Transient receptor potential vanilloid type 1 channels contribute to reflex cutaneous vasodilation in humans

Abstract

Wong BJ, Fieger SM. Transient receptor potential vanilloid type 1 channels contribute to reflex cutaneous vasodilation in humans. J Appl Physiol 112: 2037-2042, 2012. First published April 19, 2012 doi:10.1152/japplphysiol.00209.2012.-Mechanisms underlying the cutaneous vasodilation in response to an increase in core temperature remain unresolved. The purpose of this study was to determine a potential contribution of transient receptor potential vanilloid type 1 (TRPV-1) channels to reflex cutaneous vasodilation. Twelve subjects were equipped with four microdialysis fibers on the ventral forearm, and each site randomly received 1) 90% propylene glycol ϩ 10% lactated Ringer (vehicle control); 2) 10 mM L-NAME; 3) 20 mM capsazepine to inhibit TRPV-1 channels; 4) combined 10 mM L-NAME ϩ 20 mM capsazepine. Whole body heating was achieved via water-perfused suits sufficient to raise oral temperature at least 0.8°C above baseline. Maximal skin blood flow was achieved by local heating to 43°C and infusion of 28 mM nitroprusside. Systemic arterial pressure (SAP) was measured, and skin blood flow was monitored via laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as LDF/SAP and normalized to maximal vasodilation (%CVC max). Capsazepine sites were significantly reduced compared with control (50 Ϯ 4%CVC max vs. 67 Ϯ 5%CVC max, respectively; P Ͻ 0.05). L-NAME (33 Ϯ 3%CVCmax) and L-NAME ϩ capsazepine (30 Ϯ 4%CVCmax) sites were attenuated compared with control (P Ͻ 0.01) and capsazepine (P Ͻ 0.05); however, there was no difference between L-NAME and combined L-NAME ϩ capsazepine. These data suggest TRPV-1 channels participate in reflex cutaneous vasodilation and TRPV-1 channels may account for a portion of the NO component. TRPV-1 channels may have a direct neural contribution or have an indirect effect via increased arterial blood temperature. Whether the TRPV-1 channels directly or indirectly contribute to reflex cutaneous vasodilation remains uncertain. microdialysis; heat stress; nitric oxide INCREASES IN SKIN BLOOD FLOW and sweating represent humans' primary physiological defense against an increase in core temperature. The initial increase in skin blood flow during hyperthermia is driven primarily by withdrawal of tonic sympathetic vasoconstrictor tone, which results in approximate doubling of resting thermoneutral skin blood flow(8, 23). Further increases in skin blood flow, concomitant with the onset of sweating, are mediated by reflex sympathetic cholinergic nerve activity (8). This reflex cutaneous active vasodilation accounts for 85-95% of the increase in skin blood flow during hyperthermia and can result in nearly 8 liters/min of cardiac output directed to the cutaneous vasculature(24).The co-transmission theory of cutaneous active vasodilation suggests acetylcholine and one or more unknown vasodilators are co-released from sympathetic cholinergic nerves, where acetylcholine is primarily responsible for the sweat response and the unknown vasodilator(s) are responsible for the refle...

Transient Receptor Potential Vanilloid-1 Channels Contribute to the Regulation of Acid- and Base-Induced Vasomotor Responses

“…Similar vasomotor effects were also found with endogenous TRPV1 agonists, such as the arachidonic acid metabolites anandamide and 20-hydroxyeicosatetraenoic acid [42,43]. Besides the ligand agonists, the involvement of the TRPV1 channel has also been shown in the mediation of heat-induced vascular responses [20,21]. Here, we show for the first time that TRPV1 plays a limiting function in the relaxation and constriction induced by acidic and basic stimuli, respectively.…”

“…It is also known that through its intrinsic tonic activation, TRPV1 is involved in the maintenance of bodily homeostasis [19]. While the role of TRPV1 has been characterized in the vascular response to chemical agonists [17,18] and warmth [20,21], it remains unknown whether and how TRPV1 contributes to the mediation of acid-base-induced vascular responses in different vessel types.…”

To reheat, or to not reheat: that is the question: The efficacy of a local reheating protocol on mechanisms of cutaneous vasodilatation

“…As per our pilot work and previous studies, drugs were infused for a minimum of 60 min before collection of data. Sodium nitroprusside (SNP) was infused at all sites at a concentration of 58 mM for 35 min to elicit maximal cutaneous vascular conductance (CVC) at the end of protocols 2 and 3 (Carter and Hodges, 2011;Kellogg et al, 2009;Kellogg et al, 2010;Wong and Fieger, 2012).…”

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

“…Given their known temperature sensitivity (2,6,11,21,36) and interaction with vascular function ranging from coronary to cutaneous circulation (7,10,21,37,40), we hypothesized that the TRPV ion channels would serve as the link between elevated temperature and attenuated ␣-adrenergic contraction in isolated human SMFA. Indeed, as illustrated in Fig.…”

“…Additionally, it is important to note that the arteries in this preparation were studied in isolation, thus precluding a role of the central nervous system in the sympatholytic effect of heat. Nevertheless, it should be noted that even with careful dissection it is likely impossible to completely remove all nerve fibers from the SMFA and therefore there remains the possibility that TRPV ion channels on sensory and/or sympathetic nerve endings embedded in the artery wall mediate the vascular response in a manner similar to the axon reflex that mediates cutaneous hyperemia in response to local heating (12,37).…”