Short-duration increases in intraluminal pressure improve vasoconstrictor responses in aged skeletal muscle feed arteries

We tested the hypothesis that aging decreases endothelium-dependent vasodilation in feed arteries perfusing rat skeletal muscle. In addition, we tested the hypothesis that attenuated vasodilator responses are associated with decreased endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) expression. Soleus feed arteries (SFA) and gastrocnemius feed arteries (GFA) were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats. Feed arteries from the right hindlimb were cannulated with two glass micropipettes for examination of endothelium-dependent [acetylcholine (ACh)] and endothelium-independent [adenosine (Ado) or sodium nitroprusside (SNP)] vasodilator function. Feed arteries from the left hindlimb were frozen and used to assess eNOS and SOD-1 protein and mRNA expression. In SFA, endothelium-dependent dilation to ACh was reduced in old rats (0.9 ± 0.04 vs. 0.8 ± 0.03), whereas dilator responses to Ado and SNP were similar in SFA of young and old rats. In GFA, vasodilator responses to ACh, Ado, and SNP were not altered by age. eNOS and SOD-1 protein expression declined with age in SFA (−71 and −54%, respectively) but not in GFA. eNOS and SOD-1 mRNA expression were not altered by age in SFA or GFA. Collectively, these data indicate aging induces muscle-specific impairment of endothelium-dependent vascular function in SFA.

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Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. I. Impact of obesity

Journal of Applied Physiology ◽

10.1152/japplphysiol.01233.2013 ◽

2014 ◽

Vol 116 (8) ◽

pp. 1017-1032 ◽

Cited By ~ 19

Author(s):

Nathan T. Jenkins ◽

Jaume Padilla ◽

Pamela K. Thorne ◽

Jeffrey S. Martin ◽

R. Scott Rector ◽

...

Keyword(s):

Skeletal Muscle ◽

Endothelial Cell ◽

Rna Sequencing ◽

Differentially Expressed ◽

Aortic Endothelial Cell ◽

Oletf Rats ◽

Long Evans ◽

Feed Arteries ◽

Skeletal Muscle Feed Arteries ◽

Aortic Endothelial

We employed next-generation RNA sequencing (RNA-Seq) technology to determine the influence of obesity on global gene expression in skeletal muscle feed arteries. Transcriptional profiles of the gastrocnemius and soleus muscle feed arteries (GFA and SFA, respectively) and aortic endothelial cell-enriched samples from obese Otsuka Long-Evans Tokushima Fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats were examined. Obesity produced 282 upregulated and 133 downregulated genes in SFA and 163 upregulated and 77 downregulated genes in GFA [false discovery rate (FDR) < 10%] with an overlap of 93 genes between the arteries. In LETO rats, there were 89 upregulated and 114 downregulated genes in the GFA compared with the SFA. There were 244 upregulated and 275 downregulated genes in OLETF rats (FDR < 10%) in the GFA compared with the SFA, with an overlap of 76 differentially expressed genes common to both LETO and OLETF rats in both the GFA and SFA. A total of 396 transcripts were found to be differentially expressed between LETO and OLETF in aortic endothelial cell-enriched samples. Overall, we found 1) the existence of heterogeneity in the transcriptional profile of the SFA and GFA within healthy LETO rats, 2) that this between-vessel heterogeneity was markedly exacerbated in the hyperphagic, obese OLETF rat, and 3) a greater number of genes whose expression was altered by obesity in the SFA compared with the GFA. Also, results indicate that in OLETF rats the GFA takes on a relatively more proatherogenic phenotype compared with the SFA.

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Vasodilatory function in human skeletal muscle feed arteries with advancing age: the role of adropin

The Journal of Physiology ◽

10.1113/jp277410 ◽

2019 ◽

Vol 597 (7) ◽

pp. 1791-1804 ◽

Cited By ~ 4

Author(s):

Oh Sung Kwon ◽

Robert H. I. Andtbacka ◽

John R. Hyngstrom ◽

Russell S. Richardson

Keyword(s):

Skeletal Muscle ◽

Human Skeletal Muscle ◽

Vasodilatory Function ◽

Feed Arteries ◽

Skeletal Muscle Feed Arteries

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The Role of TRPV Ion Channels in Heat-induced Sympatholysis of Human Skeletal Muscle Feed Arteries

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000494172.87916.81 ◽

2014 ◽

Vol 46 ◽

pp. 328-329

Author(s):

Jayson R. Gifford ◽

Stephen J. Ives ◽

Song Y. Park ◽

Robert H.I. Andtbacka ◽

Joel D. Trinity ◽

...

