Regional differences in nitric oxide‐mediated vasorelaxation in porcine pulmonary arteries

Abstract

Several previous investigations have shown improved oxygenation when ventilator-treated patients with acute lung injury are turned prone. In a previous human study, we demonstrated higher Ca(2+)-dependent nitric oxide synthase (NOS) activity in dorsal than in ventral parts of the lung. The current investigation was designed to determine whether Ca(2+)-dependent NOS activity was different in dorsal and ventral porcine lung regions. In addition, possible differences in vascular responses to nitroprusside or secondary to acetylcholine- or bradykinin-stimulated NO production were studied in dorsal and ventral pulmonary arteries. In the study, 20 pigs were used. Lung biopsies and pulmonary arterial rings were harvested from ventral and dorsal lung regions. NOS activity was determined by citrulline assay in the presence and absence of the calcium chelator ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid (EDTA) to discriminate between Ca(2+)-dependent and Ca(2+)-independent NOS activity. In organ baths, in submaximally contracted arterial rings, vasorelaxation induced by acetylcholine, bradykinin and nitroprusside was measured. Ca(2+)-dependent NOS activity was higher in dorsal parts (87.2 +/- 9.1 citrulline units) than in ventral parts (62.2 +/- 10.1 citrulline units, P < 0.05) of porcine lung. There was a greater relaxation in dorsal than in ventral pulmonary arterial rings induced by both acetylcholine and bradykinin. Nitroprusside relaxed both sites equally. Our results show that endothelial-derived NO is an important factor influencing the differences between dorsal and ventral lung regions in vasorelaxing activity in porcine pulmonary arteries. This finding provides an explanation for the improved oxygenation when patients with severe acute lung insufficiency are turned prone.