Hyperhomocysteinemia evoked by folate depletion

Effects on coronary and carotid arterial function

J. David Symons, Adam E. Mullick, Jodi L. Ensunsa, Amy A. Ma, John C Rutledge

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

High circulating concentrations of homocysteine (ie, hyperhomocysteinemia [Hhcy]) impair the vascular function of peripheral conduit arteries and arterioles perfusing splanchnic and skeletal muscle regions. The effects of HHcy on coronary resistance vessel function and other indexes of vascular function, ie, arterial permeability and stiffening, are unclear. We tested the hypotheses that HHcy impairs coronary resistance vessel reactivity; increases carotid arterial permeability; and initiates arterial stiffening. Male rats that consumed folate-replete (CON, n=44) or folate-deplete (HHcy, n=48) chow for 4 to 5 weeks had total plasma homocysteine concentrations of 7±2 or 58±4 μmol/L, respectively. Maximal acetylcholine-evoked relaxation (≈40% vs ≈60%) and tension development from baseline in response to nitric oxide synthase inhibition (≈20% vs ≈40%) were lower (both P<0.05) in coronary resistance vessels (≈120 μm, internal diameter) isolated from HHcy versus CON animals, respectively, whereas sodium nitroprusside-evoked relaxation and contractile responses to serotonin and potassium chloride were similar between groups. Permeability to 4400 MW and 65 000 MW fluorescently labeled (TRITC) dextran reference macromolecules (quantitative fluorescence microscopy) was ≈44% and ≈24% greater (P<0.05), respectively, in carotid arteries from HHcy versus CON rats. Maximal strain, evaluated by using a vessel elastigraph, was less (≈32% vs 42%, P<0.05) in carotid arterial segments from HHcy versus CON animals, respectively. Finally, estimates of oxidative (copperzinc+manganese superoxide dismutase activity) and glycoxidative (pentosidine) stress were elevated (P<0.05) in arterial tissue from HHcy versus CON rats. These findings suggest that moderately severe HHcy evoked by folate-depletion impairs endothelium-dependent relaxation of coronary resistance vessels, increases carotid arterial permeability, and initiates arterial stiffening. HHcy may produce these effects by a mechanism associated with increased oxidative and glycoxidative stress.

Original languageEnglish (US)
Pages (from-to)772-780
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number5
DOIs
StatePublished - 2002

Fingerprint

Hyperhomocysteinemia
Folic Acid
Permeability
Coronary Vessels
Homocysteine
Blood Vessels
Viscera
Potassium Chloride
Arterioles
Nitroprusside
Dextrans
Carotid Arteries
Fluorescence Microscopy
Nitric Oxide Synthase
Acetylcholine
Superoxide Dismutase
Endothelium
Serotonin
Skeletal Muscle
Oxidative Stress

Keywords

  • Arterial permeability
  • Arterial stiffness
  • Coronary resistance artery
  • Rat
  • Vascular reactivity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Hyperhomocysteinemia evoked by folate depletion : Effects on coronary and carotid arterial function. / Symons, J. David; Mullick, Adam E.; Ensunsa, Jodi L.; Ma, Amy A.; Rutledge, John C.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 22, No. 5, 2002, p. 772-780.

Research output: Contribution to journalArticle

Symons, J. David ; Mullick, Adam E. ; Ensunsa, Jodi L. ; Ma, Amy A. ; Rutledge, John C. / Hyperhomocysteinemia evoked by folate depletion : Effects on coronary and carotid arterial function. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2002 ; Vol. 22, No. 5. pp. 772-780.
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