A role for the sodium pump in H2O2-induced vasorelaxation in porcine isolated coronary arteries

Hydrogen peroxide (H2O2) has been proposed to act as a factor for endothelium-derived hyperpolarization (EDH) and EDH may act as a ‘back up’ system to compensate the loss of the NO pathway. Here, the mechanism of action of H2O2 in porcine isolated coronary arteries (PCAs) was investigated. Distal PCAs were mounted in a wire myograph and pre-contracted with U46619 (1nM–50μM), a thromboxane A2-mimetic or KCl (60mM). Concentration–response curves to H2O2(1μM–1mM), bradykinin (0.01nM–1μM), sodium nitroprusside (SNP) (10nM–10μM), verapamil (1nM–10μM), KCl (0–20mM) or Ca2+-reintroduction (1μM–10mM) were constructed in the presence of various inhibitors. Activity of the Na+/K+-pump was measured through rubidium-uptake using atomic absorption spectrophotometry. H2O2 caused concentration-dependent vasorelaxations with a maximum relaxation (Rmax) of 100±16% (mean±SEM), pEC50=4.18±0.20 (n=4) which were significantly inhibited by PEG-catalase at 0.1–1.0mM H2O2 (P