Clinical aspects of hypoxic pulmonary vasoconstriction

Abstract

SUMMARYAlthough frequently unrecognized, hypoxic pulmonary vascular disease is an important cofactor in the morbidity and mortality of a wide spectrum of disease processes. The hypoxic response incorporates two distinct phases, the acute hypoxic vasoconstrictor response and vascular remodelling associated with prolonged alveolar hypoxia. Understanding of the mechanisms causing both processes has increased rapidly and may result in the near future in specific treatment aimed at correcting underlying physiological abnormalities. However, currently available therapies remain limited to correction of the hypoxaemia and generalized non-specific pulmonary vasodilatation. The recent development of inhaled NO therapy represents a significant advance in the management of the acute hypoxic pulmonary vasoconstriction occurring during critical illness.

Sodium Tanshinone IIA Sulfonate Inhibits Canonical Transient Receptor Potential Expression in Pulmonary Arterial Smooth Muscle from Pulmonary Hypertensive Rats

“…Recent studies indicated that STS exerts protective effects on hypoxic pulmonary hypertension, including lowering pulmonary artery pressure and decreasing pulmonary artery thickness and right ventricular hypertrophy (19). These effects were suggested to be achieved partially through the regulation of intracellular Ca 21 homeostasis in pulmonary arterial smooth cells (PASMCs) (19,20); however, the underlying detailed mechanisms remain largely unclear and deserve further investigation. The elucidation of the involved mechanisms will serve as a rationale for the potential clinical application of STS or tanshinone IIA in PAH treatment, which could benefit thousands of patients with PAH by greatly reducing their medical expenses.…”

“…Among numerous mechanisms that have been identified as influencing the development of PAH, hypoxia is thought to be a pivotal factor triggering pulmonary vascular contraction (21) and remodeling (22). Animals such as rat and mouse exposed to chronic hypoxia developed chronically hypoxia pulmonary hypertension (CHPH) in less than 3 weeks (23)(24)(25) (27,(29)(30)(31).…”

“…Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA isolated as the major active component from Danshen, was recently reported to be effective in attenuating the characteristic pulmonary vascular changes associated with chronically hypoxic pulmonary hypertension (CHPH); however, the underlying detailed mechanisms are poorly understood. In this study, we investigated the effects of STS on basal intracellular Ca 21 concentration ([Ca 21 ] i ) and store-operated Ca 21 entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn 21 quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O 2 , 21 d) was increased by 59%, and basal [Ca 21 ] i was increased by 119%; this effect was inhibited by intraperitoneal injection of STS.…”

“…In this study, we investigated the effects of STS on basal intracellular Ca 21 concentration ([Ca 21 ] i ) and store-operated Ca 21 entry (SOCE) in distal pulmonary arterial smooth muscle cells (PASMCs) exposed to prolonged hypoxia or isolated from CHPH rats. SOCE measured by Mn 21 quenching of Fura-2 fluorescence in PASMCs from rats exposed to chronic hypoxia (10% O 2 , 21 d) was increased by 59%, and basal [Ca 21 ] i was increased by 119%; this effect was inhibited by intraperitoneal injection of STS. These inhibitory effects of STS on hypoxic increases of SOCE and basal [Ca 21 ] i were associated with reduced expression of canonical transient receptor potential (TRPC)1 and TRPC6 in distal pulmonary arterial smooth muscle and decreases on right ventricular pressure, right ventricular hypertrophy, and peripheral pulmonary vessel thickening.…”

Μελέτη του μηχανισμού ενεργοποίησης του παράγοντα που επάγεται από την υποξία HIF-1a in vitro και σε πρωτογενείς καλλιέργειες λείων μυϊκών κυττάρων αεραγωγών

“…Η χρόνια υποξία η οποία προκαλείται σε διάφορες παθολογικές καταστάσεις όπως άσθµα και κυστική ίνωση ή εµφανίζεται σε κατοίκους περιοχών µε υψηλό υψόµετρο έχει ως αποτέλεσµα την ανακατασκευή της πνευµονικής αρτηρίας και χρόνια υπέρταση [122,123]. Επιπλέον µελέτες σε ποντίκια τα οποία εκτέθηκαν για 3 βδοµάδες σε υποξία (10% Ο 2 ) έδειξαν την πάχυνση του εσωτερικού τοιχώµατος των µικρών αρτηριών της πνευµονικής κυκλοφορίας και πνευµονική υπέρταση.…”