Homocysteine reduces smooth muscle [Ca2+]i and constrictor responses of isolated arterioles.
Chronic elevation of plasma homocysteine concentration has been shown to be associated with impaired vascular function. The acute direct effect of homocysteine on the tone and vasoactive responses of arterioles and the possible underlying mechanisms, however, have not yet been elucidated. Thus arterioles were isolated from gracilis muscle of rats (d: approximately 130 microm) and their diameter was measured by videomicroscopy. Homocysteine (10(-6)-10(-4) M) elicited dose-dependent dilation of arterioles (maximum: 44+/-6% at 10(-4) M). The dilation was not affected by the presence of the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester or by removal of the endothelium, or the free radical scavenger catalase and superoxide dismutase, or the K+ channel inhibitors glibenclamide, 4-aminopyridine, or tetraethyl ammonium. Incubation of vessels with homocysteine (10(-4) M, 20 min) did not affect dilations to acetylcholine or sodium nitroprusside, whereas it significantly decreased constrictions to norepinephrine (at 10(-6) M; control: 57+/-7%, homocysteine: 21+/-5%) and to the thromboxane A2 analogue U46619 (at 10(-8) M: control: 44+/-3%, homocysteine: 20+/-4%). Homocysteine (10(-4) M), similar to the voltage-operated Ca2+ channel inhibitor nitrendipine (10(-8) M), significantly decreased the arteriolar smooth muscle [Ca2+]i as assessed by changes in the fura-2 ratiometric signal (R(Ca), -6+/-1% and -24+/-3%, respectively). These data suggest that in isolated arterioles homocysteine decreases pressure-induced tone and responses to vasoconstrictor agents, likely by altering Ca2+ signaling of arteriolar smooth muscle.
Ungvari
Z
Z
Institute of Pathophysiology, Semmelweis University of Medicine, Budapest, Hungary.
Koller
A
A
D000818:Animals; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006710:Homocysteine / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D006710:Homocysteine; D002118:Calcium