Serotonin mediated Ca2+ events are reduced in pulmonary arterial myocytes of chronic hypoxic fetal sheep

Abstract

Serotonin (5HT) is important to pulmonary arterial (PA) reactivity and alterations in 5HT signaling are implicated in pulmonary hypertension in newborns as well as adults. Several reports also provide evidence for alterations in 5HT mediated contractility with maturation and in response to chronic hypoxia (CH). Further to this 5HT 2A receptor activation and Ca 2+ signaling is important to the contractility responses induced by 5HT, and we have evidence that Ca 2+ ‐dependent contractility is reduced with CH in PA from sheep fetus. To delineate the cellular mechanisms associated with the loss in Ca 2+ ‐dependent contractility we tested the hypothesis that 5HT generated Ca 2+ ‐signaling is reduced with CH in fetal sheep. This was examined using in‐situ confocal imaging of Flou‐4 in PA isolated from CH fetus and adult. PA myocytes of CH fetal and adult had spontaneous cytosolic Ca 2+ elevations and 10 μM 5HT induced cytosolic Ca 2+ elevations in myocytes of fetal and adult sheep. The frequency of 5‐HT‐mediated Ca 2+ oscillations in responsive cells was 0.01 ± 0.002 Hz in fetus and 0.021 ± 0.002 Hz in adult while the density of cells exhibiting Ca 2+ elevations was 0.003 ± 0.001 cells/mm 2 /sec in fetus and 10‐fold greater in adult, being 0.03 ± 0.003 cells/mm 2 /sec. The reduced 5HT mediated Ca 2+ signaling in fetal cells may underlie the loss of Ca 2+ ‐dependent contractility previously observed. (Support from NSF, NIH and UM)