Does the cofilin pathway play a role in closure of the avian ductus arteriosus (Gallus gallus)?

Abstract

The ductus arteriosus (DA) is an oxygen-sensitive embryonic blood vessel present in all developing amniotes. The DA connects the pulmonary artery to the aorta to shunt blood away from nonfunctioning lungs and toward the fetal respiratory organ. Increased arterial PO2 after birth or hatch initiates permanent closure of the DA. Permanent closure of this vessel upon birth or hatch establishes proper separation of the pulmonary and systemic circuits in the mammalian and avian neonate. Smooth muscle contraction is governed by myosin light chain kinase (MLCK), which stimulates increased cross-bridge cycling, and through increases in actin polymerization. Actin polymerization occurs in smooth muscle cells when globular actin (G actin) polymerizes to form filamentous actin (F actin), allowing for greater contractile strength. Regulation of actin polymerization in some blood vessels involves the cofilin pathway. P-21 activated kinase (PAK) regulates Lim kinase, which inhibits the actin depolymerizer cofilin. Activation of cofilin results in the severing of filamentous actin, leading to decreased tension of vessels. In this study we examined the role of the cofilin pathway in maintaining DA patency in the embryonic stage and subsequent constriction and closure during hatching in the chicken. Following Isoflurane inhalation, embryonic DA were excised from developing chickens and vessel tension was evaluated using wire myography. The DA were maintained in physiological saline solution and low oxygen conditions before being exposed to inhibitors of the PAK pathway followed by exposure to elevated oxygen. To examine the role of the cofilin pathway in DA physiology, we used IPA3 to inhibit P-21 activated kinase, and LIMKi3 and SR7826 to inhibit Lim kinase. Exposure to IPA3 did not alter baseline vessel tension or contraction in response to elevated oxygen. Inhibition of Lim kinase did not disrupt vessel tension or responsiveness to elevated oxygen levels. Our findings suggest that the cofilin pathway is not involved in regulating tension dynamics during the embryonic development and subsequent closure of the DA at hatching. This research was funded by Grant R15HL14887 from NIH-NHLBI. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.