Effects of catecholamines on the pulmonary circulation in the ovine fetus

Jaillard, Sophie; Houfflin‐Debarge, V.; Riou, Yvon; Rakza, Thameur; Klosowski, S; Lequien, P; Storme, Laurent

doi:10.1152/ajpregu.2001.281.2.r607

Cited by 46 publications

(35 citation statements)

References 40 publications

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“…Finally, in our study, basal PVRs were in the same range as those measured in previous studies (17,32,33).…”

supporting

confidence: 87%

“…In vitro studies have reported that relaxant effects of norepinephrine observed in some systemic (15) and pulmonary (16) vessels in newborn animals result from endothelial ␣ 2 -adrenoceptor activation. Our in vivo studies further support the hypothesis that norepinephrine may activate ␣ 2 -adrenoceptors: 1) norepinephrine induces a potent pulmonary vasodilation in fetal lambs (17); 2) norepinephrineinduced pulmonary vasodilation is mediated by NO production (17); 3) selective ␣ 2 -adrenoceptor blockade abolishes the pulmonary vasodilator response to norepinephrine; and 4) the ␣ 2 -agonist UK 14,304 mimics the effects of norepinephrine on the pulmonary circulation. High circulating norepinephrine levels are found during fetal life (10,11).…”

supporting

confidence: 75%

“…Such changes in sympathetic outflow may modulate pulmonary vascular tone. However, our previous in vivo study does not support this hypothesis as norepinephrine reduces PVR in the fetal lamb (17). Third, changes in pulmonary vascular tone observed during norepinephrine or yohimbine infusion may result from systemic or centrally mediated reflex events.…”

mentioning

confidence: 76%

“…Although norepinephrine is commonly known as a vasopressor agent, in vitro studies have shown that norepinephrine dilates some systemic (15) and pulmonary (16) vessels in newborn animals. We reported that norepinephrine infusion induces a potent NO-dependent pulmonary vasodilation in fetal lambs (17). As ␣ 2 -adrenoceptor antagonists were found to inhibit norepinephrine-mediated relaxation of pulmonary (16,18) or systemic arteries (15), or enhance norepinephrine-mediated pulmonary vasoconstrictive response (8,9), norepinephrine-mediated pulmonary vasodilation may result from activation of endothelial ␣ 2 -adrenoceptors.…”

mentioning

confidence: 96%

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Role of the Alpha2-Adrenoceptors on the Pulmonary Circulation in the Ovine Fetus

et al. 2003

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Recent in vitro studies reported that nitric oxide release and pulmonary vasorelaxation can be mediated by endothelial ␣ 2 -adrenoceptor activation. As norepinephrine (␣ 1 -,␣ 2 -, and ␤ 1 -adrenoceptor agonist) was found to induce pulmonary vasodilation in the ovine fetus, we hypothesized that ␣ 2 -adrenoceptors may modulate basal pulmonary vascular tone and mediate the vascular effect of norepinephrine during fetal life. To determine the role of ␣ 2 -adrenoceptors and the mechanisms of norepinephrine-mediated vasodilation in the fetal pulmonary circulation, we tested, in chronically prepared late-gestation fetal lambs, the hemodynamic response to 1) yohimbine (␣ 2 antagonist); 2) UK 14,304 (␣ 2 agonist) with and without L-nitro-arginine (nitric oxide synthase inhibitor); and 3) norepinephrine infusion with and without yohimbine. We found that yohimbine increased mean pulmonary artery pressure by 15% (p Ͻ 0.05), decreased pulmonary flow by 22% (p Ͻ 0.01), and increased pulmonary vascular resistance by 51% (p Ͻ 0.01). UK 14,304 increased pulmonary flow by 145% (p Ͻ 0.01) and decreased pulmonary vascular resistance by 58% (p Ͻ 0.01). L-Nitro-arginine abolished the UK 14,304-mediated pulmonary vasodilation. Norepinephrine (0.5 g·kg Ϫ1 ·min Ϫ1 ) increased both pulmonary flow by 61% (p Ͻ 0.01) and pulmonary arterial pressure by 13% (p Ͻ 0.01) and decreased pulmonary vascular resistance by 33% (p Ͻ 0.01). Yohimbine abolished the norepinephrine-induced pulmonary vasodilation. This study suggests that 1) a basal ␣ 2 -adrenoceptor activation-induced pulmonary vasodilation exists during fetal life; 2) the pulmonary vascular effects of ␣ 2 -adrenoceptor activation are related at least in part to nitric oxide production; and 3) the norepinephrine-mediated pulmonary vasodilation involves ␣ 2 -adrenoceptor activation. As a surge of norepinephrine exists at birth, we speculate that norepinephrine and endothelial ␣ 2 -adrenoceptor activation may play a significant role in pulmonary vasodilation at birth. High resistance and low blood flow characterize the fetal pulmonary circulation. PVR decreases dramatically during the normal transition from the fetal to neonatal circulation at birth. Three main factors contribute to the increase of Q p during this transition: ventilation of the lung (1), increased O 2 (2), and hemodynamic forces, such as increased shear stress (3). Vasoactive mediators released from the endothelium, such as NO, play a major role in the regulation of acute changes in vascular tone in the perinatal lung, and in many cases, modulate the pulmonary vascular response to these birth-related stimuli (4). Inhibition of NO synthesis can attenuate the postnatal adaptation of the pulmonary circulation (5). The vasodilator action of several substances, such as acetylcholine, bradykinin, or ADP, and shear stress are dependent, at least in part, on NO release (6). More recently, in vitro studies reported that NO release and pulmonary vasorelaxation can also be mediated by endothelial ␣ 2 -adrenoceptor activation (7-9). Ho...

