title: The involvement of norepinephrine, neuropeptide Y, and nitric oxide in the cutaneous vasodilator response to local heating in humans.
abstract: Presynaptic blockade of cutaneous vasoconstrictor nerves (VCN) abolishes the axon reflex (AR) during slow local heating (SLH) and reduces the vasodilator response. In a two-part study, forearm sites were instrumented with microdialysis fibers, local heaters, and laser-Doppler flow probes. Sites were locally heated from 33 to 40 degrees C over 70 min. In part 1, we tested whether this effect of VCN acted via nitric oxide synthase (NOS). In five subjects, treatments were as follows: 1) untreated; 2) bretylium, preventing neurotransmitter release; 3) N(G)-nitro-L-arginine methyl ester (L-NAME) to inhibit NOS; and 4) combined bretylium + L-NAME. At treated sites, the AR was absent, and there was an attenuation of the ultimate vasodilation (P < 0.05), which was not different among those sites (P > 0.05). In part 2, we tested whether norepinephrine and/or neuropeptide Y is involved in the cutaneous vasodilator response to SLH. In seven subjects, treatments were as follows: 1) untreated; 2) propranolol and yohimbine to antagonize alpha- and beta-receptors; 3) BIBP-3226 to antagonize Y(1) receptors; and 4) combined propranolol + yohimbine + BIBP-3226. Treatment with propranolol + yohimbine or BIBP-3226 significantly increased the temperature at which AR occurred (n = 4) or abolished it (n = 3). The combination treatment consistently eliminated it. Importantly, ultimate vasodilation with SLH at the treated sites was significantly (P < 0.05) less than at the control. These data suggest that norepinephrine and neuropeptide Y are important in the initiation of the AR and for achieving a complete vasodilator response. Since VCN and NOS blockade in combination do not have an inhibition greater than either alone, these data suggest that VCN promote heat-induced vasodilation via a nitric oxide-dependent mechanism.
authors.affiliation: Department of Physiology, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Hodges
authors.forename: Wojciech A
authors.initials: WA
authors.lastname: Kosiba
authors.forename: Kun
authors.initials: K
authors.lastname: Zhao
authors.forename: John M
authors.initials: JM
authors.lastname: Johnson
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001369:Axons / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008297:Male; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors; D017661:Receptors, Presynaptic / Q000187:drug effects; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D018674:Adrenergic Antagonists; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; C092926:BIBP 3226; D004791:Enzyme Inhibitors; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D017661:Receptors, Presynaptic; D015016:Yohimbine; D009569:Nitric Oxide; D001120:Arginine; D011433:Propranolol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine