title: Folic acid improves acetylcholine-induced vasoconstriction of coronary vessels isolated from hyperhomocysteinemic mice: an implication to coronary vasospasm.
abstract: Human atherosclerotic coronary vessels elicited vasoconstriction to acetylcholine (Ach) and revealed a phenomenon of vasospasm. Homocysteine (Hcy) levels are elevated in the atherosclerotic plaque tissue, suggesting its pathological role in endothelial damage in atherosclerotic diseases. Accordingly, we examined the role hyperhomocysteinemia in coronary endothelial dysfunction, vessel wall thickness, lumen narrowing, leading to acute/chronic coronary vasospasm. The therapeutic potential and mechanisms of folic acid (FA) using hyperhomocysteinemic cystathionine beta synthase heterozygote (CBS-/+) and wild type (CBS+/+) mice were addressed. The CBS-/+ and CBS+/+ mice were treated with or without a Hcy lowering agent FA in drinking water (0.03 g/L) for 4 weeks. The isolated mouse septum coronary artery was cannulated and pressurized at 60 mmHg. The wall thickness and lumen diameters were measured by Ion-Optic. The vessels were treated with Ach (10(-8) -10(-5)  M) and, for comparison, with non-endothelial vasodilator sodium nitroprusside (10(-5)  M). The endothelium-impaired arteries from CBC-/+ mice constricted in response to Ach and this vasoconstriction was mitigated with FA supplementation. The level of endothelial nitric oxide synthase (eNOS) was lower in coronary artery in CBS-/+ than of CBS+/+ mice. Treatment with FA increased the levels of Ach-induced NO generation in the coronary artery of CBS-/+ mice. The results suggest that Ach induced coronary vasoconstriction in CBS-/+ mice and this vasoconstriction was ameliorated by FA treatment. The mechanisms for the impairment of vascular function and therapeutic effects of FA may be related to the regulation of eNOS expression, NO availability and tissue homocysteine.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
authors.forename: Natia
authors.initials: N
authors.lastname: Qipshidze
authors.forename: Naira
authors.initials: N
authors.lastname: Metreveli
authors.forename: David
authors.initials: D
authors.lastname: Lominadze
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology; D003329:Coronary Vasospasm / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004357:Drug Synergism; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D020138:Hyperhomocysteinemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014803:Vitamin B Complex / Q000494:pharmacology
chemical_list: D018679:Cholinergic Agonists; D014803:Vitamin B Complex; D005492:Folic Acid; D000109:Acetylcholine