EFFECTS OF HOMOCYSTEINE ON ACETYLCHOLINE-INDUCED AND ADENOSINE-INDUCED VASODILATATION OF PANCREATIC VASCULAR BED IN RATS

1 Epidemiological and experimental data have shown that homocysteine m ay provoke vascular lesions and that moderate homocysteinaemia may con stitute an independent risk factor for vascular disease. It is now doc umented that homocysteine damages human endothelial cells in culture, possibly by producing hydrogen peroxide in an oxygen-dependent reactio n. 2 In this study, we have examined the direct effect of this sulphur amino acid on pancreatic vascular resistance. Experiments were perfor med on the vascular bed of the rat isolated pancreas perfused al const ant pressure; thus, any change in pancreatic vascular resistance resul ted in a change in the flow rate. D,L-Homocysteine perfused for one ho ur at three different concentrations (200 mu M, 2 mM, 20 mM) did not i nduce any significant change in the flow rate per se. Homocysteine inf usion for 30 min at a concentration of 200 mu M or 2 mM abolished the endothelium-dependent vasodilatation induced by acetylcholine (0.05 mu M), but did not modify adenosine (1.5 mu M)-induced vasodilatation. 3 The effect of D,L-homocysteine (200 mu M or 2 mM) cannot be ascribed to a direct antimuscarinic effect since 30 min pretreatment of rat ile um with these concentrations did not significantly change the contract ile effect of increasing concentrations of acetylcholine (0.015-15 mu M). 4 Preincubation of human umbilical vein endothelial cells with D,L -homocysteine (0.2-5.0 mM) had no significant effect on overall cell n umber or viability during 18 h of incubation; the endothelial cells ex posed to concentrations up to 5 mM exhibited a spindle-shaped, whirled pattern. This pattern was reversed 48 h after the removal of homocyst eine. A cytotoxic effect was seen after 18 h incubation in 10 mM D,L-h omocysteine. 5 In conclusion, an acute infusion of homocysteine altere d acetylcholine endothelium-induced vasodilatation, whereas the adenos ine vasodilatator effect was insensitive to the deleterious action of homocysteine in vitro.