title: Chronic selective hypertriglyceridemia impairs endothelium-dependent vasodilatation in rats.
abstract: OBJECTIVE
  In order to investigate whether selective hypertriglyceridemia impairs endothelium-dependent vasodilatation in the rat hindlimb, rats were selectively bred to establish two strains, one with a pronounced hypertriglyceridemia (HT) and the other with normal plasma levels of triglycerides (LT).
  
  
  RESULTS
  Carotid arteries and aortae removed from 3, 6, 9 and 12 month old LT- and HT-rats exhibited a normal morphology. However, marked morphological differences were observed between vessels from 18-20 month old HT- and LT-rats. The endothelium-dependent vasodilator acetylcholine (2 to 50 micrograms/kg), administered into the iliac artery, elicited a concentration-dependent increase in hindlimb blood flow which was not different in 3, 6 and 9 month old LT- or HT-rats but was impaired in 12 and 18-20 month old HT-rats. In contrast the endothelium-independent vasodilator sodium nitroprusside enhanced blood flow in both strains to a similar extent. Neither administration of the nitric oxide (NO) synthase (NOS) substrate, L-arginine, nor the NOS inhibitor NGnitro-L-arginine, affected the responsiveness to endothelium-dependent vasodilators in 12 month old HT-rats. These attenuated responses could not be attributed to a decrease in endothelial NOS expression as Western blot analysis revealed identical levels of this enzyme in the aortae and carotid arteries from LT- and HT-rats. Determination of superoxide anion (O2-) formation however, demonstrated a markedly elevated production of O2- in aortae from HT-rats.
  
  
  CONCLUSIONS
  We conclude that chronic selective hypertriglyceridemia, an independent risk factor in the development and progression of atherosclerosis, leads to an endothelial dysfunction which is associated with an increased vascular O2- production and a subsequent decrease in bioavailable NO.
authors.affiliation: Department of Internal Medicine I, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kusterer
authors.forename: T
authors.initials: T
authors.lastname: Pohl
authors.forename: H P
authors.initials: HP
authors.lastname: Fortmeyer
authors.forename: W
authors.initials: W
authors.lastname: März
authors.forename: H
authors.initials: H
authors.lastname: Scharnagl
authors.forename: A
authors.initials: A
authors.lastname: Oldenburg
authors.forename: S
authors.initials: S
authors.lastname: Angermüller
authors.forename: I
authors.initials: I
authors.lastname: Fleming
authors.forename: K H
authors.initials: KH
authors.lastname: Usadel
authors.forename: R
authors.initials: R
authors.lastname: Busse
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001120:Arginine / Q000494:pharmacology; D015153:Blotting, Western; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006614:Hindlimb / Q000098:blood supply; D015228:Hypertriglyceridemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013481:Superoxides / Q000032:analysis; D014664:Vasodilation / Q000187:drug effects
chemical_list: D013481:Superoxides; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine