Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ

1991 ◽  
Vol 70 (3) ◽  
pp. 1228-1234 ◽  
Author(s):  
S. Cassin ◽  
V. Kristova ◽  
T. Davis ◽  
P. Kadowitz ◽  
G. Gause
Keyword(s):  
Pulmonary Circulation ◽  
Vena Cava ◽  
Fetal Lung ◽  
Left Pulmonary Artery ◽  
Pulmonary Vasculature ◽  
Fetal Sheep ◽  
Vascular Responses ◽  
Arterial Perfusion ◽  
Ovine Fetal

Pulmonary vascular responses to endothelin (ET-1), a peptide derived from endothelial cells in culture, were investigated in the ovine fetus delivered by cesarean section from chloralose-anesthetized ewes with intact umbilical circulation. Circulation to the lower left lobe of the fetal lung was isolated in situ and perfused at constant flow with blood withdrawn from the inferior vena cava. Injection of graded doses of ET-1 into the left pulmonary artery decreased pulmonary arterial perfusion pressure in a dose-related manner. At doses of 100, 300, and 1,000 ng, pulmonary vascular resistance per kilogram body weight (PVR/kg) was decreased 30, 40, and 42%, respectively. However, when fetuses were ventilated with 100% oxygen, 100- and 300-ng doses of ET-1 decreased PVR/kg by 5 and 9%, respectively. In contrast, injection of 1,000 ng of ET-1 resulted in a reversal of the response, and PVR/kg was increased by 70%. Ventilation of the right lung alone resulted in a similar reversal of the vasodilator response to 1,000 ng of ET-1, and a 138% increase in PVR/kg was recorded. These studies demonstrate for the first time that ET-1 has vasodilator activity in the normally high-tone ovine fetal pulmonary circulation. In addition, these results show that ET-1 has vasoconstrictor activity in the newly ventilated low-tone pulmonary vasculature. The present data indicate the pulmonary vascular responses to ET-1 are tone dependent in the ovine fetal pulmonary circulation.

Regulation of lactic acid production during exercise

1988 ◽  
Vol 65 (2) ◽  
pp. 509-518 ◽  
Author(s):  
A. Katz ◽  
K. Sahlin
Keyword(s):  
Lactic Acid ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Synergistic Effect ◽  
Lactic Acid Production ◽  
Fetal Lung ◽  
Lung Maturation ◽  
Fetal Sheep ◽  
Epidermal Growth ◽  
Ovine Fetal

Cortisol has minimal effects on lung maturation in fetal sheep before 130 days gestation. To test whether there is enhancement of cortisol action by other hormones, cortisol (F), triiodothyronine (T3), epinephrine (E), prolactin (PRL), and epidermal growth factor (EGF), alone or in combination, were infused into fetal sheep for 84 h between 124 and 128 days gestation. A mixture of F + T3 + PRL, but not any combination of two hormones, increased both distensibility [1.71 +/- 0.12 (SE) ml of air/g wet wt at 40 cmH2O, V40] and stability (1.16 +/- 0.09 ml of air per g wet wt at 5 cmH2O, V5) to near full-term values, above values resulting from treatment with F alone (0.91 +/- 0.12 and 0.43 +/- 0.09 ml/g, P less than 0.01). Only F had an effect when given alone, V40 increasing (P less than 0.05). Treatment with F + T3 (0.81 +/- 0.18 ml/g) and F + E (0.77 +/- 0.07 ml/g) increased V5 above values obtained with F alone (P less than 0.05). Alveolar saturated phosphatidylcholine (SPC) was higher after treatment with F + T3 (161 +/- 52 micrograms/g), F + T3 + PRL (156 +/- 53 micrograms/g, P less than 0.05), and F + E (113 +/- 40 micrograms/g, P = 0.07) than after F (12 +/- 3 micrograms/g). We conclude that F, T3, and PRL have a synergistic effect on the development of distensibility and stability of the ovine fetal lung.

Urocortin: a mechanism for the sustained activation of the HPA axis in the late-gestation ovine fetus?

