A Skeletal Muscle-Mediated Anticontractile Response on Vascular Tone: Unraveling the Lactate-AMPK-NOS1 Pathway in Femoral Arteries.

Autor:	Fontes MT; Cardiovascular Translational Research Center, Department of Cell Biology and Anatomy, University of South Carolina, Columbia (SC) 29209, USA., Costa TJ; Cardiovascular Translational Research Center, Department of Cell Biology and Anatomy, University of South Carolina, Columbia (SC) 29209, USA.; Department of Pharmacology, Institute of Biomedical Science, University Of Sao Paulo, Sao Paulo (SP) 05508, Brazil., de Paula RB; Cardiovascular Translational Research Center, Department of Cell Biology and Anatomy, University of South Carolina, Columbia (SC) 29209, USA., Araújo FA; Cardiovascular Translational Research Center, Department of Cell Biology and Anatomy, University of South Carolina, Columbia (SC) 29209, USA., Barros PR; Cardiovascular Translational Research Center, Department of Cell Biology and Anatomy, University of South Carolina, Columbia (SC) 29209, USA., Townsend P; Cardiovascular Translational Research Center, Department of Cell Biology and Anatomy, University of South Carolina, Columbia (SC) 29209, USA., Butler L; Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater (OK) 74078, USA., Velazquez KT; Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia (SC) 29209, USA.; Columbia Department of Veterans Affairs Health Care System, Columbia (SC) 29209, USA., Hollis F; Columbia Department of Veterans Affairs Health Care System, Columbia (SC) 29209, USA.; Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia (SC) 29209, USA., Bomfim GF; Cardiovascular Translational Research Center, Department of Cell Biology and Anatomy, University of South Carolina, Columbia (SC) 29209, USA.; Health Research and Education Center, Federal University of Mato Grosso, Sinop (MT) 78556, Brazil., Butcher JT; Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater (OK) 74078, USA., McCarthy CG; Cardiovascular Translational Research Center, Department of Cell Biology and Anatomy, University of South Carolina, Columbia (SC) 29209, USA.; Biomedical Engineering Program, University of South Carolina, Columbia (SC) 29208, USA., Wenceslau CF; Cardiovascular Translational Research Center, Department of Cell Biology and Anatomy, University of South Carolina, Columbia (SC) 29209, USA.; Biomedical Engineering Program, University of South Carolina, Columbia (SC) 29208, USA.
Jazyk:	angličtina
Zdroj:	Function (Oxford, England) [Function (Oxf)] 2024 Nov 20; Vol. 5 (6).
DOI:	10.1093/function/zqae042
Abstrakt:	The regulation of vascular tone by perivascular tissues is a complex interplay of various paracrine factors. Here, we investigate the anti-contractile effect of skeletal muscle surrounding the femoral and carotid arteries and its underlying mechanisms. Using male and female Wistar rats, we demonstrated that serotonin, phenylephrine, and U-46619 induced a concentration-dependent vasoconstrictor response in femoral artery rings. Interestingly, this response was diminished in the presence of surrounding femoral skeletal muscle, irrespective of sex. No anti-contractile effect was observed when the carotid artery was exposed to its surrounding skeletal muscle. The observed effect in the femoral artery persisted even in the absence of endothelium and when the muscle was detached from the artery. Furthermore, the skeletal muscle surrounding the femoral artery was able to promote an anti-contractile effect in three other vascular beds (basilar, mesenteric, and carotid arteries). Using inhibitors of lactate dehydrogenase and the 1/4 monocarboxylate transporter, we confirmed the involvement of lactate, as both inhibitors were able to abolish the anti-contractile effect. However, lactate did not directly promote vasodilation; rather, it exerted its effect by activating 5' AMP-activated protein kinase (AMPK) and neuronal nitric oxide synthase (NOS1) in the skeletal muscle. Accordingly, Nω-propyl l-arginine, a specific inhibitor of NOS1, prevented the anti-contractile effect, as well as lactate-induced phosphorylation of NOS1 at the stimulatory serine site (1417) in primary skeletal muscle cells. Phosphorylation of NOS1 was reduced in the presence of Bay-3827, a selective AMPK inhibitor. In conclusion, femoral artery-associated skeletal muscle is a potent paracrine and endocrine organ that influences vascular tone in both sexes. Mechanistically, the anti-contractile effect involves muscle fiber type and/or its anatomical location but not the type of artery or its related vascular endothelium. Finally, the femoral artery anti-contractile effect is mediated by the lactate-AMPK-phospho-NOS1Ser1417-NO signaling axis. (© The Author(s) 2024. Published by Oxford University Press on behalf of American Physiological Society.)
Databáze:	MEDLINE
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