Premium
Cutaneous Blood Flow during Intradermal Exogenous Nitric Oxide Administration in Young and Older Adults: Roles for Cyclooxygenase and Calcium‐Activated Potassium Channels?
Author(s) -
Fujii Naoto,
Singh Maya Sarah,
Minson Christopher T,
Brunt Vienna E,
Boulay Pierre,
Sigal Ronald J,
Kenny Glen P
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.763.21
Subject(s) - sodium nitroprusside , ketorolac , medicine , nitric oxide , potassium channel , cyclooxygenase , vasodilation , anesthesia , pharmacology , endocrinology , chemistry , analgesic , biochemistry , enzyme
Nitric oxide (NO) increases cutaneous blood flow. We hypothesized that cutaneous blood flow during intradermal administration of sodium nitroprusside (SNP, a NO donor) is in part regulated by cyclooxygenase (COX) and calcium‐activated potassium (KCa) channels in young adults. We also hypothesized that these contributions are diminished in older adults as ageing can reduce COX‐derived vasodilator prostanoids and downregulate KCa channels. In 10 young (3 males and 7 females, 23 ± 5 years) and 10 older (3 males and 7 females, 54 ± 4 years) adults, cutaneous vascular conductance (CVC) was measured at four intradermal forearm skin sites receiving 1) Ringers (Control), 2) 50 m M tetraethylammonium (TEA), a non‐specific KCa channel blocker, 3) 10 m M ketorolac, a non‐specific COX inhibitor, or 4) 50 m M TEA + 10 m M ketorolac. All skin sites were co‐infused with incremental doses of SNP (0.005, 0.05, 0.5, 5, 50 m M each for 25 min). Compared to the Control site, CVC during SNP administration was similar at the ketorolac site (0.005–50m M , all P > 0.05) but was lower at the TEA and TEA + ketorolac sites (0.005–5m M , all P < 0.05) in young adults. In older adults, ketorolac increased CVC relative to the Control site during SNP administration (0.005–0.5m M , all P < 0.05), but this increase disappeared when TEA was co‐administered (all P > 0.05). TEA alone did not modulate CVC during SNP administration in older adults (0.005–50m M , all P > 0.05). We show that during intradermal exogenous NO administration, KCa channels, but not COX, contribute to cutaneous blood flow regulation in young adults, while COX reduces cutaneous blood flow by attenuating KCa channel‐dependent cutaneous vasodilation in older adults. Support or Funding Information This study was supported by the Natural Sciences and Engineering Research Council of Canada (Discover grant, RGPIN‐06313‐2014; Discovery Grants Program ‐ Accelerator Supplement, RGPAS‐462252‐2014), and by Canada Foundation for Innovation (Leaders Opportunity Fund, 22529) (funds held by Dr. Glen P. Kenny).