title: Phenotype of capillaries in skeletal muscle of nNOS-knockout mice.
abstract: Because neuronal nitric oxide synthase (nNOS) has a well-known impact on arteriolar blood flow in skeletal muscle, we compared the ultrastructure and the hemodynamics of/in the ensuing capillaries in the extensor digitorum longus (EDL) muscle of male nNOS-knockout (KO) mice and wild-type (WT) littermates. The capillary-to-fiber (C/F) ratio (-9.1%) was lower (P ≤ 0.05) in the nNOS-KO mice than in the WT mice, whereas the mean cross-sectional fiber area (-7.8%) and the capillary density (-3.1%) varied only nonsignificantly (P > 0.05). Morphometrical estimation of the area occupied by the capillaries as well as the volume and surface densities of the subcellular compartments differed nonsignificantly (P > 0.05) between the two strains. Intravital microscopy revealed neither the capillary diameter (+3% in nNOS-KO mice vs. WT mice) nor the mean velocity of red blood cells in EDL muscle (+25% in nNOS-KO mice vs. WT mice) to significantly vary (P > 0.05) between the two strains. The calculated shear stress in the capillaries was likewise nonsignificantly different (3.8 ± 2.2 dyn/cm² in nNOS-KO mice and 2.1 ± 2.2 dyn/cm² in WT mice; P > 0.05). The mRNA levels of vascular endothelial growth factor (VEGF)-A were lower in the EDL muscle of nNOS-KO mice than in the WT littermates (-37%; P ≤ 0.05), whereas mRNA levels of VEGF receptor-2 (VEGFR-2) (-11%), hypoxia inducible factor-1α (+9%), fibroblast growth factor-2 (-14%), and thrombospondin-1 (-10%) differed nonsignificantly (P > 0.05). Our findings support the contention that VEGF-A mRNA expression and C/F-ratio but not the ultrastructure or the hemodynamics of/in capillaries in skeletal muscle at basal conditions depend on the expression of nNOS.
authors.affiliation: Institute of Anatomy, University of Bern, Bern, Switzerland. oliver.baum@ana.unibe.ch
authors.forename: Oliver
authors.initials: O
authors.lastname: Baum
authors.forename: Max
authors.initials: M
authors.lastname: Vieregge
authors.forename: Pascale
authors.initials: P
authors.lastname: Koch
authors.forename: Safak
authors.initials: S
authors.lastname: Gül
authors.forename: Sabine
authors.initials: S
authors.lastname: Hahn
authors.forename: Felicitas A M
authors.initials: FA
authors.lastname: Huber-Abel
authors.forename: Axel R
authors.initials: AR
authors.lastname: Pries
authors.forename: Hans
authors.initials: H
authors.lastname: Hoppeler
mesh_terms: D000818:Animals; D002196:Capillaries / Q000502:physiology* / Q000648:ultrastructure*; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I
keywords: capillary ultrastructure; intravital microscopy; neuronal nitric oxide synthase; skeletal muscle; vascular endothelial growth factor-A gene expression