title: Nitric oxide synthase and cyclooxygenase modulate β-adrenergic cutaneous vasodilatation and sweating in young men.
abstract: β-Adrenergic receptor agonists such as isoproterenol induce cutaneous vasodilatation and sweating in humans, but the mechanisms underpinning this response remain unresolved. Using intradermal microdialysis, we evaluated the roles of nitric oxide synthase (NOS) and cyclooxygenase (COX) in β-adrenergic cutaneous vasodilatation and sweating elicited by administration of isoproterenol. We show that while NOS contributes to β-adrenergic cutaneous vasodilatation, COX restricts cutaneous vasodilatation. We also show that combined inhibition of NOS and COX augments β-adrenergic sweating These new findings advance our basic knowledge regarding the physiological control of cutaneous blood flow and sweating, and provide important and new information to better understand the physiological significance of β-adrenergic receptors in the skin.
  
  
  
  β-Adrenergic receptor agonists such as isoproterenol can induce cutaneous vasodilatation and sweating in humans, but the mechanisms underpinning this response remain unresolved. We evaluated the hypotheses that (1) nitric oxide synthase (NOS) contributes to β-adrenergic cutaneous vasodilatation, whereas cyclooxygenase (COX) limits the vasodilatation, and (2) COX contributes to β-adrenergic sweating. In 10 young males (25 ± 5 years), cutaneous vascular conductance (CVC) and sweat rate were evaluated at four intradermal forearm skin sites infused with (1) lactated Ringer solution (control), (2) 10 mm Nω-nitro-l-arginine (l-NNA), a non-specific NOS inhibitor, (3) 10 mm ketorolac, a non-specific COX inhibitor, or (4) a combination of l-NNA and ketorolac. All sites were co-administered with a high dose of isoproterenol (100 μm) for 3 min to maximally induce β-adrenergic sweating (β-adrenergic sweating is significantly blunted by subsequent activations). Approximately 60 min after the washout period, three incremental doses of isoproterenol were co-administered (1, 10 and 100 μm each for 25 min). Increases in CVC induced by the first and second 100 μm isoproterenol were attenuated by l-NNA alone, and those in response to all doses of isoproterenol were reduced by l-NNA with co-infusion of ketorolac (all P ≤ 0.05). Ketorolac alone augmented increases in CVC induced by 10 μm and by the second 100 μm isoproterenol (both P ≤ 0.05). While isoproterenol-induced sweating was not affected by the separate administration of l-NNA or ketorolac (all P > 0.05), their combined administration augmented sweating elicited by the first 3 min of 100 μm isoproterenol (P = 0.05). We show that while NOS contributes to β-adrenergic cutaneous vasodilatation, COX restrains the vasodilatation. Finally, combined inhibition of NOS and COX augments β-adrenergic sweating.
authors: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada.
authors: Naoto
authors: N
authors: Fujii
authors: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada.
authors: Brendan D
authors: BD
authors: McNeely
authors: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Canada.
authors: Glen P
authors: 0000-0001-8683-6973
authors: GP
authors: Kenny
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D002196:Capillaries / Q000378:metabolism / Q000502:physiology; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D020910:Ketorolac / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine / Q000008:administration & dosage / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012867:Skin / Q000098:blood supply*; D013546:Sweating; D014664:Vasodilation
chemical_list: D000318:Adrenergic beta-Agonists; D016861:Cyclooxygenase Inhibitors; D011943:Receptors, Adrenergic, beta; D019335:Nitroarginine; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases; D007545:Isoproterenol; D020910:Ketorolac
keywords: adenylyl cyclase; adrenaline; adrenergic receptors; cAMP; thermoregulation; β-adrenoceptor