Chronic selective hypertriglyceridemia impairs endothelium-dependent vasodilatation in rats

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 hypemiglyceridemia (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 MT-rats exhibited a normal morphology. However, marked morphological differences were observed between vessels from 18-20 month old MT- and LT-rats. The endothelium-dependent vasodilator acetylcholine (2 to 50 mu g/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 MT-rats but was impaired in 12 and 18-20 month old MT-rats. In contrast the endothelium-independent vasodilator sodium nitroprusside enhanced blood how in both strains to a similar extent. Neither administration of the nitric oxide (NO) synthase (NOS) substrate, L-arginine, nor the NOS inhibitor N-G-nitro-L-arginine, affected the responsiveness to endothelium-dependent vasodilators in 12 month old MT-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 MT-rats. Determination of superoxide anion (O-2(-)) formation however, demonstrated a markedly elevated production of O-2(-) in aortae from MT-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 O-2(-) production and a subsequent decrease in bioavailable NO. (C) 1999 Elsevier Science B.V. All rights reserved.