title: Differential effect of cerivastatin and L-arginine on the vascular function of human radial and left internal thoracic arteries.
abstract: BACKGROUND
  There are a number of strategies to restore/preserve endothelial function. We have compared the effects of Cerivastatin (CS) to those of L-arginine (L-ARG) supplementation on the endothelial function of human arterial grafts.
  
  
  METHODS
  During coronary artery bypass grafting, specimens of radial artery (RA) and left internal thoracic artery (LITA) were obtained. Specimens were divided into vascular rings, which were incubated with either 10(-6) mol/L CS, 10(-3) mol/L L-ARG, or vehicle (control) for 2 or 24 hours. Endothelial function was examined with acethylcholine (10(-9) to 10(-5) mol/L) following contraction by 3 x 10(-8) mol/L endothelin-1.
  
  
  RESULTS
  Although no significant differences were observed in the RA at 2 hours, after 24 hours incubation, endothelium-dependent vasodilatation was significantly higher in CS group (68.4 +/- 5.0%; n = 6) compared to L-ARG group (49.9 +/- 5.4%; n = 7, p < 0.05) and control group (33.8 +/- 2.9%; n = 13, p < 0.0001). In addition, there was a significant increase in L-ARG group compared to control (p < 0.01). After 2 hours incubation of the LITA, CS failed to enhance endothelium-dependent vasodilatation compared to control (44.1 +/- 4.9%; n = 9, vs. 40.0 +/- 5.2%; n = 16, respectively, NS), while L-ARG increased it (64.7 +/- 4.9%; n = 7, p < 0.05 vs. CS and p < 0.01 vs. control). However, this increase disappeared at 24 hours although there was a higher trend of endothelium-dependent vasodilatation in CS group (30.3 +/- 3.7%; n = 8 in L-ARG, 56.5 +/- 8.8%; n = 9 in CS and 41.0 +/- 5.5%; n = 18 in control).
  
  
  CONCLUSIONS
  CS preserved endothelium-dependent vasodilatation of RA greater than L-ARG. These findings suggest that the use of statins may be an effective therapeutic strategy to preserve endothelial function in the RA grafts, and could have important implications in the clinical practice.
authors.affiliation: National Heart and Lung Institute, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, United Kingdom.
authors.forename: Koki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Sharif
authors.initials: S
authors.lastname: Al-Ruzzeh
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Chester
authors.forename: Charles
authors.initials: C
authors.lastname: Ilsley
authors.forename: Magdi H
authors.initials: MH
authors.lastname: Yacoub
authors.forename: Mohamed
authors.initials: M
authors.lastname: Amrani
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D004730:Endothelium, Vascular / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology*; D017534:Radial Artery / Q000187:drug effects*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; D014665:Vasodilator Agents; D001120:Arginine; C086276:cerivastatin; D000109:Acetylcholine