Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKC β/Mitochondrial Oxidant Signaling.

Intermittent Hypoxia Augments Pulmonary Vasoconstrictor Reactivity through PKCβ/Mitochondrial Oxidant Signaling. Am J Respir Cell Mol Biol. 2020 Feb 12;: Authors: Snow JB, Norton CE, Sands MA, Weise-Cross L, Yan S, Herbert LM, Sheak JR, Gonzalez Bosc LV, Walker BR, Kanagy NL, Jernigan NL, Resta TC Abstract Pulmonary vasoconstriction resulting from intermittent hypoxia (IH) contributes to pulmonary hypertension (pHTN) in patients with sleep apnea (SA), although the mechanisms involved remain poorly understood. Based on prior studies in SA patients and animal models of SA, the objective of this study was to evaluate the role of PKCβ and mitochondrial reactive oxygen species (mitoROS) in mediating enhanced pulmonary vasoconstrictor reactivity following IH. We hypothesized that PKCβ mediates vasoconstriction through interaction with the scaffolding protein PICK1, activation of mitochondrial ATP-sensitive potassium channels (mitoKATP), and stimulated production of mitoROS. We further hypothesized that this signaling axis mediates enhanced vasoconstriction and pHTN following IH. Rats were exposed to IH or sham conditions (7 h/day; 4 wks). Chronic oral administration of the antioxidant TEMPOL or the PKCβ inhibitor LY-333,531 abolished IH-induced increases in right ventricular (RV) systolic pressure and RV hypertrophy. Furthermore, scavengers of O2- or mitoROS prevented enhanced PKCβ-dependent vasoconstrictor reactivity to endothelin-1 ...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research