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 language | English (US) |
|---|---|
| Pages (from-to) | 772-780 |
| Number of pages | 9 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 22 |
| Issue number | 5 |
| DOIs | |
| State | Published - 2002 |
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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 journal › Article
}
TY - JOUR
T1 - Hyperhomocysteinemia evoked by folate depletion
T2 - Effects on coronary and carotid arterial function
AU - Symons, J. David
AU - Mullick, Adam E.
AU - Ensunsa, Jodi L.
AU - Ma, Amy A.
AU - Rutledge, John C
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Arterial permeability
KW - Arterial stiffness
KW - Coronary resistance artery
KW - Rat
KW - Vascular reactivity
UR - http://www.scopus.com/inward/record.url?scp=0036091558&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036091558&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.0000014588.71807.0A
DO - 10.1161/01.ATV.0000014588.71807.0A
M3 - Article
C2 - 12006389
AN - SCOPUS:0036091558
VL - 22
SP - 772
EP - 780
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 5
ER -