title: Physiological adjustments and arteriolar remodelling within skeletal muscle during acclimation to chronic hypoxia in the rat.
abstract: 1. We have investigated the physiological and structural changes that occur in skeletal muscle vasculature during acclimation to chronic hypoxia in rats exposed to 12 % O2 in a hypoxic chamber for 7 or 18 days (7CH and 18CH rats, respectively) and in age-matched normoxic (7N and 18N) rats. 2. Under anaesthesia and breathing 12 % O2, 7CH and 18CH rats had lower arterial blood pressure (ABP) than 7N and 18N rats breathing air, but the haematocrit of the CH rats was increased so that their arterial O2 content equalled that of N rats. Blood flow recorded from the iliac or femoral artery and used to compute muscle vascular conductance (MVC: blood flow/ABP) showed that, in 18CH rats, MVC was comparable with that of 18N rats. 3. Maximal MVC induced by infusion of sodium nitroprusside (SNP) was used as an index of structural vascular conductance and compared with the MVC evoked by acute hypoxia (breathing 8 % O2). Hypoxia induced similar increases in MVC in 7N and 7CH rats and in 18N and 18CH rats, even though N rats were switched from air to 8 % O2 and CH rats were switched from 12 to 8 % O2. The MVCs attained with 8 % O2 and SNP were similar in 7N and 18N rats. However, the MVCs attained with 8 % O2 in 7CH and 18CH rats were only approximately 60 % of those evoked by SNP, while the MVC attained with SNP was greater in 18CH than in 18N rats. 4. Vascular casts of the spinotrapezius muscle analysed ex vivo showed that interbranch intervals along primary, secondary and terminal arterioles (22-50, 13-18 and 7-13 microm diameter, respectively) were 30-50 % shorter in 7CH and 18CH rats than in 7N and 18N rats. Further, the proportions of branches that were of the secondary and terminal arteriolar categories were increased such that the mean diameter of the branches was lower in 7CH than in 7N rats and lower in 18CH than in 18N rats. 5. These results indicate that arteriolar remodelling and angiogenesis occurs in skeletal muscle during acclimation to chronic hypoxia, beginning by the 7th day and progressing at least until the 18th day, so that the number of small arterioles and the functional size of the vascular bed is increased. We propose that these structural and functional changes enhance the ability of skeletal muscle to respond to acute hypoxia by facilitating the increase in vascular conductance, blood flow and thereby the O2 that can be delivered to muscle.
authors.affiliation: Department of Physiology, The Medical School, Birmingham B15 2TT, UK.
authors.forename: K
authors.initials: K
authors.lastname: Smith
authors.forename: J M
authors.initials: JM
authors.lastname: Marshall
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000503:physiopathology*; D009389:Neovascularization, Pathologic; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D009599:Nitroprusside