Keyword(s):

Skeletal Muscle ◽

Ion Channels ◽

Human Skeletal Muscle ◽

Feed Arteries ◽

Skeletal Muscle Feed Arteries

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Heat and α1-adrenergic responsiveness in human skeletal muscle feed arteries: the role of nitric oxide

Journal of Applied Physiology ◽

10.1152/japplphysiol.00955.2012 ◽

2012 ◽

Vol 113 (11) ◽

pp. 1690-1698 ◽

Cited By ~ 19

Author(s):

Stephen J. Ives ◽

Robert H. I. Andtbacka ◽

Sun Hyung Kwon ◽

Yan-Ting Shiu ◽

Ting Ruan ◽

...

Keyword(s):

Nitric Oxide ◽

Skeletal Muscle ◽

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Human Skeletal Muscle ◽

Bovine Endothelial Cells ◽

No Bioavailability ◽

Feed Arteries ◽

Skeletal Muscle Feed Arteries

Increased local temperature exerts a sympatholytic effect on human skeletal muscle feed arteries. We hypothesized that this attenuated α1-adrenergic receptor responsiveness may be due to a temperature-induced increase in nitric oxide (NO) bioavailability, thereby reducing the impact of the α1-adrenergic receptor agonist phenylephrine (PE). Thirteen human skeletal muscle feed arteries were harvested, and wire myography was used to generate PE concentration-response curves at 37°C and 39°C, with and without the NO synthase (NOS) inhibitor NG-monomethyl-l-arginine (l-NMMA). A subset of arteries ( n = 4) were exposed to 37°C or 39°C, and the protein content of endothelial NOS (eNOS) and α1-adrenergic receptors was determined by Western blot analysis. Additionally, cultured bovine endothelial cells were exposed to static or shear stress conditions at 37°C and 39°C and assayed for eNOS activation (phosphorylation at Ser1177), eNOS expression, and NO metabolites [nitrate + nitrite (NOx)]. Maximal PE-induced vasocontraction (PEmax) was lower at 39°C than at 37°C [39 ± 10 vs. 84 ± 30% maximal response to 100 mM KCl (KClmax)]. NO blockade restored vasocontraction at 39°C to that achieved at 37°C (80 ± 26% KClmax). Western blot analysis of the feed arteries revealed that heating increased eNOS protein, but not α1-adrenergic receptors. Heating of bovine endothelial cells resulted in greater shear stress-induced eNOS activation and NOx production. Together, these data reveal for the first time that, in human skeletal muscle feed arteries, NO blockade can restore the heat-attenuated α1-adrenergic receptor-mediated vasocontraction and implicate endothelium-derived NO bioavailability as a major contributor to heat-induced sympatholysis. Consequently, these findings highlight the important role of vasodilators in modulating the vascular response to vasoconstrictors.

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Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. II. Impact of exercise training in obesity

Journal of Applied Physiology ◽

10.1152/japplphysiol.01234.2013 ◽

2014 ◽

Vol 116 (8) ◽

pp. 1033-1047 ◽

Cited By ~ 19

Author(s):

Jaume Padilla ◽

Nathan T. Jenkins ◽

Pamela K. Thorne ◽

Jeffrey S. Martin ◽

R. Scott Rector ◽

...

Keyword(s):

