Endothelin-1 release from lamb ductus arteriosus; relevance to postnatal closure of the vessel

1991 ◽  
Vol 69 (2) ◽  
pp. 218-221 ◽  
Author(s):  
Flavio Coceani ◽  
Lois Kelsey
Keyword(s):  
Key Words ◽  
Conformational Change ◽  
Contractile Response ◽  
Ductus Arteriosus ◽  
Endothelin 1 ◽  
Wet Weight ◽  
Presence And Absence ◽  
Near Term ◽  
Cytochrome P 450 ◽  
Postnatal Closure

Our previous investigations have shown that endothelin-1 (ET-1) is a singularly potent constrictor of the ductus arteriosus and that a cytochrome P-450 system located in the sarcolemma is crucial for the contractile response of the vessel to oxygen. We have now studied the release of ET-1 from isolated ductus arteriosus preparations of near-term fetal lambs. Preparations produced measurable amounts of ET-1 under basal conditions (about 0.04 pg/100 mg wet weight∙min) both in the presence and absence of the endothelium. Anisomycin (10−4 M) reduced this release by 50%, while thrombin (1 U/mL) doubled the release. Treatment with a CO mixture (CO/O2 ratio, 0.27) inhibited ET-1 release from intact and endothelium-denuded preparations. We propose that oxygen triggers closure of the ductus arteriosus at birth by causing a conformational change in a specific cytochrome P-450, which, in turn, provides the signal for the synthesis of the constrictor ET-1.Key words: ductus arteriosus closure, oxygen, cytochrome P-450, endothelin.

Involvement of intramural prostaglandin E2 in prenatal patency of the lamb ductus arteriosus

1986 ◽  
Vol 64 (6) ◽  
pp. 737-744 ◽  
Author(s):  
Flavio Coceani ◽  
Dayle Huhtanen ◽  
Nancy C. Hamilton ◽  
Isis Bishai ◽  
Peter M. Olley
Keyword(s):  
Release Rate ◽  
Enzyme System ◽  
Reduced Glutathione ◽  
Ductus Arteriosus ◽  
Prostaglandin E ◽  
Concomitant Treatment ◽  
Contractile State ◽  
Wet Weight ◽  
Near Term

Release of prostaglandin E2 (PGE2) was studied in isolated ductus arteriosus preparations from immature (103 or 104 days gestation; term, 147 days) and near-term fetal lambs. Mature preparations produced measurable amounts of the compound in most cases and the release rate was 19 ± 2 pg/(100 mg wet weight∙min) at a [Formula: see text] of 3–8 Torr (1 Torr = 133.3 Pa). PGE2 release increased with the [Formula: see text] of the medium, peak values (about 125 pg/(100 mg∙min)) being attained at 106–276 Torr when the oxygen-induced contraction was still submaximal. Experiments in which tissues were either contracted with excess potassium or relaxed with CO proved that PGE2 formation is independent from the contractile state. PGE2 was also released from ductus preparations lacking the adventitia, the intima, or both; however, release values were maximal when the adventitia was preserved. The magnitude of the intrinsic tone in these stripped preparations was inversely related to the rate of PGE2 formation. Reduced glutathione increased PGE2 release from the mature ductus, whole or stripped, and also relaxed hypoxic preparations; both effects were reversed by concomitant treatment with indomethacin. PGE2 synthesis tended to be greater in the immature than the mature ductus, maximal values (115 ± 27 pg/(100 mg∙min)) being observed at 6–8 Torr. We conclude that the ductus arteriosus is endowed with an enzyme system for the synthesis of PGE2 whose function accords with an effector role of the compound in the regulation of tone. These findings, together with the potent relaxation exerted by PGE2 at low [Formula: see text], indicate that the locally generated prostaglandin is well suited for keeping the ductus patent in the fetus.

