Preserved contribution of nitric oxide to baseline vascular tone in deconditioned human skeletal muscle

Bleeker, Michiel W. P.; Kooijman, M. A. P.; Rongen, Gerard A.; Hopman, Maria T. E.; Smits, Paul

doi:10.1113/jphysiol.2005.085936

Cited by 28 publications

(52 citation statements)

References 53 publications

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“…Moreover, because ET-receptor blockade eliminates the difference in leg blood flow between SCI and control subjects, ET-1 may even be primarily responsible for the increased basal leg vascular tone in SCI. This agrees with previous studies from our department which excluded a role for nitric oxide 16 or for ␣-adrenergic receptor-mediated effects 17 in the elevated leg vascular tone in SCI individuals. Apart from the sympathetic denervation, the main difference between SCI individuals and controls is the paralysis of the legs, resulting in an extreme inactivity of the legs.…”

Section: February 2007supporting

confidence: 82%

“…2 We recently demonstrated that the contribution of NO to baseline leg vascular tone is preserved in SCI subjects as examined with infusion of L-NMMA in the femoral artery. 16 Because the vasodilator properties induced by agonism of the ET B -receptors are mediated by NO, the ET B -receptor cannot account for the increased ET-1-mediated vasoconstriction observed in the legs of SCI subjects. Because both groups were sex-matched, each population consisted of 7 males and 1 female.…”

Section: February 2007mentioning

confidence: 99%

“…This cannula was used for the intra-arterial administration of ET-receptor antagonists by an automatic syringe infusion pump (Type P4000, Welmed Ltd) 16,17 and for blood pressure measurement (Type PX600, Edwards Lifesciences Services GmbH). Heart rate was recorded from the ECG.…”

Section: Protocolmentioning

confidence: 99%

“…Previous research demonstrated that extensive vascular adaptations, such as an increased leg vascular tone, occur in the inactive and paralyzed legs of spinal cord-injured individuals. 15 These adaptations cannot be explained by a reduced availability of nitric oxide 16 or adaptations in the ␣-adrenergic tone. 17 According to our hypothesis, the increased vascular tone in the deconditioned legs of spinal cord-injured individuals is caused by an augmented contribution of ET-1.…”

mentioning

confidence: 99%

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A Causal Role for Endothelin-1 in the Vascular Adaptation to Skeletal Muscle Deconditioning in Spinal Cord injury

Thijssen

Ellenkamp

Kooijman

et al. 2007

ATVB

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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 (nϭ4), 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%, PϽ0.05), indicating a small contribution of ET-1 to leg vascular tone. In SCI, baseline blood flow was lower compared with controls (Pϭ0.05). In SCI, dual ET-receptor blockade increased blood flow (41%, PϽ0.001). This vasodilator response was significantly larger in SCI compared with controls (PϽ0.001). 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%, Pϭ0.04). Key Words: endothelin receptor Ⅲ endothelium Ⅲ exercise Ⅲ cardiovascular disease Ⅲ paraplegia T he endothelium plays an important role in the regulation of vascular tone via the release of vasodilator and vasoconstrictor substances. Endothelin-1 (ET-1) 1 is one of the most potent endothelium-derived constricting factors, and contributes to the regulation of peripheral vascular tone 2,3 by interacting with ET A -4 and ET B -receptors 5 on smooth muscle and endothelial cells. 6,7 In several pathological conditions, such as pulmonary 8 and systemic essential hypertension, 9 heart failure, 10,11 atherosclerosis, and obesity, 12 ET-1 plasma levels are elevated and contribute to the increased vascular tone observed in these disease states. In models of skeletal muscle deconditioning, such as unilateral limb suspension 13 and bed rest, 14 vascular tone is also increased. In the present study, we hypothesize that the elevated vascular tone in deconditioned muscles can be explained by an augmented contribution of ET-1. Conclusion-ET-1 mediates the increased vascular tone of extremely inactive legs of SCI individuals by increased activation of ETIndividuals with a spinal cord injury offer a unique model of nature to assess peripheral vascular adaptations to inactivity because the skeletal muscles below the level of the lesion are paralyzed and, therefore, extremely inactive. Previous research demonstrated that extensive vascular adaptations, such as an increased leg vascular tone, occur in the inactive and paralyzed legs of spinal cord-injured individuals. 15 These adaptation...