2002 ◽  
Vol 283 (1) ◽  
pp. E165-E171 ◽  
Author(s):  
Alison C. Holloway ◽  
David C. Howe ◽  
Gabriel Chan ◽  
Vicki L. Clifton ◽  
Roger Smith ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Late Gestation ◽  
Pituitary Cells ◽  
Fetal Sheep ◽  
Antisense Probe ◽  
Pomc Mrna ◽  
Ovine Fetus ◽  
Ovine Fetal ◽  
Sustained Activation

We hypothesized that urocortin might be produced in the pituitary of the late-gestation ovine fetus in a manner that could contribute to the regulation of ACTH output. We used in situ hybridization and immunohistochemistry to identify urocortin mRNA and protein in late-gestation fetal pituitary tissue. Levels of urocortin mRNA rose during late gestation and were associated temporally with rising concentrations of pituitary proopiomelanocortin (POMC) mRNA. Urocortin was localized both to cells expressing ACTH and to non-ACTH cells by use of dual immunofluorescence histochemistry. Transfection of pituitary cultures with urocortin antisense probe reduced ACTH output, whereas added urocortin stimulated ACTH output from cultured pituitary cells. Cortisol infusion for 96 h in chronically catheterized late-gestation fetal sheep significantly stimulated levels of pituitary urocortin mRNA. We conclude that urocortin is expressed in the ovine fetal pituitary and localizes with, and can stimulate output of, ACTH. Regulation of urocortin by cortisol suggests a mechanism to override negative feedback and sustain feedforward of fetal hypothalamic-pituitary-adrenal function, leading to birth.

Inhibition of 20-HETE abolishes the myogenic response during NOS antagonism in the ovine fetal pulmonary circulation

2005 ◽  
Vol 289 (2) ◽  
pp. L261-L267 ◽  
Author(s):  
Thomas A. Parker ◽  
Theresa R. Grover ◽  
John P. Kinsella ◽  
John R. Falck ◽  
Steven H. Abman
Keyword(s):  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Pulmonary Circulation ◽  
Ductus Arteriosus ◽  
Combined Treatment ◽  
Specific Inhibitor ◽  
Fetal Lung ◽  
Myogenic Response ◽  
Fetal Sheep ◽  
Artery Pressure

Mechanisms that maintain high pulmonary vascular resistance (PVR) and oppose vasodilation in the fetal lung are poorly understood. In fetal lambs, increased pulmonary artery pressure evokes a potent vasoconstriction, suggesting that a myogenic response contributes to high PVR in the fetus. In adult systemic circulations, the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) has been shown to modulate the myogenic response, but its role in the fetal lung is unknown. We hypothesized that acute increases in pulmonary artery pressure release 20-HETE, which causes vasoconstriction, or a myogenic response, in the fetal lung. To address this hypothesis, we studied the hemodynamic effects of N-methylsufonyl-12,12-dibromododec-11-enamide (DDMS), a specific inhibitor of 20-HETE production, on the pulmonary vasoconstriction caused by acute compression of the ductus arteriosus (DA) in chronically prepared fetal sheep. An inflatable vascular occluder around the DA was used to increase pulmonary artery pressure under three study conditions: control, after pretreatment with nitro-l-arginine (l-NA; to inhibit shear-stress vasodilation), and after combined treatment with both l-NA and a specific 20-HETE inhibitor, DDMS. We found that DA compression after l-NA treatment increased PVR by 44 ± 12%. Although intrapulmonary DDMS infusion did not affect basal PVR, DDMS completely abolished the vasoconstrictor response to DA compression in the presence of l-NA (44 ± 12% vs. 2 ± 4% change in PVR, l-NA vs. l-NA + DDMS, P < 0.05). We conclude that 20-HETE mediates the myogenic response in the fetal pulmonary circulation and speculate that pharmacological inhibition of 20-HETE might have a therapeutic role in neonatal conditions characterized by pulmonary hypertension.

scholarly journals Fasudil inhibits the myogenic response in the fetal pulmonary circulation

2008 ◽  
Vol 295 (4) ◽  
pp. H1505-H1513 ◽  
Author(s):  
Pierre Tourneux ◽  
Marc Chester ◽  
Theresa Grover ◽  
Steven H. Abman
Keyword(s):  
Blood Flow ◽  
Pulmonary Circulation ◽  
Ductus Arteriosus ◽  
Fetal Lung ◽  
Late Gestation ◽  
Time Dependent ◽  
Myogenic Response ◽  
Rock Inhibitor ◽  
Fetal Sheep ◽  
Rock Activity

