title: Evaluation of the effects of urotensin II and soluble epoxide hydrolase inhibitor on skin microvessel tone in healthy controls and heart failure patients.
abstract: BACKGROUND
  Urotensin II (UII) is a potent vasoactive peptide that exerts differential effects on heart failure (HF) patients compared to health controls. However, the mechanism of action remains unclear. The role of soluble epoxide hydrolase (sEH) as a mediator of UII in the vasculature has not been explored.
  
  
  OBJECTIVE
  The aim of this study was to examine the effect of UII in the presence and absence of sEH inhibitor AUDA on skin microvessel tone in HF patients and healthy controls using iontophoresis and laser Doppler velocimetry. UII (10(-7) M) and AUDA (10(-10), 10(-7), and 10(-5) M) were administered to the forearm of participants by iontophoresis for 30 seconds. Laser Doppler velocimetry was performed for 5 minutes to measure flux through the subcutaneous blood vessels. Response (flux) was measured for 5 minutes per concentration with 25 continuous scans.
  
  
  RESULTS
  UII increased flux in healthy controls by 39% (P < 0.05) and increased flux in HF patients by 6% (ns). AUDA (10(-10) and 10(-7) M) administration further decreased flux by 115% (P < 0.05) and 255% (P < 0.0001), respectively in healthy controls. In HF patients, AUDA (10(-10), 10(-7), and 10(-5) M) further increased flux by 77% (P < 0.05), 67% (P < 0.01), and 100% (P < 0.05), respectively. AUDA alone at 10(-7) M increased flux in both groups by 31% (healthy controls, P < 0.05) and 36% (HF, P < 0.01).
  
  
  CONCLUSIONS
  Taken together, the presence of HF appeared to abrogate the vasodilator responsiveness of sEH inhibitor. These results suggest an important role for both UII and sEH in vascular regulation and that sEH may be involved in mediating UII effects. Furthermore, the study highlights the therapeutic potential of sEH inhibitors for the treatment of HF.
authors: Centre of Cardiovascular Research and Education in Therapeutics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
authors: Lavinia
authors: L
authors: Tran
authors: Andrew R
authors: AR
authors: Kompa
authors: Bing H
authors: BH
authors: Wang
authors: Henry
authors: H
authors: Krum
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000368:Aged; D002196:Capillaries / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D007850:Lauric Acids / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D018401:Sample Size; D012867:Skin / Q000098:blood supply*; D014579:Urotensins / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: C504897:12-(3-adamantan-1-ylureido)dodecanoic acid; D004791:Enzyme Inhibitors; D007850:Lauric Acids; D014579:Urotensins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; C029677:urotensin II; D004851:Epoxide Hydrolases; D000109:Acetylcholine; D000218:Adamantane; D009638:Norepinephrine