Aims: 

It is known that hypoxia causes pulmonary artery constriction normally maintaining optimal ventilation-perfusion matching in the lung but leading to pulmonary hypertension. Although it is known that sustained hypoxic pulmonary vasoconstriction (HPV) is dependent on the endothelium, the signaling pathways remain unclear. The aim of this study was to determine the role of myoendothelial gap junctions in HPV.

Methods: 

The vascular tone was measured on isolated Wistar rat small intrapulmonary arteries (IPA) using a wire myography technique. In vivo experiments were performed on anesthetized with chloralose/urethane Wistar rats with retrograde catheterization of the right ventricle and the left common carotid artery for systolic right ventricular pressure (RVP) and mean arterial pressure (MAP) registration.

Results: 

Hypoxia (PO2 -2–3 mmHg) elicited a biphasic constriction of isolated IPA preconstricted with prostaglandin F 2a (3 mM) or 25 mM K⁺ consisted of the transient phase and the sustained phase following 40 min of hypoxia. Gap junctions' inhibition with 18-glycyrrhetinic acid (18-GA, 30 mM) or heptanol (3.5 mM) had not effect on HPV transient phase but abolished the sustained HPV. Elevation in 18-GA concentration to 60 and 100 mM evoked a suppressing of both HPV phases. In in vivo experiments hypoxia resulted in a biphasic increase in RVP consisted with transient and sustained (during the course of hypoxia 30 min.) phases. In animals treated orally with 18-GA (25 mg/kg) 20 hours before the experiment slight inhibition of the transient phase and complete abolishing of the sustained RVP increase have been observed.

Conclusion: 

Our data indicates that gap junctions involved to the sustained phase of HPV reflecting a novel pathway for signaling during hypoxic pulmonary hypertension development.