Endothelin is a potent constrictor of the lamb ductus arteriosus

1989 ◽  
Vol 67 (8) ◽  
pp. 902-904 ◽  
Author(s):  
Flavio Coceani ◽  
Craig Armstrong ◽  
Lois Kelsey
Keyword(s):  
Contractile Response ◽  
Ductus Arteriosus ◽  
Extended Period ◽  
Cytochrome P 450

Endothelin was tested on isolated ductus arteriosus preparations from mature fetal Iambs. At low [Formula: see text] (18–24 Torr; 1 Torr = 133.3 Pa), the compound constricted the vessel dose-dependently over the range from about 10−10 to 10−7 M. The contraction was sustained and did not subside even after an extended period of washing. Endothelin was also effective on tissues ([Formula: see text], 217–231 Torr; indomethacin, 2.8 × 10−6 M) that had been completely relaxed with CO (CO/O2 ratio, 0.28). CO treatment interferes with a cytochrome P-450 mechanism, which is considered crucial for the contractile response of the vessel to oxygen. These findings are consistent with a role of endothelin in the closure of the ductus arteriosus at birth.Key words: ductus arteriosus closure, oxygen, cytochrome P-450.

Evidence for an effector role of endothelin in closure of the ductus arteriosus at birth

1992 ◽  
Vol 70 (7) ◽  
pp. 1061-1064 ◽  
Author(s):  
Flavio Coceani ◽  
Lois Kelsey ◽  
Eric Seidlitz
Keyword(s):  
Oxygen Concentration ◽  
Oxygen Tension ◽  
Ductus Arteriosus ◽  
Critical Role ◽  
Blood Oxygen ◽  
Endothelin 1 ◽  
A Value ◽  
Near Term ◽  
Oxygen Concentrations

The ductus arteriosus is a special muscular shunt that in the fetus allows blood to bypass the unexpanded lungs. It closes rapidly after birth and this event is initiated by the physiologic rise in blood oxygen tension. Endothelin-1 has been proposed by us as a local mediator for oxygen after demonstrating that it is formed within the ductus and is a potent ductus constrictor. To confirm this possibility, we have now measured the release of endothelin-1 from the isolated ductus of near-term fetal lambs at different oxygen concentrations of the medium. In addition, using the same preparation, we have examined the effect on contractile tone of compounds interfering with the synthesis (phosphoramidon, 50 μM) and action (BQ123, 1 μM) of endothelin-1. We report that release of endothelin-1 from the ductus tends to increase with the oxygen concentration up to a value mimicking the neonatal condition. Phosphoramidon and, to a greater degree, BQ123 inhibit the contraction of the vessel to oxygen. These results implicate endothelin-1 as the effector agent for oxygen in the ductus and, by extension, assign to this peptide a critical role in the closure of the vessel at birth.Key words: ductus arteriosus closure, oxygen, endothelin.

Factors that increase the contractile tone of the ductus arteriosus also regulate its anatomic remodeling

2001 ◽  
Vol 281 (1) ◽  
pp. R291-R301 ◽  
Author(s):  
Hiroki Kajino ◽  
Yao-Qi Chen ◽  
Steven R. Seidner ◽  
Nahid Waleh ◽  
Françoise Mauray ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vessel Wall ◽  
Contractile Response ◽  
Ductus Arteriosus ◽  
Inhibitory Effects ◽  
Additional Increase ◽  
Endogenous Prostaglandins ◽  
Near Term ◽  
Necessary And Sufficient ◽  
Preterm Newborns

