Increased Constriction of the Ductus Arteriosus with Combined Administration of Indomethacin and &lt;i&gt;L&lt;/i&gt;-NAME in Fetal Rats

Takizawa, Takeo; Kihara, Takumi; Kamata, Akira

doi:10.1159/000047122

Cited by 13 publications

(18 citation statements)

References 20 publications

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“…Any interference with PGE 2 is, in fact, amenable to compensation by alternative relaxing mechanisms (3,20,21). Furthermore, PGE 2 itself plays a role not only in prenatal patency of the vessel but also in its closure postnatally (16,18,28,29).…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P-450 3A13 and endothelin jointly mediate ductus arteriosus constriction to oxygen in mice

Baragatti

Ciofini

Scebba

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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The fetal ductus arteriosus (DA) contracts to oxygen, and this feature, maturing through gestation, is considered important for its closure at birth. We have previously obtained evidence of the involvement of cytochrome P-450, possibly of the 3A subfamily (CYP3A), in oxygen sensing and have also identified endothelin (ET)-1 as the attendant effector for the contraction. Here, we examined comparatively wild-type (WT) and CYP3A-null (Cyp3a(-/-)) mice for direct validation of this concept. We found that the CYP3A subfamily is represented only by CYP3A13 in the WT DA. CYP3A13 was also detected in the DA by immunofluorescence microscopy, being primarily colocalized with the endoplasmic reticulum in both endothelial and muscle cells. However, a distinct signal was also evident in the plasma membrane. Isolated DAs from term WT animals developed a sustained contraction to oxygen with transient contractions superimposed. Conversely, no tonic response occurred in Cyp3a(-/-) DAs, whereas the phasic response persisted unabated. Oxygen did not contract the preterm WT DA but caused a full-fledged contraction after retinoic acid (RA) treatment. RA also promoted an oxygen contraction in the Cyp3a(-/-) DA. However, responses of RA-treated WT and Cyp3a(-/-) mice differed in that only the former abated with ET-1 suppression. This implies the existence of an alternative target for RA responsible for the oxygen-induced contraction in the absence of CYP3A13. In vivo, the DA was constricted in WT and Cyp3a(-/-) newborns, although with a tendency to be less narrowed in the mutant. We conclude that oxygen acts primarily through the complex CYP3A13 (sensor)/ET-1 (effector) and, in an accessory way, directly onto ET-1. However, even in the absence of CYP3A13, the DA may close postnatally thanks to the contribution of ET-1 and the likely involvement of compensating mechanism(s) identifiable with an alternative oxygen-sensing system and/or the withdrawal of relaxing influence(s) operating prenatally.

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Section: Discussionmentioning

confidence: 99%

Cytochrome P-450 3A13 and endothelin jointly mediate ductus arteriosus constriction to oxygen in mice

Baragatti

Ciofini

Scebba

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…In this study, we used a similar dose of L-NAME, as used in previous reports. L-NAME, at the concentration used (50 mg/kg), blocks ultrasound-induced upregulation of NOS (7,8,(15)(16)(17)(18)(19)(20). Therefore, ultrasound-enhanced myocardial tissue perfusion in the setting of coronary occlusion is likely to be due to NO-mediated enhancement of coronary artery collateral flow.…”

Section: Discussionmentioning

confidence: 99%

Ultrasound energy improves myocardial perfusion in the presence of coronary occlusion

Siegel

Suchkova²,

Miyamoto

et al. 2004

Journal of the American College of Cardiology

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“…Among them, prostaglandin (PG) E 2 plays a prime role, and its action is likely supplemented by nitric oxide (NO) and carbon monoxide (CO). NO activity, in particular, changes through development in a reciprocal manner with PGE 2 (18,21,26) and may also increase following any loss of PGE 2 function (1,23). Hydrogen sulfide (H 2 S), in contrast, has seemingly no role in the ductus, at least with the chicken embryo (28), despite substantial work in mammals documenting a vasoregulatory function for the compound in both adult (17,29) and neonate (16).…”

mentioning

confidence: 99%

Hydrogen sulfide in the mouse ductus arteriosus: a naturally occurring relaxant with potential EDHF function

Baragatti

Ciofini

Sodini

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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We have previously reported that bradykinin relaxes the fetal ductus arteriosus via endothelium-derived hyperpolarizing factor (EDHF) when other naturally occurring relaxants (prostaglandin E2, nitric oxide, and carbon monoxide) are suppressed, but the identity of the agent could not be ascertained. Here, we have examined in the mouse whether hydrogen sulfide (H2S) is a relaxant of the ductus and, if so, whether it may also function as an EDHF. We found in the vessel transcripts for the H2S synthetic enzymes, cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS), and the presence of these enzymes was confirmed by immunofluorescence microscopy. CSE and CBS were distributed across the vessel wall with the former prevailing in the intimal layer. Both enzymes occurred within the endoplasmic reticulum of endothelial and muscle cells, whereas only CSE was located also in the plasma membrane. The isolated ductus contracted to inhibitors of CSE (d,l-propargylglycine, PPG) and CBS (amino-oxyacetic acid), and PPG contraction was attenuated by removal of the endothelium. EDHF-mediated bradykinin relaxation was curtailed by both PPG and amino-oxyacetic acid, whereas the relaxation to sodium nitroprusside was not affected by either treatment. The H2S donor sodium hydrogen sulfide (NaHS) was also a potent, concentration-dependent relaxant. We conclude that the ductus is endowed with a H2S system exerting a tonic relaxation. In addition, H2S, possibly via an overriding CSE source, qualifies as an EDHF. These findings introduce a novel vasoregulatory mechanism into the ductus, with implications for antenatal patency of the vessel and its transitional adjustments at birth.

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Increased Constriction of the Ductus Arteriosus with Combined Administration of Indomethacin and <i>L</i>-NAME in Fetal Rats

Cited by 13 publications

References 20 publications

Cytochrome P-450 3A13 and endothelin jointly mediate ductus arteriosus constriction to oxygen in mice

Cytochrome P-450 3A13 and endothelin jointly mediate ductus arteriosus constriction to oxygen in mice

Ultrasound energy improves myocardial perfusion in the presence of coronary occlusion

Hydrogen sulfide in the mouse ductus arteriosus: a naturally occurring relaxant with potential EDHF function

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