The influence of
methylene blue, an inhibitor of
soluble guanylate cyclase, on responses to ventilatory and precapillary
hypoxia was investigated in the intact-chest cat under conditions of controlled blood flow and constant left atrial pressure. Because
methylene blue increased vascular tone, responses to
hypoxia were compared when lobar arterial pressure was raised to similar levels with
U 46619 and with
methylene blue. When lobar arterial pressure was raised with
U 46619, ventilation with 7.5% O2 increased lobar arterial pressure significantly. Infusion of
methylene blue in concentrations that raised lobar arterial pressure to a value similar to that attained with
U 46619 prevented the pressor response to
hypoxia, and a significant depressor response was unmasked. The depressor response to
hypoxia in the
methylene blue-treated animal was not altered by
meclofenamate but was blocked by
propranolol. A reduction in lobar arterial perfusate PO2 induces an increase in pulmonary vascular resistance in the cat, and this response was prevented by
methylene blue. During
methylene blue infusion, the
vasodilator response to
acetylcholine was reduced, whereas the response to
isoproterenol was not altered. Although the response to
hypoxia was prevented, the pressor response to
prostaglandin F2 alpha was not changed. The response to ventilatory
hypoxia was enhanced by
propranolol or
ICI 118551, suggesting that the response is modulated by circulating
catecholamines that are probably of adrenal origin. The effects of
methylene blue on vascular tone and responses to
hypoxia and
acetylcholine were reversible, and responses returned to control value after the infusion was terminated.(ABSTRACT TRUNCATED AT 250 WORDS)