Permanent closure of the full-term newborn ductus arteriosus (DA) occurs only if profound hypoxia develops within the vessel wall during luminal obliteration. We used fetal and newborn baboons and lambs to determine why the immature DA fails to remodel after birth. When preterm newborns were kept in a normoxic range (PaO2 : 50–90 mmHg), 86% still had a small patent DA on the sixth day after birth; in addition, the preterm DA wall was only mildly hypoxic and had only minimal remodeling. The postnatal increase in PaO2 normally induces isometric contractile responses in rings of DA; however, the excessive inhibitory effects of endogenous prostaglandins and nitric oxide, coupled with a weaker intrinsic DA tone, make the preterm DA appear to have a smaller increment in tension in response to oxygen than the DA near term. We found that oxygen concentrations, beyond the normoxic range, produce an additional increase in tension in the preterm DA that is similar to the contractile response normally seen at term. We predicted that preterm newborns, kept at a higher PaO2 , would have increased DA tone and would be more likely to obliterate their lumen. We found that preterm newborns, maintained at a PaO2 >200 mmHg, had only a 14% incidence of patent DA. Even though DA constriction was due to elevated PaO2 , obliteration of the lumen produced profound hypoxia of the DA wall and the same features of remodeling that were observed at term. DA wall hypoxia appears to be both necessary and sufficient to produce anatomic remodeling in preterm newborns.

Cytochrome P 450-linked monooxygenase: involvement in the lamb ductus arteriosus

1984 ◽  
Vol 246 (4) ◽  
pp. H640-H643 ◽  
Author(s):  
F. Coceani ◽  
N. C. Hamilton ◽  
J. Labuc ◽  
P. M. Olley
Keyword(s):  
Cytochrome P450 ◽  
Guinea Pig ◽  
Partial Pressure ◽  
Contractile Response ◽  
Muscle Tone ◽  
Ductus Arteriosus ◽  
Inhibitory Effect ◽  
Gas Mixture ◽  
O2 Partial Pressure ◽  
Cytochrome P 450

CO and metyrapone were tested on isolated ductus arteriosus preparations from mature fetal lambs equilibrated at low (4-12 Torr) and high (511-712 Torr) O2 partial pressure (PO2). CO completely reversed the contractile tension of the ductus at either PO2 value and was equally effective in the absence and presence of indomethacin. CO relaxation still occurred when the tissue was exposed to a gas mixture having a CO-to-O2 ratio of 0.27. The inhibitory effect of CO on the O2-contracted ductus was variably reversed by light. Metyrapone was also a relaxant agent, and its action was greater at low than at high PO2. Unlike the lamb ductus, the O2-constricted guinea pig ductus did not respond to CO (maximum CO-to-O2 ratio around 1), whereas it was relaxed by metyrapone. These findings implicate a cytochrome P450-catalyzed enzymic process in the maintenance of muscle tone of the lamb ductus arteriosus and in the contractile response of the vessel to O2.

Morphologic Evidence of Accelerated Closure of the Ductus Arteriosus in Preterm Infants

PEDIATRICS ◽  
1980 ◽  
Vol 65 (5) ◽  
pp. 872-880
Author(s):  
Donald T. King ◽  
George C. Emmanouilides ◽  
James C. Andrews ◽  
Frank M. Hirose
Keyword(s):  
Preterm Infants ◽  
Gestational Age ◽  
Ductus Arteriosus ◽  
Chronic Hypertension ◽  
Moderate Degree ◽  
Autopsy Study ◽  
Histologic Evidence ◽  
Abruptio Placenta ◽  
Postnatal Closure ◽  
Age Of Death

In preterm infants, closure of the ductus arteriosus (DA) is often delayed, especially in those with respiratory distress syndrome (RDS). However, it has been suggested that functional closure of the DA may occur as early as 24 hours of age in some preterm infants exposed to intrauterine stress, and this is usually associated with decreased incidence of RDS. This suggests that accelerated maturation of the DA as well as of the lungs occurs in utero. Accordingly, histologic evidence of accelerated maturation of the DA was sought in a prospective autopsy study of 55 preterm infants ranging in gestational age from 19 to 32 weeks. There were four infants with clinically closed DA which showed histologic evidence of closure. The birth weight of these four infants ranged from 750-1,100 gm, the gestational age ranged from 24-32 weeks, and age of death was 39 hours to 6 days. The immediate causes of death were intracerebral hemorrhage or intrapulmonary hemorrhage, or both. Obstetric complications included chronic second trimester vaginal bleeding, abruptio placenta, malnutrition, diabetes, pulmonic stenosis of moderate degree, and chronic hypertension. These findings support the hypothesis that in some preterm infants exposed to chronic intrauterine stress, maturation of the DA is accelerated. This may result clinically in effective postnatal closure of the DA.

