Selective glycolysis blockade in guinea pig pulmonary artery and aorta reverses contractile and electrical responses to acute hypoxia.
The goal of this study was to clarify the mechanisms of hypoxic pulmonary vasoconstriction (HPV) reversal following selective glycolysis blockade and to assess possible contribution of endothelial electrogenesis to this phenomenon as a trigger mechanism. We compared smooth muscle (SM) contractility and endothelial cell (EC) membrane potential (MP) during acute hypoxia before and after glycolysis blockade. MPs were recorded from the endothelium of guinea pig pulmonary artery (GPPA) and thoracic aorta (GPTA) using the patch-clamp technique. Acute hypoxia caused hyperpolarization in GPTA EC, while EC from GPPA were depolarized. Also, acute hypoxia elicited constriction in isolated GPPA and dilatation in GPTA. Selective glycolysis inhibition always reversed both electrical and contractile responses in GPPA to hypoxia, but in GPTA this only occurred in 30% of experiments. It is likely that an unknown glycolysis-driven mechanism in EC mediates vascular tone regulation under hypoxia and underlies the paradoxical difference in the response of pulmonary and systemic arterial SM to hypoxia. Our data suggest that HPV development in GPPA might, at least partially, be driven by EC depolarization spreading to the underlying SM cells.
Department of Experimental Therapeutics, Institute of Pharmacology and Toxicology, 14 E. Pottier Str., 03068, Kiev, Ukraine. tonysolpharm@ukrpost.ua
Anatoly I
AI
Soloviev
Alexander I
AI
Bondarenko
Igor V
IV
Kizub
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D015687:Cell Hypoxia; D042783:Endothelial Cells / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000502:physiology; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology*