TRPV1 channels in human skeletal muscle feed arteries: implications for vascular function

Abstract

To examine the role of transient receptor potential vanilloid type 1 (TRPV₁) ion channel in the vascular function of human skeletal muscle feed arteries (SMFAs) and if activation of this heat-sensitive receptor could be involved in modulating vascular function, SMFAs from 16 humans (63 ± 5, 41–89 yrs) were studied using wire myography with capsaicin (TRPV₁ agonist) and without (control). Specifically, phenylephrine (PE, α₁-adrenergic receptor agonist), dexemedetomidine (DEX, α₂-adrenergic receptor agonist), acetylcholine (ACh), and sodium nitroprusside (SNP) concentration response curves (CRCs) were performed to assess the role of TRPV1 channels in α-receptor-mediated vasocontraction as well as endothelium-dependent and independent vasorelaxation, respectively. Compared to control, capsaicin significantly attenuated maximum vasocontraction in response to PE (control: 52 ± 8; capsaicin: 21 ± 5%length-tension_max (LT_max)) and DEX (control: 29 ± 12; capsaicin: 2 ± 3%LT_max), while robustly enhancing maximum vasorelaxation with ACh (control: 78 ± 8; capsaicin: 108 ± 13%vasorelaxation), and less clearly enhancing the SNP response. Denudation of the endothelium greatly attenuated the maximum ACh-induced vasorelaxation equally in the control and capsaicin conditions (∼17%vasorelaxation), and abolished the attenuating effect of capsaicin on the maximal PE response (denuded+capsaicin: 61 ± 20%LT_max). Immunohistochemistry identified a relatively high density of TRPV₁ channels in the endothelium compared to the smooth muscle of the SMFAs, but, due to the far greater volume of smooth muscle, total TRPV₁ protein content was not significantly attenuated by denudation. Thus, SMFAs ubiquitously express functional TRPV₁ channels, which alter vascular function, in terms of α₁-receptors, in a predominantly endothelium dependent manner, conceivably contributing to the functional sympatholysis and unveiling a therapeutic target.

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