Action of methylene blue and haemoglobin in rabbit aorta in relation to the surface of drug entry.

The effect of methylene blue and haemoglobin has been evaluated by using a procedure of restricting drug entry to one surface of rabbit aortic rings. In preparations precontracted with noradrenaline, methylene blue and haemoglobin produced, via the intima, an additional rapid and endothelium-dependent contraction. While haemoglobin was without effect via the adventitia, methylene blue produced a slow endothelium-independent contraction that was diminished but not abolished in reserpine-pretreated animals. This augmentation of the noradrenaline-induced contraction produced by methylene blue via the adventitia in reserpine-pretreated rabbits was observed also with phenylephrine but not with methoxamine. Methylene blue, when added to aortic rings incubated with 3H-(-)-noradrenaline, interfered with the neuronal uptake of this amine and enhanced the outflow of 3H. In conclusion, methylene blue and haemoglobin enhanced noradrenaline-induced contraction by an endothelium-dependent mechanism when applied via the intima. Haemoglobin is devoid of effects via the adventitia but methylene blue has indirect sympathomimetic effects. In experiments using intact rings with no restriction to drug entry it was found that the enhancement by haemoglobin of the tyramine-induced response was markedly less than that observed for noradrenaline for the same level of plateau contraction. This finding indicates that the endothelium-derived relaxing factor is more effective on smooth muscle cell layers in the vicinity of intima than on those close to adventitia.