Effect of chronic hypoxia on myometrial responsiveness in the pregnant rat

1996 ◽  
Vol 270 (3) ◽  
pp. E477-E482 ◽  
Author(s):  
J. W. Rhee ◽  
L. D. Longo ◽  
W. J. Pearce ◽  
N. H. Bae ◽  
G. J. Valenzuela ◽  
...  
Keyword(s):  
Binding Sites ◽  
Chronic Hypoxia ◽  
Contractile Response ◽  
Plasma Concentrations ◽  
Hypoxic Exposure ◽  
Normal System ◽  
Pregnant Rat ◽  
Near Term ◽  
Air Control

Mechanisms involving the timing of normal parturition are not well understood in most animal species. To gain a greater understanding of the mechanisms, we employed hypoxia to perturb the normal system of parturition. The present study was designed to investigate the effects of chronic hypoxia on myometrial contractility in the near-term pregnant rat. Rats were exposed to room air (control) or to continuous hypoxia (10.5% O2) either from experimental days 19 through 21 (2-day exposure) or from experimental days 15 through 21 (6-day exposure). On day 21, blood was collected for hormone assays, and the uterine horns were collected from each dam. One horn was snap-frozen in liquid nitrogen for oxytocin (OT) receptor analysis, and the other was used for in vitro assessment of myometrial contractile responses to cumulative doses of OT or arginine vasopressin (AVP). Hypoxic exposure resulted in approximately 60% reduction of the maximal myometrial contractile response to OT and a significant reduction in OT binding sites from 256.9 +/- 34.9 to 84.9 +/- 21.3 fmol/mg protein (P<0.01). In contrast, the contractile response to AVP was unaffected after exposure to chronic hypoxia (P> 0.05). Additionally, we observed no difference in the plasma concentrations of estrogen, progesterone, and corticosterone. We conclude that chronic hypoxia decreased the effectiveness of OT-specific contractile mechanisms, at least partially through a decrease in OT binding sites.

5-Hydroxytryptamine potentiates vasoconstrictor effect of endothelin-1

1992 ◽  
Vol 262 (4) ◽  
pp. H931-H936
Author(s):  
B. C. Yang ◽  
W. W. Nichols ◽  
D. L. Lawson ◽  
J. L. Mehta
Keyword(s):  
Receptor Antagonist ◽  
Channel Blocker ◽  
Contractile Response ◽  
Thromboxane A2 ◽  
Threshold Concentration ◽  
Endothelin 1 ◽  
Voltage Dependent ◽  
Voltage Dependent Calcium Channels ◽  
Ly 53857 ◽  
A2 Receptors

Interactions between 5-hydroxytryptamine (5-HT) and endothelin-1 (ET-1) relative to contraction of rat aortic rings were examined in this study. Pretreatment of rings with threshold concentration of 5-HT potentiated the subsequent contractile response to ET-1. However, pretreatment with threshold concentration of ET-1 did not potentiate the contractile response to 5-HT. The 5-HT receptor antagonist LY 53857 blocked the synergistic contractile effects of 5-HT and ET-1 on rat aortic rings. Indomethacin and the thromboxane A2/endoperoxide receptor antagonist SQ 29548 also attenuated (P less than 0.05) the synergistic contractile effects of 5-HT and ET-1, suggesting release of thromboxane A2 or expression of thromboxane A2 receptors during this interaction. The calcium channel blocker verapamil also decreased the synergistic contractile effects of 5-HT and ET-1. Contraction of aortic rings by 5-HT alone was abolished by LY 53857 and attenuated by verapamil, diltiazem, and SQ 29548. Decrease in the force of contraction by verapamil as well as diltiazem indicates activation of voltage-dependent calcium channels during 5-HT-mediated contraction and perhaps during amplification of the vasoconstrictor activity of ET-1 by 5-HT.

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