Role of neutral sphingomyelinase‐derived ceramide in the response to oxygen in the chicken ductus arteriosus

Abstract

Ceramide is a sphingolipid‐derived second messenger modulating different signalling pathways and playing an important role in numerous physiological processes such as cell growth, apoptosis and differentiation. In the present study we have analysed the role of ceramide in the vasoactive effects of oxygen in the chicken ductus arteriosus (DA). Experiments were performed in the pulmonary or aortic sides of the DA isolated from chicken fetuses incubated for 15 or 20 days (total incubation: 21‐d) and in myocytes isolated from these tissues. Exposure to oxygen (21%) induced a contractile response in the pulmonary side of 20‐d DA but not in the other preparations. Similarly, oxygen (21%) increased the ceramide content measured by immunocytochemistry in the pulmonary side of 20‐d DA but not in the other preparations. The contractile response induced by oxygen was partially prevented by inhibitors of neutral sphingomyelinases and PCKzeta but not by the classic PKC inhibitor Go6976. Finally, the addition of exogenous C6‐ceramide contracted the pulmonary side of 20‐d DA but had negligible effects in the pulmonary side of 15‐d DA or in the aortic side of 20‐d DA. In conclusion, neutral sphingomyelinase‐derived ceramide plays a role in the oxygen induced contraction of chicken DA. Supported by "Fundación de Investigación Médica Mutua Madrileña"