Acute effects of homocysteine upon endothelium-dependent relaxation of resistance arteries

Increased blood homocysteine (HCY) induces an endothelial dysfunction which is little understood. We used the wire myograph to study this aspect in small mesenteric arteries from male adult Wistar rats. In presence of endothelium HCY 0.05 mM induces a slow minor contraction, which is blocked if tone is increased by inhibition of nitric oxide synthase (NOS) with 0.01 mM L-NAME, confirming the ability of HCY to inhibit NOS. Incubation for 2 h with 0.05 mM HCY does not alter contraction induced by 0.01 mM phenylephrine or endothelium-dependent relaxation induced by 0.01 mM carbachol. The EDHF component of the latter (in presence of 0.01 mM L-NAME and 0.01 mM indomethacin) is augmented by HCY (p < 0.01), reflecting a HCY-induced increase in EDHF release/effect or a compensation via EDHF which occurs when NOS is inhibited by HCY.