 (6) or air (7,8) than with a nitrogen-rich gas. It may be important to find an intermediate level of O 2 that has the advantages of short-term reduction in PVR without the toxicity of 100% O 2 (9,10). Recent studies examined pulmonary hemodynamic responses to 21% or 100% O 2 ventilation, but were conducted on hypoxemic lambs only after 12-72 h of age, after PVR had dropped from high fetal levels immediately after birth (11)(12)(13). Understanding the precise pulmonary hemodynamic response to ventilation with room air, 100% O 2 , and an intermediate level of O 2 exposure (such as 50% O 2 ) in animals at birth is vital for determining the safest protocol ...

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Role of veins in regulation of pulmonary circulation

Cited by 104 publications

References 156 publications

Characterisation of guinea pig precision-cut lung slices: comparison with human tissues

Characterisation of guinea pig precision-cut lung slices: comparison with human tissues

Postnatal changes in pulmonary vein responses to endothelin-1 in the normal and chronically hypoxic lung

Pulmonary Hemodynamics in Neonatal Lambs Resuscitated with 21%, 50%, and 100% Oxygen

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