Detergent and methylene blue affect endothelium-dependent vasorelaxation and pressure/flow relations in rat blood...

1. The autoperfused superior mesenteric arterial bed of the rat was used to study the opposition by carbachol of pressor responses to noradrenaline and the effects of methylene blue, the detergent CHAPS and indomethacin on pressure/flow relations. 2. Carbachol (1 ng-3 micrograms) reduced the pressor response to 1 microgram noradrenaline in a dose-dependent manner with an ED50 = 25.5 +/- 6.0 ng and a maximum inhibition of 51.8 +/- 1.9%. Perfusion of the mesenteric bed with 0.3% CHAPS in saline for 150s abolished the reduction by carbachol of the noradrenaline pressor response. The effect of carbachol was also abolished by infusion of 1% methylene blue into the mesenteric vascular bed. Indomethacin (5 mg kg-1) was without significant effect on the carbachol opposition of noradrenaline pressor responses. None of the 3 treatments had any effect on the response to 1 microgram noradrenaline. 3. Perfusion with CHAPS before determination of pressure/flow relations, or infusion of methylene blue during their determination, steepened the regression of pressure upon flow to the same extent; at all the flow rates used (0.4-3.54 ml min-1) pressure was greater as a result of the treatment than in control animals. Pretreatment with indomethacin had no effect on pressure/flow relations. 4. It is concluded that carbachol opposition to noradrenaline pressor responses in the blood perfused superior mesenteric arterial bed of the rat shows the characteristics of being mediated by endothelium-dependent relaxing factor (EDRF). Since vascular resistance increases more rapidly than in controls when the endothelium is functionally inhibited by treatment with CHAPS or perfusion with methylene blue, it appears that EDRF has a role in vivo in the modulation of myogenic vascular tone.