Aims: 

Since endothelial dysfunction induced by increased blood plasma levels of homocysteine is not well understood, we started an investigation of homocysteine effects upon isolated resistance arteries.

Methods: 

We used the wire myograph technique and small mesenteric arteries from male adult Wistar rats. Submaximal reference contractions were induced by 0.01 mM phenylephrine; results expressed as % active tension of the reference value (mean±SEM; n = 6).

Results: 

Homocysteine 0.05mM induces a slow and minor contraction of resting vessels (<10%), only in the presence of endothelium. This effect is completely blocked in arteries where tone is increased by inhibition of basal nitric oxide (NO) release (0.01 mM L-NAME), which confirms the ability of homocysteine to inhibit nitric oxide synthase. However, incubation for 2 hours with 0.05 mM homocysteine does not alter the contraction induced by phenylephrine (in presence/absence of endothelium) or endothelium-dependent relaxation (EDR) induced by 0.01mM carbachol. The EDHF response (EDR in presence of 0.01mM L-NAME and 0.01mM indomethacin) is augmented by 0.05mM homocysteine (p < 0.01). This may reflect a physiological compensation of NO decrease by EDHF, or a novel ability of homocysteine to potentiate the EDHF component. This is difficult to reconcile with the inhibition by homocysteine of calcium-dependent potassium channels (BKCa, involved in EDHF effect) in smooth muscle from rat mesenteric arteries.

Conclusion: 

Global EDR in resistance arteries is not impaired by short-time excessive homocysteine, since reduction in NO release is accompanied by enhancement of the EDHF component.

*CNCSIS grant A/1222, **CNCSIS grant interdisciplinary platform /68.