METHYLENE-BLUE ATTENUATES VASODILATATION AND ENHANCES VASOCONSTRICTION IN RESPONSE TO ENDOTHELIN-1 IN THE PIG NASAL-MUCOSA

In thiopentone anaesthetized pigs (n = 10), simultaneous recordings of the vasomotor response to local intra-arterial infusion of endothelin-1 and -3 were performed in three different vascular compartments of the nasal mucosa. Sphenopalatine artery blood flow (reflecting nasal blood flow), nasal cavity volume (representing blood content in capacitance vessels) and laser Doppler flowmeter signal (reflecting superficial mucosal blood flow) increased in response to low doses (4 x 10(-9) to 4 x 10(-8) moles) of endothelin-1. In contrast, marked vasoconstriction (up to 50% of arterial blood flow reduction) occurred upon higher doses (4 x 10(-7) to 4 x 10(-6) moles). Endothelin-3 (4 x 10(-9) to 4 x 10(-6) moles) evoked at the highest dose a long-lasting increase of systemic arterial blood pressure resulting in a 22 +/- 4% increase in nasal vascular resistance. After local intra-arterial pretreatment with methylene blue (4 x 10(-4) mol), the vasodilatory responses to low doses of endothelin-1 were abolished for the three vascular parameters studied, whereas the vasoconstrictor responses in resistance and capacitance vessels evoked by higher doses of endothelin-1 were increased. In contrast, the laser Doppler flowmeter signal reduction in response to endothelin-1 was markedly attenuated. The vasodilatatory effect of substance P was abolished after methylene blue probably due to interference with effects of endothelium dependent relaxing factor (EDRF). These observations suggest that in the pig nasal mucosa in vivo, exogenous endothelin-1 induces a dose-dependent reduction of blood flow in resistance and capacitance vessels and in superficial mucosa. The vasodilatation observed in response to low doses of endothelin-1 seems to be sensitive to methylene blue and similar to the effect for substance P, suggesting involvement of EDRF production.