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“…Finally, in our study, basal PVRs were in the same range as those measured in previous studies (17,32,33).…”

supporting

confidence: 87%

supporting

confidence: 75%

mentioning

confidence: 76%

mentioning

confidence: 96%

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Role of the Alpha2-Adrenoceptors on the Pulmonary Circulation in the Ovine Fetus

et al. 2003

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“…Stress hormones have also been shown to modulate the pulmonary vascular tone and reactivity during the perinatal life (12,26,29). These data suggest that perinatal stress may alter the pulmonary circulation.…”

mentioning

confidence: 91%

Effects of nociceptive stimuli on the pulmonary circulation in the ovine fetus

Houfflin‐Debarge¹,

Delelis²,

Jaillard³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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The fetus is able to exhibit a stress response to painful events, and stress hormones have been shown to modulate pulmonary vascular tone. At birth, the increased level of stress hormones plays a significant role in the adaptation to postnatal life. We therefore hypothesized that pain may alter pulmonary circulation in the perinatal period. The hemodynamic response to subcutaneous injection of formalin, which is used in experimental studies as nociceptive stimulus, was evaluated in chronically prepared, fetal lambs. Fetal lambs were operated on at 128 days gestation. Catheters were placed into the ascending aorta, superior vena cava, and main pulmonary artery. An ultrasonic flow transducer was placed around the left pulmonary artery. Three subcutaneous catheters were placed in the lambs' limb. The hemodynamic responses to subcutaneous injection of formalin, to formalin after fetal analgesia by sufentanil, and to sufentanil alone were recorded. Cortisol and catecholamine concentrations were also measured. Pulmonary vascular resistances (PVR) increased by 42% (P Ͻ 0.0001) after formalin injection. Cortisol increased by 54% (P ϭ 0.05). During sufentanil infusion, PVR did not change significantly after formalin. Cortisol increased by 56% (P Ͻ 0.05). PVR did not change during sufentanil infusion. Norepinephrine levels did not change during any of the protocols. Our results indicate that nociceptive stimuli may increase the pulmonary vascular tone. This response is not mediated by an increase in circulating catecholamine levels. Analgesia prevents this effect. We speculate that this pulmonary vascular response to nociceptive stimulation may explain some hypoxemic events observed in newborn infants during painful intensive care procedures. experimental pain animal model; fetal pain; fetal analgesia; pulmonary vascular reactivity; stress hormones THE DEVELOPMENT OF FETAL INVASIVE procedures and a better knowledge about pain in preterm and full-term newborn infants have led to increased interest in the subject of fetal pain. Nociception during early development is poorly understood. However, numerous indirect evidence such as behavioral or neurohormonal responses to invasive procedures suggests that the fetus can feel pain very early in gestation (17,18,20). Fetal brain-sparing response has been observed after procedures involving transgression of fetal trunk from as early as 16 wk (54). Furthermore, transfusion through the intrahepatic veins is associated with substantial rises in stress hormones (norepinephrine, cortisol, ␤-endorphin) from as early as 18 wk of gestation (17,18).At birth, the increase in stress hormones plays a significant role in the adaptation to postnatal life, including increased left ventricular contractility, lung fluid reabsorption, and surfactant release (11,25,35,47,49,60). Stress hormones have also been shown to modulate the pulmonary vascular tone and reactivity during the perinatal life (12,26,29). These data suggest that perinatal stress may alter the pulmonary circulation. Furthermore, hyp...

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Dynamic relationships between catecholamine-induced shifts of pressure and blood flow in pulmonary artery

2008

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Experiments on cats showed that catecholamines produced maximum changes in pulmonary artery blood pressure during 12-16 sec postinjection, while blood flow in this artery attained maximum only to 40 sec postinjection, i.e. changes in blood flow attained maximum and ended later than blood pressure shifts. Intravenous epinephrine produced bidirectional changes in blood pressure, while norepinephrine always elevated blood pressure in the pulmonary artery; pulmonary circulation increased after injection of both catecholamines.

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Effects of catecholamines on the pulmonary circulation in the ovine fetus

Cited by 46 publications

References 40 publications

Role of the Alpha2-Adrenoceptors on the Pulmonary Circulation in the Ovine Fetus

Role of the Alpha2-Adrenoceptors on the Pulmonary Circulation in the Ovine Fetus

Effects of nociceptive stimuli on the pulmonary circulation in the ovine fetus

Dynamic relationships between catecholamine-induced shifts of pressure and blood flow in pulmonary artery

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