ADP-ribosyl Cyclase and Cyclic ADP-ribose Hydrolase Act as a Redox Sensor A PRIMARY ROLE FOR CYCLIC ADP-RIBOSE IN HYPOXIC PULMONARY VASOCONSTRICTION

摘要: Hypoxic pulmonary vasoconstriction is unique to arteries and serves match lung perfusion ventilation. However, in disease states this process can promote hypoxic hypertension. associated with increased NADH levels artery smooth muscle intracellular Ca2+ release from ryanodine-sensitive stores. Because cyclic ADP-ribose (cADPR) regulates ryanodine receptors synthesized β-NAD+, we investigated the regulation by β-NADH of cADPR synthesis metabolism role vasoconstriction. Significantly higher rates occurred homogenates arteries, compared systemic arteries. When β-NAD+:β-NADH ratio was reduced, net amount accumulated increased. This due, at least part, inhibition hydrolase β-NADH. Furthermore, hypoxia induced a 10-fold increase muscle, membrane-permeant antagonist, 8-bromo-cADPR, abolished rings. We propose that cellular redox state may be coupled via an enhanced synthesis, activation receptors, sarcoplasmic reticulum release. redox-sensing pathway offer new therapeutic targets for