title: Cutaneous active vasodilation in humans is mediated by cholinergic nerve cotransmission.
abstract: During heat stress, increases in blood flow in nonglabrous skin in humans are mediated through active vasodilation by an unknown neurotransmitter mechanism. To investigate this mechanism, a three-part study was performed to determine the following: (1) Is muscarinic receptor activation necessary for active cutaneous vasodilation? We iontophoretically applied atropine to a small area of forearm skin. At that site and an untreated control site, we measured the vasomotor (laser-Doppler blood flow [LDF]) and sudomotor (relative humidity) responses to whole-body heat stress. Blood pressure was monitored. Cutaneous vascular conductance (CVC) was calculated (LDF divided by mean arterial pressure). Sweating was blocked at treated sites only. CVC rose at both sites (P < .05 at each site); thus, cutaneous active vasodilation is not effected through muscarinic receptors. (2) Are nonmuscarinic cholinergic receptors present on cutaneous arterioles? Acetylcholine (ACh) was iontophoretically applied to forearm skin at sites pretreated by atropine iontophoresis and at untreated sites. ACh increased CVC at untreated sites (P < .05) but not at atropinized sites. Thus, the only functional cholinergic receptors on cutaneous vessels are muscarinic. (3) Does cutaneous active vasodilation involve cholinergic nerve cotransmission? Botulinum toxin was injected intradermally in the forearm to block release of ACh and any coreleased neurotransmitters. Heat stress was performed as in part 1 of the study. At treated sites, CVC and relative humidity remained at baseline levels during heat stress (P > .05). Active vasodilator and sudomotor responses to heat stress were abolished by botulinum toxin. We conclude that cholinergic nerve activation mediates cutaneous active vasodilation through release of an unknown cotransmitter, not through ACh.
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio 78284, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Kellogg
authors.forename: P E
authors.initials: PE
authors.lastname: Pérgola
authors.forename: K L
authors.initials: KL
authors.lastname: Piest
authors.forename: W A
authors.initials: WA
authors.lastname: Kosiba
authors.forename: C G
authors.initials: CG
authors.lastname: Crandall
authors.forename: M
authors.initials: M
authors.lastname: Grossmann
authors.forename: J M
authors.initials: JM
authors.lastname: Johnson
mesh_terms: D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D001285:Atropine / Q000494:pharmacology; D001905:Botulinum Toxins / Q000494:pharmacology; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006813:Humidity; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D011950:Receptors, Cholinergic / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects; D013312:Stress, Physiological / Q000503:physiopathology; D009435:Synaptic Transmission; D014664:Vasodilation
chemical_list: D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D001285:Atropine; D001905:Botulinum Toxins; D000109:Acetylcholine