Age impairs Flk-1 signaling and NO-mediated vasodilation in coronary arterioles

Autor: Judy M. Muller-Delp, Amanda J. LeBlanc, Lori S. Kang, Robert D. Shipley
Rok vydání: 2008
Předmět:
Male
Vascular Endothelial Growth Factor A
Aging
Physiology
Vasodilator Agents
Vasodilation
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
Enos
Enzyme Inhibitors
Phosphorylation
Phosphoinositide-3 Kinase Inhibitors
biology
Age Factors
Articles
Coronary Vessels
Nitric oxide synthase
Arterioles
Hydrazines
NG-Nitroarginine Methyl Ester
medicine.anatomical_structure
Wortmannin
Cardiology and Cardiovascular Medicine
Blood Flow Velocity
Signal Transduction
medicine.medical_specialty
Nitric Oxide Synthase Type III
Endothelium
In Vitro Techniques
Nitric Oxide
Nitric oxide
Microcirculation
Coronary circulation
Arteriole
Coronary Circulation
Physiology (medical)
Internal medicine
medicine.artery
medicine
Animals
Nitric Oxide Donors
Dose-Response Relationship
Drug
biology.organism_classification
Vascular Endothelial Growth Factor Receptor-2
Acetylcholine
Rats
Androstadienes
Endocrinology
chemistry
Cinnamates
biology.protein
Stress
Mechanical
Proto-Oncogene Proteins c-akt
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 295:H2280-H2288
ISSN: 1522-1539
0363-6135
Popis: Impairment of flow-induced vasodilation in coronary resistance arterioles may contribute to the decline in coronary vasodilatory reserve that occurs with advancing age. This study investigated the effects of age on flow-induced signaling and activation of nitric oxide (NO)-mediated vasodilation in coronary resistance arterioles. Coronary arterioles were isolated from young (∼6 mo) and old (∼24 mo) male Fischer-344 rats to assess vasodilation to flow, vascular endothelial growth factor (VEGF), and ACh. Flow- and VEGF-induced vasodilation of coronary arterioles was impaired with age ( P ≤ 0.05); however, ACh-induced vasodilation was preserved with age. NG-nitro-l-arginine methyl ester (l-NAME) (1 × 10−5 M) eliminated vasodilation to flow, VEGF, and ACh, indicating dependence of these responses on NO. SU-1498, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR, also known as Flk-1), abolished age-related differences in flow-induced vasodilation. Flow-stimulated phosphorylation of Flk-1 in coronary arterioles from young but not old rats and Flk-1 protein was reduced in coronary arterioles from old rats compared with those from young rats. Flow stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) in coronary arterioles from both young and old rats. VEGF induced phosphorylation of both protein kinase B (Akt) and eNOS in coronary arterioles. VEGF-induced phosphorylation of Akt, but not eNOS, was significantly reduced in arterioles from old rats compared with arterioles from young rats. Wortmannin, an inhibitor of phosphatidylinositol (PI) 3-kinase, eliminated age-related differences in both flow- and VEGF-induced vasodilation. These results indicate that impairment of Flk-1/PI3-kinase signaling contributes to the reduction of flow-induced vasodilation in coronary arterioles with advancing age.
Databáze: OpenAIRE
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