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

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 was to 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 that the 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.