TY - JOUR
T1 - Alterations in reactivity of small arterioles in rat skeletal muscle as a result of chronic ischaemia
AU - Kelsall, Christopher
AU - Brown, Margaret
AU - Hudlicka, Olga
PY - 2001/1/1
Y1 - 2001/1/1
N2 - In a model of chronic hind limb ischaemia, we examined whether impaired muscle blood flow, particularly during exercise, is partly due to modification of the reactivity of skeletal muscle resistance vessels by prolonged low blood flow. Two or 5 weeks after unilateral iliac artery ligation, terminal (A4) and preterminal (A3) arterioles of extensor digitorum longus muscle were viewed by intravital microscopy using epi-illumination, and diameter changes to topical application of endothelium-dependent (bradykinin, acetylcholine) and endothelium-independent (adenosine, sodium nitroprusside and noradrenaline) agonists measured. Chronic ischaemia had no effect on resting diameters of A3 or A4 vessels. Two weeks after ligation, dilation to bradykinin was attenuated by 75% for A3 and 50% for A4 arterioles (p <0.01 vs. control) and responses to acetylcholine were reversed from dilation to constriction (A3: control diameter change +29%, 2-week-ligated -17%; A4: control 18%, 2-week-ligated -13%). Five weeks after ligation, these effects were still apparent and, additionally, dilation to adenosine and sodium nitroprusside and constriction to noradrenaline were reduced. Thus, impaired dilation, most likely due to endothelial dysfunction, is an early manifestation of altered reactivity in the microcirculation of chronically ischaemic muscles, with functional impairment of vascular smooth muscle as a later consequence. These changes occurred despite modest improvements in muscle blood flow and perfusion pressure over the same time. These changes will act to the detriment of blood flow in contracting muscles and could limit the outcome of interventions to restore flow such as angioplasty or surgical bypass.
AB - In a model of chronic hind limb ischaemia, we examined whether impaired muscle blood flow, particularly during exercise, is partly due to modification of the reactivity of skeletal muscle resistance vessels by prolonged low blood flow. Two or 5 weeks after unilateral iliac artery ligation, terminal (A4) and preterminal (A3) arterioles of extensor digitorum longus muscle were viewed by intravital microscopy using epi-illumination, and diameter changes to topical application of endothelium-dependent (bradykinin, acetylcholine) and endothelium-independent (adenosine, sodium nitroprusside and noradrenaline) agonists measured. Chronic ischaemia had no effect on resting diameters of A3 or A4 vessels. Two weeks after ligation, dilation to bradykinin was attenuated by 75% for A3 and 50% for A4 arterioles (p <0.01 vs. control) and responses to acetylcholine were reversed from dilation to constriction (A3: control diameter change +29%, 2-week-ligated -17%; A4: control 18%, 2-week-ligated -13%). Five weeks after ligation, these effects were still apparent and, additionally, dilation to adenosine and sodium nitroprusside and constriction to noradrenaline were reduced. Thus, impaired dilation, most likely due to endothelial dysfunction, is an early manifestation of altered reactivity in the microcirculation of chronically ischaemic muscles, with functional impairment of vascular smooth muscle as a later consequence. These changes occurred despite modest improvements in muscle blood flow and perfusion pressure over the same time. These changes will act to the detriment of blood flow in contracting muscles and could limit the outcome of interventions to restore flow such as angioplasty or surgical bypass.
KW - ischaemia, chronic
KW - microscopy, intravital
KW - arterioles
KW - skeletal muscle
UR - http://www.scopus.com/inward/record.url?scp=0034962555&partnerID=8YFLogxK
U2 - 10.1159/000051049
DO - 10.1159/000051049
M3 - Article
C2 - 11399893
SN - 1423-0135
SN - 1423-0135
SN - 1423-0135
SN - 1423-0135
SN - 1423-0135
SN - 1423-0135
SN - 1423-0135
VL - 38
SP - 212
EP - 218
JO - Journal of Vascular Research
JF - Journal of Vascular Research
IS - 3
ER -