Methylene Blue Enhances Hypoxic Contraction in Isolated Rat Pulmonary Arteries

Abstract

The mechanism of hypoxic pulmonary vasoconstriction remains poorly understood. It is still uncertain whether the effect of hypoxia is directly on the pulmonary artery (PA), or whether there is a vasoactive intermediate produced by some other lung or blood cell. 1 Voelkel NF Mechanisms of hypoxic pulmonary vasoconstriction. Am Rev Respir Dis. 1976; 38: 221-231 Google Scholar In 1978, Weir 2 Weir EK Does normoxic pulmonary vasodilitation rather than hypoxic vasoconstriction account for the pulmonary pressor response to hypoxia. Lancet. 1978; 8062: 476-477 Abstract Scopus (34) Google Scholar suggested that suppression of a normoxic dilator, rather than production of a hypoxic constrictor, might be the mechanism. It has recently been shown that vascular endothelium-derived relaxing factor (EDRF) production and cGMP production are dependent on oxygen tension, although the minimum Po2 required for their production is not known. 3 Griffith TM Edwards DH Newby AC Lewis MJ Henderson AH Production of endothelium derived relaxing factor is dependent on oxidative phosphorylation and extracellular calcium. Cardiovasc Res. 1986; 20: 7-12 Crossref PubMed Scopus (100) Google Scholar , 4 Burke TM Wolin MS Hydrogen peroxide elicits pulmonary artery relaxation and guanylate cyclase activation. Am J Physiol. 1987; 252: H721-H732 PubMed Google Scholar Given this background, we hypothesized that hypoxia might directly suppress the production of pulmonary artery EDRF and/or smooth muscle cGMP. Our study was designed to test this hypothesis in an isolated conduit PA model of hypoxic contraction. We tested whether 2 interventions, removal of EDRF by removal of the endothelium and partial inhibition of the site of action of EDRF, guanylate cyclase, by 10−5 M methylene blue (MB, a dose which inhibits approximately 75% of EDRF stimulated relaxation 5 Martin W Villani GM Jothianandan D Furchgott RF Selective blockade of endothelium-dependent relaxation by hemoglobin and by methylene blue in the rabbit aorta. J Pharmacol Exp Ther. 1985; 232: 708-716 PubMed Google Scholar ), would potentiate subsequent hypoxic contraction.