title: Endothelium-dependent hyperpolarization-related relaxations diminish with age in murine saphenous arteries of both sexes.
abstract: OBJECTIVE
  We investigated the effects of aging on the contributions of NO and endothelium-dependent hyperpolarization (EDH) to endothelium-dependent relaxation in saphenous arteries of male and female C57BL/6J mice aged 12, 34 and 64 weeks.
  
  
  METHODS
  Vasomotor responses of saphenous arteries were analysed by wire myography in the absence and presence of stimuli of the endothelium, inhibitors of NOS, and inhibitors and stimulants of small (KCa 2.3) and intermediate (KCa 3.1) conductance calcium-activated potassium channels.
  
  
  RESULTS
  Arterial relaxing responses to sodium nitroprusside and to ACh in the absence of pharmacological inhibitors (indomethacin and L-NAME), were similar in all age groups and sexes, but those mediated by endothelium-derived NO were slightly but significantly increased in 64-week-old male mice. In the presence of inhibitors, 12-week-old animals showed pronounced ACh-induced relaxation, which was significantly reduced in 34- and 64-week-old mice of both sexes. The EDH-related component of ACh-induced relaxations was abolished by TRAM-34 (KCa 3.1 blocker) or UCL 1684 (KCa 2.3 blocker). Although the maximal relaxation induced by NS309 (KCa activator) was not affected by aging, the sensitivity for NS309 significantly decreased with aging. The presence of SKA-31 (KCa modulator) potentiated relaxations induced by ACh in arteries of 12-week-old but not older mice.
  
  
  CONCLUSIONS
  In a small muscular artery of mice of either sex, total endothelium-dependent relaxation is not affected by age. However, possibly due to changes in KCa channel function, the contribution of EDH to endothelium-dependent relaxations decreased with age. The contribution of endothelium-derived NO increases in old male mice.
authors.affiliation: Department of Anatomy and Embryology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Chennupati
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Lamers
authors.forename: S Eleonore
authors.initials: SE
authors.lastname: Koehler
authors.forename: Jo G R
authors.initials: JG
authors.lastname: De Mey
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging; D000473:Alkanes / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011806:Quinolinium Compounds / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C110349:6,10-diaza-3(1,3),8(1,4)dibenzena-1,5(1,4)diquinolinacyclodecaphane; D000473:Alkanes; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011720:Pyrazoles; D011806:Quinolinium Compounds; C411671:TRAM 34; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine
keywords: EDH-related responses; KCa2.3; KCa3.1; L-NAME