In addition to high pulmonary vascular resistance (PVR) and low pulmonary blood flow, the fetal pulmonary circulation is characterized by mechanisms that oppose vasodilation. Past work suggests that high myogenic tone contributes to high PVR and may contribute to autoregulation of blood flow in the fetal lung. Rho-kinase (ROCK) can mediate the myogenic response in the adult systemic circulation, but whether high ROCK activity contributes to the myogenic response and modulates time-dependent vasodilation in the developing lung circulation are unknown. We studied the effects of fasudil, a ROCK inhibitor, on the hemodynamic response during acute compression of the ductus arteriosus (DA) in chronically prepared, late-gestation fetal sheep. Acute DA compression simultaneously induces two opposing responses: 1) blood flow-induced vasodilation through increased shear stress that is mediated by NO release and 2) stretch-induced vasoconstriction (i.e., the myogenic response). The myogenic response was assessed during acute DA compression after treatment with Nω-nitro-l-arginine, an inhibitor of nitric oxide synthase, to block flow-induced vasodilation and unmask the myogenic response. Intrapulmonary fasudil infusion (100 μg over 10 min) did not enhance flow-induced vasodilation during brief DA compression but reduced the myogenic response by 90% ( P < 0.05). During prolonged DA compression, fasudil prevented the time-dependent decline in left pulmonary artery blood flow at 2 h (183 ± 29 vs. 110 ± 11 ml/min with and without fasudil, respectively; P < 0.001). We conclude that high ROCK activity opposes pulmonary vasodilation in utero and that the myogenic response maintains high PVR in the normal fetal lung through ROCK activation.

NO and prostaglandin interactions during hemodynamic stress in the fetal ovine pulmonary circulation

2001 ◽  
Vol 281 (5) ◽  
pp. L1157-L1163 ◽  
Author(s):  
Jeanne P. Zenge ◽  
Robyn L. Rairigh ◽  
Theresa R. Grover ◽  
Laurent Storme ◽  
Thomas A. Parker ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Circulation ◽  
Ductus Arteriosus ◽  
Fetal Lung ◽  
Left Pulmonary Artery ◽  
Saline Control ◽  
Hemodynamic Stress ◽  
Pulmonary Vasodilators ◽  
Cox Inhibitor ◽  
No Release

Nitric oxide (NO) and prostacyclin (PGI2) are potent fetal pulmonary vasodilators, but their relative roles and interactions in the regulation of the perinatal pulmonary circulation are poorly understood. We compared the separate and combined effects of nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibition during acute hemodynamic stress caused by brief mechanical compression of the ductus arteriosus (DA) in chronically prepared fetal lambs. Nitro-l-arginine (l-NNA; NOS antagonist), meclofenamate (Mec; COX inhibitor), combined drugs (l-NNA-Mec), or saline (control) was infused into the left pulmonary artery (LPA) before DA compression. In controls, DA compression decreased pulmonary vascular resistance (PVR) by 43% ( P < 0.01). l-NNA, but not Mec, treatment completely blocked vasodilation and caused a paradoxical increase in PVR (+31%; P < 0.05). The effects ofl-NNA-Mec and l-NNA on PVR were similar. To determine if the vasodilator effect of PGI2 is partly mediated by NO release, we studied PGI2-induced vasodilation before and after NOS inhibition. l-NNA treatment blocked the PGI2-induced rise in LPA blood flow by 73% ( P < 0.001). We conclude that NO has a greater role than PGs in fetal pulmonary vasoregulation during acute hemodynamic stress and that PGI2-induced pulmonary vasodilation is largely mediated by NO release in the fetal lung.

Pentobarbital attenuates pulmonary vasoconstriction in isolated sheep lungs

1989 ◽  
Vol 257 (3) ◽  
pp. H898-H903 ◽  
Author(s):  
R. C. Wetzel ◽  
L. D. Martin
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Effective Concentration ◽  
Pulmonary Vasculature ◽  
Vascular Response ◽  
Vascular Responses ◽  
Pulmonary Vasoconstriction ◽  
Wide Range ◽  
Instantaneous Pressure ◽  
Constrictor Response

Pentobarbital sodium is a widely used anesthetic agent that has been demonstrated to attenuate systemic vascular responses to multiple pressors. To determine whether pentobarbital affected pulmonary vasoreactivity we determined the pulmonary vascular response to hypoxia and potassium in isolated in situ perfused sheep lungs. The flow resistive characteristics of the pulmonary vasculature were assessed by determining mean instantaneous pressure-flow relationships over a wide range of flows (20–120 ml.min-1.kg body wt-1) with PIO2 of 200 and 30 Torr, with and without pentobarbital. Pentobarbital attenuated hypoxic pulmonary vasoconstriction (P less than 0.001) in a concentration-dependent fashion (50% effective concentration = 0.42 mM). In addition, the pulmonary constrictor response to potassium was markedly blunted by pentobarbital (P less than 0.001). We conclude that pentobarbital inhibits hypoxic pulmonary vasoconstriction in a concentration-dependent fashion and that this inhibition of pulmonary vasoconstriction in isolated sheep lungs is not specific for hypoxia.

