Involvement of Gap Junctions Between Smooth Muscle Cells in The Sustained Hypoxic Pulmonary Vasoconstriction Development

Abstract

It is well known that inhaled hypoxia causes pulmonary artery constriction to maintain optimal ventilation‐perfusion matching in the lung. However, sustained hypoxic pulmonary vasoconstriction (HPV) leads to the development of pulmonary hypertension. The mechanisms of the sustained HPV remain unclear. The aim of this study was to determine the role of gap junctions (GJs) between smooth muscle cells (SMCs) in the sustained HPV development. The vascular tone was measured in isolated rings of bovine intrapulmonary arteries (BIPA) using isometric force measurement technique. Chronic hypoxia (PO2 = 10‐20 Torr) after 13 h elicited the sustained HPV in 3rd‐ and 2nd‐order BIPA precontracted with 30 mM KCl. The endothelium removal had no effect on the sustained HPV amplitude neither in 3rd‐ nor in 2nd‐order BIPA. Inhibition of GJs with 18β‐glycyrrhetinic acid (30 µM) and heptanol (3.5 mM) significantly decreased the sustained HPV amplitude both in deendothelised 3rd‐order and 2nd‐order BIPA. Similarly, a highly selective inhibitor Gap‐27 (100 µM) significantly reduced the sustained HPV amplitude in deendothelised 3rd‐order BIPA. Taken together, these data indicates that GJs between SMCs are involved to the sustained HPV development in bovine pulmonary artery, reflecting possibility of a novel pathway existing for signaling in SMCs during hypoxia that supports HPV. This study was supported by The Fulbright Program and the U.S. Department of State's Bureau of Education and Cultural Affairs to Kizub I.V., 2014