期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 289, 期 2, 页码 H947-H959出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00952.2004
关键词
dopamine beta-hydroxylase; arteriogenesis; laser-Doppler imaging
资金
- NHLBI NIH HHS [T32-HL-069768, HL-62584] Funding Source: Medline
Catecholamine stimulation of alpha(1)-adrenoceptors exerts growth factor-like activity, mediated by generation of reactive oxygen species, on arterial smooth muscle cells and adventitial fibroblasts and contributes to hypertrophy and hyperplasia in models of vascular injury and disease. Adrenergic trophic activity also contributes to flow-mediated positive arterial remodeling by augmenting proliferation and leukocyte accumulation. To further examine this concept, we studied whether catecholamines contribute to collateral growth and angiogenesis in hindlimb insufficiency. Support for this hypothesis includes the above-mentioned studies, evidence that ischemia augments norepinephrine release from sympathetic nerves, and proposed involvement of reactive oxygen species in angiogenesis and collateral growth. Mice deficient in catecholamine synthesis [by gene deletion of dopamine beta-hydroxylase (DBH-/-)] were studied. At 3 wk after femoral artery ligation, increases in adductor muscle perfusion were similar in DBH-/- and wild-type mice, whereas recovery of plantar perfusion and calf microsphere flow were attenuated, although not significantly. Preexisting collaterals in adductor of wild-type mice showed increases in lumen diameter (60%) and medial and adventitial thickness (57 and 119%, P < 0.05 here and below). Lumen diameter increased similarly in DBH-/- mice (52%); however, increases in medial and adventitial thicknesses were reduced (30 and 65%). Leukocyte accumulation in the adventitia/periadventitia of collaterals was 39% less in DBH-/- mice. Increased density of alpha-smooth muscle actin-positive vessels in wild-type adductor (45%) was inhibited in DBH-/- mice (2%). Although both groups experienced similar atrophy in the gastrocnemius (similar to 22%), the increase in capillary-to-muscle fiber ratio in wild-type mice (21%) was inhibited in DBH-/- mice (7%). These data suggest that catecholamines may contribute to collateral growth and angiogenesis in tissue ischemia.
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