Levels of pro-opiomelanocortin and prolactin mRNA in the fetal sheep pituitary following hypoxaemia and glucocorticoid treatment in late gestation

1995 ◽  
Vol 147 (1) ◽  
pp. 139-146 ◽  
Author(s):  
S G Matthews ◽  
J R G Challis
Keyword(s):  
Late Gestation ◽  
Pars Intermedia ◽  
Mrna Levels ◽  
Glucocorticoid Treatment ◽  
Fetal Sheep ◽  
Fetal Plasma ◽  
Pomc Mrna ◽  
Highly Sensitive ◽  
Ovine Fetal

Abstract It is well established that corticotrophin-releasing hormone and vasopressin can induce both synthesis and release of ACTH from the ovine pituitary gland, and that glucocorticoids can inhibit these responses. Changes in the abundance, localization and distribution of proopiomelanocortin (POMC) mRNA and prolactin (PRL) mRNA in the ovine fetal pituitary were examined by in situ hybridization following hypoxaemia applied in the presence or absence of concomitant cortisol in late gestation (day 135). Fetuses were distributed amongst four groups; saline-infused/normoxaemic, cortisol-infused/normoxaemic (0·3 mg/h), saline-infused/hypoxaemic and cortisol-infused/hypoxaemic. Hypoxaemia (6 h) was induced by reducing the maternal PaO2, resulting in a 6–8 mmHg decrease in fetal arterial PO2. Fetal infusions were commenced 5 h prior to and maintained throughout the treatment period. Hypoxaemia, which elevated fetal plasma ACTH and cortisol, caused a significant (P<0·05) increase in POMC mRNA in the pars distalis (PD), but was without effect on POMC mRNA in the pars intermedia (PI). Cortisol infusion attenuated the hypoxaemiainduced increase in POMC mRNA in the PD, but was without effect on non-stimulated steady-state POMC mRNA levels in either the PD or PI. PRL mRNA was only present in the PD and significantly (P<0·05) increased after cortisol infusion and hypoxaemia. In conclusion (i) POMC and PRL mRNA in the PD are increased following moderate hypoxaemia, (ii) cortisol attenuates changes in POMC mRNA but not PRL mRNA in the PD following hypoxaemia and (iii) cortisol increases PRL mRNA levels in the PD. Synthesis of POMC and PRL in the fetal PD is highly sensitive to homeostatic perturbations and glucocorticoids in late gestation. Journal of Endocrinology (1995) 147, 139–146

scholarly journals Expression of ENaC subunits, chloride channels, and aquaporins in ovine fetal lung: ontogeny of expression and effects of altered fetal cortisol concentrations

2009 ◽  
Vol 297 (2) ◽  
pp. R453-R461 ◽  
Author(s):  
Nathan M. Jesse ◽  
Jarret McCartney ◽  
Xiaodi Feng ◽  
Elaine M. Richards ◽  
Charles E. Wood ◽  
...  
Keyword(s):  
Ion Channels ◽  
Chloride Channels ◽  
Fetal Lung ◽  
Fluid Secretion ◽  
Late Gestation ◽  
Transmembrane Conductance Regulator ◽  
Ontogenetic Changes ◽  
Transmembrane Conductance ◽  
Fetal Sheep ◽  
Ovine Fetal

Transition of the epithelium of the fetal lung from fluid secretion to fluid reabsorption requires changes in the expression of ion channels. Corticosteroids regulate expression of several of these channels, including the epithelium sodium channel (ENaC) subunits and aquaporins (AQP). We investigated the ontogenetic changes in these ion channels in the ovine fetal lung during the last half of gestation, a time of increasing adrenal maturation. Expression of the mRNAs for the chloride channels, cystic fibrosis transmembrane conductance regulator (CFTR), and chloride channel 2 (CLCN2) decreased with age. Expression of mRNAs for AQP1, AQP5, and for subunits of ENaC (α, β, γ) increased with age. In the fetal sheep the expression of ENaCβ mRNA was dramatically higher than the expression of ENaCα or ENaCγ, but expression of ENaCβ protein decreased with maturation, although the ratio of the mature (112 kDa) to immature (102 kDa) ENaCβ protein increased with age, particularly in the membrane fraction. In contrast, ENaCα mRNA and protein both increase with maturation, and the mature form of ENaCα (68 kDa) predominates at all ages. A modest increase in fetal cortisol, within the range expected to occur naturally in late gestation but prior to active labor, increased ENaCα mRNA but not ENaCβ, ENaCγ, or AQP mRNAs. We conclude that in the ovine fetal lung, appearance of functional sodium channels is associated with induction of ENACα and ENaCγ, and that ENaCα expression may be induced by even small, preterm increases in fetal cortisol.

