Changes in capillary shear stress in skeletal muscles exposed to long-term activity: role of nitric oxide.
OBJECTIVE
The purpose of this study was to establish whether suppression of angiogenesis by nitric oxide synthase (NOS) inhibition in skeletal muscles exposed to long-term activity can be explained by changes in capillary shear stress linked to the lack of nitric oxide production.


METHODS
Capillary shear stress was calculated from diameters (d) and red blood cell velocities (V(rbc)) measured at rest and after acute contractions in epi-illuminated extensor digitorum longus muscles of control rats and those in which ankle flexors had been stimulated via implanted electrodes (10 Hz, 8 h x day(-1)) for 2 or 7 days without and with inhibition of nitric oxide synthase activity by N(omega)-nitro-L-arginine (L-NNA, 3-4 mg x day(-1) in drinking water).


RESULTS
Neither chronic electrical stimulation nor L-NNA treatment altered capillary diameters. Capillary V(rbc) and shear stress (SS) were doubled in muscles after 2 days stimulation (298 +/- 22 microm x s(-1) and 11.4 +/- 1.0 dyne x cm(-2), respectively, p < .005) compared to controls (148 +/- 18 microm x s(-1) and 5.6 +/- 0.8 dyne x cm(-2)) but normalized after 7 days (153 +/- 27 microm x s(-1) and 6.2 +/- 1.0 dyne x cm(-2)), when the capillary bed is known to be enlarged. L-NNA, which increased blood pressure in all treated animals, abolished the increase in capillary SS after 2 days stimulation and decreased SS after 7 days.


CONCLUSIONS
These data support a role for NO in the early elevation of capillary shear stress that initiates angiogenesis in stimulated muscles, likely via modulation of upstream vascular resistance, and could explain the lack of capillary growth in stimulated muscles when nitric oxide generation is suppressed.
Hudlicka
Olga
O
Department of Physiology, Charité-Universitatsmedizin Berlin, Campus Benjamin Franklin, Germany. o.hudlicka@bham.ac.uk
Brown
Margaret D
MD
May
Sylvia
S
Zakrzewicz
Andreas
A
Pries
Axel R
AR
D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002196:Capillaries / Q000502:physiology*; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical
D019335:Nitroarginine; D009569:Nitric Oxide