Native and oxidized low-density lipoproteins have different inhibitory effects on endothelium-derived relaxing factor in the rabbit aorta.
1. The effect of native low-density lipoproteins (LDL) and oxidized LDL (OXLDL) on the relaxations to endothelium-derived relaxing factor (EDRF) in isolated, intact aortic rings of the rabbit were investigated. 2. Native LDL induced a concentration-dependent reversible inhibition of the relaxations elicited by acetylcholine (ACh) or A23187, in rings pre-contracted by noradrenaline (NA), adrenaline (Ad) and 5-hydroxytryptamine (5-HT), but not phenylephrine (PE), which was not influenced by indomethacin. 3. The inhibition was surmountable in the rings pre-contracted with NA and Ad and only partially in those pre-contracted with 5-HT. 4. OXLDL induced an inhibition of the relaxations elicited by ACh and A23187 which was independent of the contractile agonist. The extent of inhibition and its reversibility varied with the LDL from individual donors, but was unaffected by indomethacin. 5. Native and oxidized LDL inhibited relaxations evoked by exogenous nitric oxide (NO) to the same extent. Higher concentrations of NO overcame the inhibition. The inhibition was independent of the contractile agonist and the preparation of LDL from individual donors. 6. Only OXLDL inhibited reversibly relaxations evoked by glyceryl trinitrate (GTN) and the inhibition was independent of the LDL preparation from individual donors. 7. This study demonstrates that native and OXLDL influence the response to EDRF in isolated aorta. We suggest that these lipoproteins may contribute to the attenuation of responses to EDRF found in isolated arteries from hypercholesterolaemic and atherosclerotic animals.
Jacobs
M
M
Department of Pharmacology, Royal Free Hospital School of Medicine, London.
Plane
F
F
Bruckdorfer
K R
KR
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D010084:Oxidation-Reduction; D011817:Rabbits
D008077:Lipoproteins, LDL; D009569:Nitric Oxide; D000001:Calcimycin; D005996:Nitroglycerin; D000109:Acetylcholine