title: Prostacyclin does not affect sweating but induces skin vasodilatation to a greater extent in older versus younger women: roles of NO and KCachannels.
abstract: What is the central question of this study? It remains unknown whether ageing modulates prostacyclin-induced cutaneous vasodilatation in women. What is the main finding and its importance? Prostacyclin induced cutaneous vasodilatation, albeit the magnitude of increase at lower concentrations of prostacyclin was greater in older relative to young women. This response was associated with greater contributions of nitric oxide synthase and calcium-activated potassium channels. Our results suggest that administration of prostacyclin might be an effective therapy to reverse microvascular hypoperfusion, especially in older women. We previously reported that prostacyclin induces cutaneous vasodilatation but not sweating in younger and older men. Furthermore, we demonstrated that nitric oxide synthase and calcium-activated potassium (KCa) channels contribute to the prostacyclin-induced cutaneous vasodilatation in younger men, although these contributions are diminished in older men. Given that the effects of ageing might differ between men and women, the above results cannot simply be applied to women. In this study, cutaneous vascular conductance and sweat rate were evaluated in younger (mean ± SD, 22 ± 3 years old) and older (55 ± 7 years old) women (10 per group) at four intradermal forearm skin sites treated as follows: (i) lactated Ringer solution without any drug (control); (ii) 10 mm NG-nitro-l-arginine (l-NNA), a non-specific nitric oxide synthase inhibitor; (iii) 50 mm tetraethylammonium (TEA), a non-specific KCachannel blocker; or (iv) 10 mm l-NNA plus 50 mm TEA. All four sites were co-administered with prostacyclin in an incremental manner (0.04, 0.4, 4, 40 and 400 μm, each for 25 min). Surprisingly, increases in cutaneous vascular conductance in response to 0.04-4 μm prostacyclin were greater in older relative to younger women (all P ≤ 0.05), and these age-related differences were diminished when both l-NNA and TEA were administered simultaneously (all P > 0.05). No effect on sweat rate was observed in either group (all concentrations, P > 0.05). We show that although prostacyclin does not mediate sweating, it induces cutaneous vasodilatation, and this response elicited by lower concentrations of prostacyclin is greater in older relative to younger women. This greater cutaneous vasodilatation in older women is likely to be attributable to nitric oxide synthase- and KCachannel-dependent mechanisms.
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Ontario, Canada.|Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba City, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Fujii
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Brendan D
authors.initials: BD
authors.lastname: McNeely
authors.affiliation: Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba City, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishiyasu
authors.affiliation: Human and Environmental Physiology Research Unit, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Glen P
authors.identifier: 0000-0001-8683-6973
authors.initials: GP
authors.lastname: Kenny
mesh_terms: D000328:Adult; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019335:Nitroarginine / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D013546:Sweating / Q000187:drug effects*; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D024681:Potassium Channels, Calcium-Activated; D019335:Nitroarginine; D009569:Nitric Oxide; D019789:Tetraethylammonium; D011464:Epoprostenol; D019001:Nitric Oxide Synthase
keywords: IP receptor; ageing; cAMP; female; heat loss; microcirculation; prostanoids; skin blood flow