Role of glucose in pulmonary artery vasoconstriction during hypoxia

Abstract

We have previously shown that the sustained phase of hypoxic pulmonary vasoconstriction (HPV) is critically dependent on extracellular glucose, though this does not seem to be related to the energy requirements of constriction per se (Leach et al, 2001, J Physiol 536, 211-224). As sustained HPV involves Ca2+ sensitisation, and changes in glucose preferentially affected force development rather than intracellular [Ca2+], we hypothesised that glucose was supporting Rho kinase dependent Ca2+ sensitisation. We examined the effects of varying glucose in small intrapulmonary arteries of the rat on MYPT-1 phosphorylation during HPV, and on the response to PGF2α (which also causes Ca2+ sensitisation) during hypoxia. After 45 min of hypoxia, MYPT-1 phosphorylation was significantly reduced in both 2.5mM (69 ± 11% of phosphorylation in 5mM, n=8, p<0.01) and 0mM glucose (19 ± 4%, n=8, p<0.01). During hypoxia, the concentration-response relationship for PGF2α was progressively suppressed as glucose was reduced (e.g. at 30μM PGF2α :- 5mM: 38 ± 4% of response to 80mM [K+]; 2.5mM: 28 ± 5%; 0mM: 9 ± 1%; n=6, p<0.05 for both). In the absence of extracellular Ca2+ reducing glucose also suppressed PGF2α :-induced tension (e.g. at 30μM PGF2α :- 5mM: 14 ± 1%; 2.5mM: 12 ± 1%; 0mM: 9 ± 1%; n=8, p<0.05 ANOVA). These data suggest that glycolysis is important for supporting Ca2+ sensitisation. Supported by the Wellcome Trust.