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Section: February 2007supporting

confidence: 82%

Section: February 2007mentioning

confidence: 99%

Section: Protocolmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

A Causal Role for Endothelin-1 in the Vascular Adaptation to Skeletal Muscle Deconditioning in Spinal Cord injury

Thijssen

Ellenkamp

Kooijman

et al. 2007

ATVB

Self Cite

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“…NO is synthesized in vivo from the amino acid Larginine and oxygen by NO synthase (NOS), an enzyme that occurs in 3 distinct isoforms (9)(10)(11) (12)(13)(14). A limitation of L-NMMA is that it does not fully inhibit NOS activity and, thus, partially preserves NO synthesis.…”

Section: Introductionmentioning

confidence: 99%

Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular Function in Chronic Tetraplegia

Fountaine

Radulovic

Cardozo

et al. 2009

The Journal of Spinal Cord Medicine

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Background/Objective: To improve our understanding of the lower-leg vascular responses of nitric oxide synthase inhibition in persons with tetraplegia. Participants: Six people with chronic tetraplegia and 6 age-matched controls. Methods: Lower-leg relative vascular resistance and venous volume variation were obtained by venous occlusion plethysmography and blood pressure by auscultation at baseline. Postintravenous infusion of the nitric oxide synthase inhibitor N G -nitro-L-arginine-methyl-ester (1 mg?kg 21) or placebo on separate days. Results: At baseline in the group with tetraplegia compared with controls, mean arterial pressure and relative vascular resistance of the leg were significantly lower. After nitric oxide synthase inhibition, mean arterial pressure and lower leg vascular resistance were significantly elevated in both groups. There were no group or intervention differences in venous volume variation. Conclusion: These preliminary results suggest that nitric oxide synthase inhibition with 1 mg?kg 21 N G -nitro-L-arginine-methyl-ester normalizes seated blood pressure and lower leg vascular resistance to control group baseline levels.

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Single‐leg disuse decreases skeletal muscle strength, size, and power in uninjured adults: A systematic review and meta‐analysis

Preobrazenski

Seigel

Halliday

et al. 2023

J cachexia sarcopenia muscle

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We aimed to quantify declines from baseline in lower limb skeletal muscle size and strength of uninjured adults following single‐leg disuse. We searched EMBASE, Medline, CINAHL, and CCRCT up to 30 January 2022. Studies were included in the systematic review if they (1) recruited uninjured participants; (2) were an original experimental study; (3) employed a single‐leg disuse model; and (4) reported muscle strength, size, or power data following a period of single‐leg disuse for at least one group without a countermeasure. Studies were excluded if they (1) did not meet all inclusion criteria; (2) were not in English; (3) reported previously published muscle strength, size, or power data; or (4) could not be sourced from two different libraries, repeated online searches, and the authors. We used the Cochrane Risk of Bias Assessment Tool to assess risk of bias. We then performed random‐effects meta‐analyses on studies reporting measures of leg extension strength and extensor size. Our search revealed 6548 studies, and 86 were included in our systematic review. Data from 35 and 20 studies were then included in the meta‐analyses for measures of leg extensor strength and size, respectively (40 different studies). No meta‐analysis for muscle power was performed due to insufficient homogenous data. Effect sizes (Hedges' gav) with 95% confidence intervals for leg extensor strength were all durations = −0.80 [−0.92, −0.68] (n = 429 participants; n = 68 aged 40 years or older; n ≥ 78 females); ≤7 days of disuse = −0.57 [−0.75, −0.40] (n = 151); >7 days and ≤14 days = −0.93 [−1.12, −0.74] (n = 206); and >14 days = −0.95 [−1.20, −0.70] (n = 72). Effect sizes for measures of leg extensor size were all durations = −0.41 [−0.51, −0.31] (n = 233; n = 32 aged 40 years or older; n ≥ 42 females); ≤7 days = −0.26 [−0.36, −0.16] (n = 84); >7 days and ≤14 days = −0.49 [−0.67, −0.30] (n = 102); and >14 days = −0.52 [−0.74, −0.30] (n = 47). Decreases in leg extensor strength (cast: −0.94 [−1.30, −0.59] (n = 73); brace: −0.90 [−1.18, −0.63] (n = 106)) and size (cast: −0.61[−0.87, −0.35] (n = 41); brace: (−0.48 [−1.04, 0.07] (n = 41)) following 14 days of disuse did not differ for cast and brace disuse models. Single‐leg disuse in adults resulted in a decline in leg extensor strength and size that reached a nadir beyond 14 days. Bracing and casting led to similar declines in leg extensor strength and size following 14 days of disuse. Studies including females and males and adults over 40 years of age are lacking.

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Preserved contribution of nitric oxide to baseline vascular tone in deconditioned human skeletal muscle

Cited by 28 publications

References 53 publications

A Causal Role for Endothelin-1 in the Vascular Adaptation to Skeletal Muscle Deconditioning in Spinal Cord injury

A Causal Role for Endothelin-1 in the Vascular Adaptation to Skeletal Muscle Deconditioning in Spinal Cord injury

Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular Function in Chronic Tetraplegia

Single‐leg disuse decreases skeletal muscle strength, size, and power in uninjured adults: A systematic review and meta‐analysis

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