Functional Closure of the Ductus Arteriosus at Birth: Evidence against an Intermediary Role of Angiotensin II

Abstract

The fetal ductus arteriosus (DA) closes postnatally first functionally and then structurally. Normal rise in blood oxygenation is regarded as a prime trigger, but closure may occur more slowly without this stimulus. Here, our aim wasto assess the role of angiotensin II (Ang II) in functional closure of DA since its action may not be conditioned by oxygen. Experiments were performed with wild-type fetal and neonatal mice, using whole-body freezing technique to assess DA caliber in vivo. Transcripts for Ang II type 1 (AT₁R) and type 2 (AT₂R) receptors were also examined. We found thatthe AT₁R antagonist olmesartan had no effect in the fetus, but delayed ductus closure in the neonate. However, this response was short-lived and disappeared upon concomitant treatment with the AT₂R antagonist PD123319. Coincidentally, olmesartan promoted the Agtr2 transcript. We conclude that AT₁R-based Ang II has no role in the functional closure of DA. Conversely, the compound may modulate this process through AT₂R-mediated vasodilatation.

Molecular and Mechanical Mechanisms Regulating Ductus Arteriosus Closure in Preterm Infants

“…They exert their anti-inflammatory effects through the inhibition of endogenous prostaglandins. Similar effects have been reported with black tea, resveratrol, mate tea, orange juice and dark chocolate ( 207 ). Excessive consumption of such foods by the pregnant woman may influence the dynamics of the DA, by inhibiting COX and PG synthesis pathway.…”

“…Similarly, postnatal corticosteroid administration may constrict the ductus ( 206 ). Angiotensin II does not have a role in ductal closure after birth ( 207 ).…”

Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data

“…ATII-R1 inhibits adenylate cyclase, activates phospholipase C, and causes vasoconstriction in other vascular beds (39). However, its role in ductus closure is still in question (40).…”

Single nucleotide polymorphisms in AGTR1, TFAP2B, and TRAF1 are not associated with the incidence of patent ductus arteriosus in Japanese preterm infants

“…Angiotensin II receptors can be one of two types: type 1 and type 2 . A recent study showed that the angiotensin II type 2 receptor, but not the type 1 receptor, played a role in the functional closure of DA . Thus, genetic polymorphisms in AGTR1 might not influence the incidence of PDA in preterm infants.…”