HSP20 phosphorylation and interstitial metabolites in hypoxia-induced dilation of swine coronary arteries

Objective: Hypoxia induces coronary artery dilation, but the responsible mechanism is largely unknown. Many stimuli induce arterial smooth muscle relaxation by reducing ser19‐myosin regulatory light chain (MLC) phosphorylation. Other stimuli can induce smooth muscle relaxation without reductions in ser19‐MLC phosphorylation. This form of relaxation has been termed force suppression and appears to be associated with heat shock protein 20 (HSP20) phosphorylation on ser16. We investigated whether hypoxia‐induced sustained dilation in swine coronary arteries was promoted without ser19‐MLC dephosphorylation and associated with ser16‐HSP20 phosphorylation. Nitroglycerin vasodilation served as control. Methods: In a pressure myograph, the tunica media of intact pre‐contracted (PGF2α; 10−5 m) porcine coronary artery segments were cannulated using a microdialysis catheter. Diameter responses and interstitial lactate/pyruvate ratios were studied during 90 min hypoxia, hypoxia + reoxygenation (60 min), nitroglycerin (100 μm, 90 min), and nitroglycerin + wash‐out (60 min). The arterial segments were snap‐frozen and analysed for ser16‐HSP20 phosphorylation and ser19‐MLC phosphorylation. Results: The normalized diameter responses to hypoxia (6.1 ± 4.3%) and nitroglycerin (12.6 ± 1.6%) were both significantly greater than normoxic control arteries (−10.5 ± 1.8%, anova, P