A causal role for endothelin-1 in the vascular adaptation to skeletal muscle deconditioning in spinal cord injury.
Publication year
2007Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 27, 2, (2007), pp. 325-31ISSN
Publication type
Article / Letter to editor
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Organization
Physiology
Intensive Care
Pharmacology-Toxicology
Internal Medicine
Former Organization
Pharmacology/Toxicology
Journal title
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
vol. 27
Issue
iss. 2
Page start
p. 325
Page end
p. 31
Subject
CTR 2: Clinical Pharmacology and physiology; IGMD 5: Health aging / healthy living; IGMD 7: Iron metabolism; N4i 1: Pathogenesis and modulation of inflammation; NCEBP 14: Cardiovascular diseases; UMCN 2.2: Vascular medicine and diabetesAbstract
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. METHODS AND 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.
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- Academic publications [238441]
- Electronic publications [122523]
- Faculty of Medical Sciences [90373]
- Open Access publications [97518]
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