Alterations in reactivity of small arterioles in rat skeletal muscle as a result of chronic ischaemia

In a model of chronic hind limb ischaemia, we examined whether impaired mus cle blood flow, particularly during exercise, is partly due to modification of the reactivity of skeletal muscle resistance vessels by prolonged low b lood flow. Two or 5 weeks after unilateral iliac artery ligation, terminal (A4) and preterminal (A3) arterioles of extensor digitorum longus muscle we re viewed by intravital microscopy using epi-illumination, and diameter cha nges to topical application of endothelium-dependent (bradykinin, acetylcho line) and endothelium-independent (adenosine, sodium nitroprusside and nora drenaline) agonists measured. Chronic ischaemia had no effect on resting di ameters of A3 or A4 vessels. Two weeks after ligation, dilation to bradykin in was attenuated by 75% for A3 and 50% for A4 arterioles (p < 0.01 vs. con trol) and responses to acetylcholine were reversed from dilation to constri ction (A3: control diameter change +29%, 2-week-ligated -17%; A4: control 1 8%, 2-week-ligated -13%). Five weeks after ligation, these effects were sti ll apparent and, additionally, dilation to adenosine and sodium nitroprussi de and constriction to noradrenaline were reduced. Thus, impaired dilation, most likely due to endothelial dysfunction, is an early manifestation of a ltered reactivity in the microcirculation of chronically ischaemic muscles, with functional impairment of vascular smooth muscle as a later consequenc e. These changes occurred despite modest improvements in muscle blood flow and perfusion pressure over the same time. These changes will act to the de triment of blood flow in contracting muscles and could limit the outcome of interventions to restore flow such as angioplasty or surgical bypass. Copyright <(c)> 2001 S. Karger AG, Basal.