Skeletal Muscle ◽

Endothelial Cells ◽

Exercise Training ◽

Training Program ◽

Rna Sequencing ◽

Gastrocnemius Muscle ◽

Aortic Endothelial Cells ◽

Feed Arteries ◽

Skeletal Muscle Feed Arteries ◽

Aortic Endothelial

We employed next-generation RNA sequencing (RNA-Seq) technology to determine the extent to which exercise training alters global gene expression in skeletal muscle feed arteries and aortic endothelial cells of obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Transcriptional profiles of the soleus and gastrocnemius muscle feed arteries (SFA and GFA, respectively) and aortic endothelial cell-enriched samples from rats that underwent an endurance exercise training program (EndEx; n = 12) or a interval sprint training program (IST; n = 12) or remained sedentary (Sed; n = 12) were examined. In response to EndEx, there were 39 upregulated (e.g., MANF) and 20 downregulated (e.g., ALOX15) genes in SFA and 1 upregulated (i.e., Wisp2) and 1 downregulated (i.e., Crem) gene in GFA [false discovery rate (FDR) < 10%]. In response to IST, there were 305 upregulated (e.g., MANF, HSPA12B) and 324 downregulated genes in SFA and 101 upregulated and 66 downregulated genes in GFA, with an overlap of 32 genes between arteries. Furthermore, in aortic endothelial cells, there were 183 upregulated (e.g., eNOS, SOD-3) and 141 downregulated (e.g., ATF3, Clec1b, npy, leptin) genes with EndEx and 71 upregulated and 69 downregulated genes with IST, with an overlap of 35 between exercise programs. Expression of only two genes (Tubb2b and Slc9a3r2) was altered (i.e., increased) by exercise in all three arteries. The finding that both EndEx and IST produced greater transcriptional changes in the SFA compared with the GFA is intriguing when considering the fact that treadmill bouts of exercise are associated with greater relative increases in blood flow to the gastrocnemius muscle compared with the soleus muscle.

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Vascular Smooth Muscle Contractile Function Declines With Age in Skeletal Muscle Feed Arteries

Frontiers in Physiology ◽

10.3389/fphys.2018.00856 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 5

Author(s):

John W. Seawright ◽

Harini Sreenivasappa ◽

Holly C. Gibbs ◽

Samuel Padgham ◽

Song Y. Shin ◽

...

Keyword(s):

Skeletal Muscle ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Contractile Function ◽

Feed Arteries ◽

Muscle Contractile ◽

Skeletal Muscle Feed Arteries

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α1- and α2-Adrenergic responsiveness in human skeletal muscle feed arteries: the role of TRPV ion channels in heat-induced sympatholysis

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00068.2014 ◽

2014 ◽

Vol 307 (9) ◽

pp. H1288-H1297 ◽

Cited By ~ 13

Author(s):

Jayson R. Gifford ◽

Stephen J. Ives ◽

Song-Young Park ◽

Robert H. I. Andtbacka ◽

John R. Hyngstrom ◽

...

Keyword(s):

Skeletal Muscle ◽

Ion Channels ◽

Human Skeletal Muscle ◽

Transient Receptor Potential ◽

Receptor Potential ◽

Ruthenium Red ◽

Temperature Sensitive ◽

Feed Arteries ◽

Skeletal Muscle Feed Arteries

The purpose of this study was to determine if heat inhibits α2-adrenergic vasocontraction, similarly to α1-adrenergic contraction, in isolated human skeletal muscle feed arteries (SMFA) and elucidate the role of the temperature-sensitive vanilloid-type transient receptor potential (TRPV) ion channels in this response. Isolated SMFA from 37 subjects were studied using wire myography. α1 [Phenylephrine (PE)]- and α2 [dexmedetomidine (DEX)]-contractions were induced at 37 and 39°C with and without TRPV family and TRPV4-specific inhibition [ruthenium red (RR) and RN-1734, respectively]. Endothelial function [acetylcholine (ACh)] and smooth muscle function [sodium nitroprusside (SNP) and potassium chloride (KCl)] were also assessed under these conditions. Heat and TRPV inhibition was further examined in endothelium-denuded arteries. Contraction data are reported as a percentage of maximal contraction elicited by 100 mM KCl (LTmax). DEX elicited a small and variable contractile response, one-fifth the magnitude of PE, which was not as clearly attenuated when heated from 37 to 39°C (12 ± 4 to 6 ± 2% LTmax; P = 0.18) as were PE-induced contractions (59 ± 5 to 24 ± 4% LTmax; P < 0.05). Both forms of TRPV inhibition restored PE-induced contraction at 39°C (P < 0.05) implicating these channels, particularly the TRPV4 channels, in the heat-induced attenuation of α1-adrenergic vasocontraction. TRPV inhibition significantly blunted ACh relaxation while denudation prevented heat-induced sympatholysis without having an additive effect when combined with TRPV inhibition. In conclusion, physiological increases in temperature elicit a sympatholysis-like inhibition of α1-adrenergic vasocontraction in human SMFA that appears to be mediated by endothelial TRPV4 ion channels.

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