Evidence for impaired neurovascular transmission in a murine model of Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a muscle-wasting disease caused by mutations in the dystrophin gene. Little is known about how blood flow control is affected in arteriolar networks supplying dystrophic muscle. We tested the hypothesis that mdx mice, a murine model for DMD, exhibit defects in arteriolar vasomotor control. The cremaster muscle was prepared for intravital microscopy in pentobarbital sodium-anesthetized mdx and C57BL/10 control mice (n ≥ 5 per group). Spontaneous vasomotor tone increased similarly with arteriolar branch order in both mdx and C57BL/10 mice [pooled values: first order (1A), 6%; second order (2A), 56%; and third order (3A), 61%] with no difference in maximal diameters between groups measured during equilibration with topical 10 μM sodium nitroprusside (pooled values: 1A, 70 ± 3 μm; 2A, 31 ± 3 μm; and 3A, 19 ± 3 μm). Concentration-response curves to acetylcholine (ACh) and norepinephrine added to the superfusion solution did not differ between mdx and C57BL/10 mice, nor did constriction to elevated (21%) oxygen. In response to local stimulation from a micropipette, conducted vasodilation to ACh and conducted vasoconstriction to KCl were also not different between groups; however, constriction decayed with distance (P < 0.05) whereas dilation did not. Remarkably, arteriolar constriction to perivascular nerve stimulation (PNS) at 2, 4, and 8 Hz was reduced by ∼25-30% in mdx mice compared with C57BL/10 mice (P < 0.05). With intact arteriolar reactivity to agonists, attenuated constriction to perivascular nerve stimulation indicates impaired neurovascular transmission in arterioles controlling blood flow in mdx mice.
Dept. of Medical Pharmacology and Physiology, MA415 Medical Science Bldg., Univ. of Missouri-Columbia, Columbia, MO 65212, USA.
Pooneh
P
Bagher
Dongsheng
D
Duan
Steven S
SS
Segal
D000818:Animals; D001160:Arterioles / Q000503:physiopathology*; D001783:Blood Flow Velocity; D006801:Humans; D051379:Mice; D018101:Mice, Inbred mdx; D008833:Microcirculation; D018482:Muscle, Skeletal / Q000098:blood supply / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000503:physiopathology*; D014666:Vasomotor System / Q000503:physiopathology*