Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kusterer, K; Pohl, T; Fortmeyer, HP; März, W; Scharnagl, H; Oldenburg, A; Angermüller, S; Fleming, I; Usadel, KH; Busse, R.
Chronic selective hypertriglyceridemia impairs endothelium-dependent vasodilatation in rats.
CARDIOVASC RES 1999 42: 783-793.
Doi: 10.1016/S0008-6363(98)00331-9
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- Co-Autor*innen der Med Uni Graz
- März Winfried
- Scharnagl Hubert
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- Abstract:
- OBJECTIVE/METHODS: 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. CONCLUSION: 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetylcholine - pharmacology
- Animals - pharmacology
- Aorta - metabolism
- Arginine - pharmacology
- Blotting, Western - pharmacology
- Carotid Arteries - metabolism
- Chronic Disease - metabolism
- Endothelium, Vascular - metabolism
- Hindlimb - blood supply
- Hypertriglyceridemia - metabolism
- Male - metabolism
- Nitric Oxide - metabolism
- Nitric Oxide Synthase - analysis
- Nitroarginine - pharmacology
- Nitroprusside - pharmacology
- Rats - pharmacology
- Rats, Sprague-Dawley - pharmacology
- Regional Blood Flow - drug effects
- Research Support, Non-U.S. Gov't - drug effects
- Superoxides - analysis
- Vasodilation - drug effects
- Find related publications in this database (Keywords)
- endothelium
- superoxide anion
- nitric oxide
- rat