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 i...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research

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Journal of Clinical Sleep Medicine, Ahead of Print.
Source: Journal of Clinical Sleep Medicine : JCSM - Category: Sleep Medicine Authors: Source Type: research
AbstractObstructive sleep apnea (OSA) syndrome is the most common sleep-breathing disorder, which is associated with increase cardiovascular morbidity and mortality. OSA increases risk of resistant arterial hypertension, coronary artery disease, heart failure, pulmonary hypertension, and stroke. Studies showed the significant relationship between OSA and cardiac remodeling. The majority of investigations were focused on the left ventricle and its hypertrophy and function. Fewer studies investigated right ventricular structure and function revealing deteriorated diastolic and systolic function. Data regarding left and right...
Source: Heart Failure Reviews - Category: Cardiology Source Type: research
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Source: Open Respiratory Medicine Journal - Category: Respiratory Medicine Tags: Open Respir Med J Source Type: research
High prevalence of obstructive sleep apnea (OSA) in the pulmonary hypertension (PH) population suggests that chronic intermittent hypoxia (CIH) is an important pathogenic factor of PH. However, the exact mecha...
Source: Respiratory Research - Category: Respiratory Medicine Authors: Tags: Research Source Type: research
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Source: Heart and Lung: The Journal of Acute and Critical Care - Category: Respiratory Medicine Source Type: research
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Source: American Journal of Respiratory and Critical Care Medicine - Category: Respiratory Medicine Authors: Tags: Am J Respir Crit Care Med Source Type: research
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