title: A causal role for endothelin-1 in the vascular adaptation to skeletal muscle deconditioning in spinal cord injury.
abstract: OBJECTIVE
  Endothelin-1 (ET-1) contributes to the increased peripheral resistance in heart failure and hypertension. Physical inactivity is associated with cardiovascular disease and characterized by increased vascular tone. In this study, we assess the contribution of ET-1 to the increased vascular tone in the extremely deconditioned legs of spinal cord-injured (SCI) individuals before and after exercise training.
  
  
  RESULTS
  In 8 controls and 8 SCI individuals, bilateral thigh blood flow was measured by plethysmography before and during the administration of an ET(A)/ET(B)-receptor blocker into the femoral artery. In SCI, this procedure was repeated after 6 weeks of electro-stimulated training. In a subset of SCI (n=4), selective ET(A)-receptor blockade was performed to determine the role of the ET(A)-receptors. In controls, dual ET-receptor blockade increased leg blood flow at the infused side (10%, P<0.05), indicating a small contribution of ET-1 to leg vascular tone. In SCI, baseline blood flow was lower compared with controls (P=0.05). In SCI, dual ET-receptor blockade increased blood flow (41%, P<0.001). This vasodilator response was significantly larger in SCI compared with controls (P<0.001). The response to selective ET(A)-receptor blockade was similar to the effect of dual blockade. Electro-stimulated training normalized baseline blood flow in SCI and reduced the response to dual ET-receptor blockade in the infused leg (29%, P=0.04).
  
  
  CONCLUSIONS
  ET-1 mediates the increased vascular tone of extremely inactive legs of SCI individuals by increased activation of ET(A)-receptors. Physical training reverses the ET-1-pathway, which normalizes basal leg vascular tone.
authors.affiliation: Department of Physiology, Institute of Fundamental and Clinical Movement Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein-Noord 21, 6525 EZ, Nijmegen, The Netherlands.
authors.forename: Dick H J
authors.initials: DH
authors.lastname: Thijssen
authors.forename: Reinier
authors.initials: R
authors.lastname: Ellenkamp
authors.forename: Miriam
authors.initials: M
authors.lastname: Kooijman
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Rongen
authors.forename: Maria T E
authors.initials: MT
authors.lastname: Hopman
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology; D016022:Case-Control Studies; D004599:Electric Stimulation Therapy; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000097:blood / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D009133:Muscular Atrophy / Q000503:physiopathology*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D044022:Receptor, Endothelin A / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology* / Q000534:rehabilitation*; D014664:Vasodilation / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)