Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study we compared the vascular reactivity and integrity of the nitric oxide (NO)-cyclic 3',5'-guanosine monophopsphate (cGMP) pathway in carotid arteries of hyper- and normolipidemic rabbits. Vasodilation to acetylcholine, nitroglycerin, and sodium nitroprusside was desensitized in hyperlipidemia, but the nitroprusside-induced relaxation was normalized by an NO synthase inhibitor in endothelium-intact and -denuded vessels. Hyperlipidemic carotid arteries exhibited increased basal NO (detected by EPR spin-trapping) and reactive oxygen species formation (detected by chemiluminescence), whereas acetylcholine-induced NO formation was nearly abolished. Hyperlipidemia increased NADPH-dependent superoxide formation in carotid membranes, and carotid cryosections stained with the fluorescent dye dihydroethidium revealed increased endothelial and medial reactive oxygen species formation. Hyperlipidemia elicited macrophage invasion into the carotid wall, as detected by a dot-immunoblot. The basal activity of cGMP-dependent proteinkinase, the nitroprusside-stimulated activity of soluble guanylyl cyclase, and its protein expression were decreased by hyperlipidemia. The cGMP phosphodiesterase activity was marginally increased by hyperlipidemia, such that the ratio of cGMP-forming vs. -degrading capacity was decreased by 2-fold. Hyperlipidemia triggers infiltration of macrophages into the carotid wall and endothelial as well as smooth muscle superoxide formation. Consequently, relaxation of the carotid arteries are impaired due to smooth muscle and endothelial dysfunction.
Nitric Oxide 2006 Nov
PMID:Mechanisms underlying dysfunction of carotid arteries in genetically hyperlipidemic rabbits. 1659 5

Nitric oxide (NO) exerts a plethora of vascular beneficial effects. The NO-releasing beta-blocker nebivolol is a racemic mixture of D/L-enantiomers that displays negative inotropic as well as direct vasodilating activity. The in vivo antiatherogenic activity of therapeutic doses of the beta-blocker with antioxidant properties carvedilol (12.5mg/day) or nebivolol (5mg/day) was tested in cholesterol-fed rabbits. Animals received a 1% cholesterol-rich diet alone (controls) or mixed with drugs (treated animals) for 8 weeks. While it did not affect hyperlipidemia, nebivolol inhibited the development of atherosclerosis, expressed as computer-assisted imaging analysis of aortic area covered by lesions (23.3+/-4.1% in treated vs 38.2+/-6.4% in control animals, p<0.01). Differently, in our experimental condition of therapeutic drug doses, this antiatherogenic effect did not reach statistical significance in rabbits treated with carvedilol (32.5+/-5.1% aortic area covered by lesions, p=NS vs controls). Plasma nitrates increased in rabbits treated with nebivolol while both beta-blockers reduced LDL oxidation. Moreover, nebivolol induced a consistent increase of endothelial reactivity and aortic eNOS expression compared with control animals (p<0.05) and those receiving carvedilol (p<0.05). Since NO may exert beneficial effects in atherosclerosis, a NO-dependent mechanism could explain this data. These observations suggest that the NO-releasing beta-blocker, nebivolol, might represent an effective pharmacological approach for preventing atherosclerotic lesion progression.
Nitric Oxide 2008 Aug
PMID:Therapeutic dose of nebivolol, a nitric oxide-releasing beta-blocker, reduces atherosclerosis in cholesterol-fed rabbits. 1843 36

The endothelium consists of a monolayer of Endothelial Cells (ECs) which form the inner cellular lining of veins, arteries, capillaries and lymphatic vessels. ECs interact with the blood and lymph. The endothelium fulfils functions such as vasodilatation, regulation of adhesion, infiltration of leukocytes, inhibition of platelet adhesion, vessel remodeling and lipoprotein metabolism. ECs synthesize and release compounds such as Nitric Oxide (NO), metabolites of arachidonic acid, Reactive Oxygen Species (ROS) and enzymes that degrade the extracellular matrix. Endothelial dysfunction represents a phenotype prone to atherogenesis and may be used as a marker of atherosclerotic risk. Such dysfunction includes impaired synthesis and availability of NO and an imbalance in the relative contribution of endothelialderived relaxing factors and contracting factors such as endothelin-1 and angiotensin. This dysfunction appears before the earliest anatomic evidence of atherosclerosis and could be an important initial step in further development of atherosclerosis. Endothelial dysfunction was historically treated with vitamin C supplementation and L-arginine supplementation. Short term improvement of the expression of adhesion molecule and endothelial function during antioxidant therapy has been observed. Statins are used in the treatment of hyperlipidaemia, a risk factor for cardiovascular disease. Future studies should focus on identifying the mechanisms involved in the beneficial effects of statins on the endothelium. This may help develop drugs specifically aimed at endothelial dysfunction.
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PMID:Endothelial Dysfunction in Dyslipidaemia: Molecular Mechanisms and Clinical Implications. 3148 Sep 95