scholarly journals 13-week Pulmonary Sonoangiogram by 3D HDlive Flow

2015 ◽  
Vol 9 (4) ◽  
pp. 355-356
Author(s):  
Ritsuko K Pooh
Keyword(s):  
Umbilical Vein ◽  
Power Doppler ◽  
Vena Cava ◽  
Morphological Structure ◽  
Fetal Lung ◽  
First Trimester ◽  
Ductus Venosus ◽  
Pulmonary Vasculature ◽  
Congenital Cystic Adenomatoid Malformation ◽  
Lung Maturation

ABSTRACT Recent development of three-dimensional (3D)/four-dimensional (4D) sonography has revealed structural and functional early human development in utero and 3D/4D sonography moved prenatal diagnosis of fetal anomalies from the second to the first trimester of pregnancy. HDlive flow is a recent application of 3D ultrasound technology generating a 3D-view of the blood flow and providing a realistic rendering of fine vascular structure. Combination of HDlive silhouette and flow can be described as a ‘see-through fashion’, because of its comprehensive orientation and persuasive localization of inner structure as well as of fetal angiostructure inside the morphological structure. The picture of this month demonstrates normal intracorporeal angiostructure by 3D HDlive silhouette/flow imaging with bidirectional power Doppler at 13 weeks of gestation. The umbilical arteries, umbilical vein, ductus venosus, inferior vena cava, descending aorta as well as rich pulmonary vascularity are clearly demonstrated in a single 3D reconstructed image. This image indicates existence of rich pulmonary vascularity from even before lung maturation in the first trimester. Prenatal prediction of neonatal prognosis in cases with still remains a challenge but previous trials have been done after 20 weeks of gestation. Nowadays, many of pulmonary lesions, such as congenital diaphragmatic hernia (CDH) and congenital cystic adenomatoid malformation (CCAM), have been diagnosed in the first or early second trimesters. Recent advanced imaging technology of HDlive flow showing pulmonary vasculature from the first trimester in this article may have a great potential to investigate fetal lung development and maturity from early gestation and lead to scheduling of prenatal fetal treatment and proper management. How to cite this article Pooh RK. 13-week Pulmonary Sonoangiogram by 3D HDlive Flow. Donald School J Ultrasound Obstet Gynecol 2015;9(4):355-356.

Synergistic hormonal effects on lung maturation in fetal sheep

1988 ◽  
Vol 65 (1) ◽  
pp. 94-100 ◽  
Author(s):  
J. C. Schellenberg ◽  
G. C. Liggins ◽  
M. Manzai ◽  
J. A. Kitterman ◽  
C. C. Lee
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Synergistic Effect ◽  
Fetal Lung ◽  
Full Term ◽  
Lung Maturation ◽  
Fetal Sheep ◽  
Hormonal Effects ◽  
Epidermal Growth ◽  
Ovine Fetal

Cortisol has minimal effects on lung maturation in fetal sheep before 130 days gestation. To test whether there is enhancement of cortisol action by other hormones, cortisol (F), triiodothyronine (T3), epinephrine (E), prolactin (PRL), and epidermal growth factor (EGF), alone or in combination, were infused into fetal sheep for 84 h between 124 and 128 days gestation. A mixture of F + T3 + PRL, but not any combination of two hormones, increased both distensibility [1.71 +/- 0.12 (SE) ml of air/g wet wt at 40 cmH2O, V40] and stability (1.16 +/- 0.09 ml of air per g wet wt at 5 cmH2O, V5) to near full-term values, above values resulting from treatment with F alone (0.91 +/- 0.12 and 0.43 +/- 0.09 ml/g, P less than 0.01). Only F had an effect when given alone, V40 increasing (P less than 0.05). Treatment with F + T3 (0.81 +/- 0.18 ml/g) and F + E (0.77 +/- 0.07 ml/g) increased V5 above values obtained with F alone (P less than 0.05). Alveolar saturated phosphatidylcholine (SPC) was higher after treatment with F + T3 (161 +/- 52 micrograms/g), F + T3 + PRL (156 +/- 53 micrograms/g, P less than 0.05), and F + E (113 +/- 40 micrograms/g, P = 0.07) than after F (12 +/- 3 micrograms/g). We conclude that F, T3, and PRL have a synergistic effect on the development of distensibility and stability of the ovine fetal lung.

Sign in / Sign up

Export Citation Format

Share Document