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The effects of lysophospholipids and oxidised low-density lipoproteins on the L-arginine: Nitric oxide pathways in isolated rabbit and rat aorta

Kerr, Paul Martin; (1993) The effects of lysophospholipids and oxidised low-density lipoproteins on the L-arginine: Nitric oxide pathways in isolated rabbit and rat aorta. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Elevated plasma levels of low-density lipoproteins (LDL) are a major risk factor for the development of atherosclerosis. Atherosclerotic vessels from humans and animals show impaired endothelium-dependent relaxations (EDR) and altered responses to contractile agonists. Recent evidence suggests that oxidation of LDL is a key process in atherogenesis and plays an important role in the alterations in vascular reactivity. This study investigated the effects of a major component of oxidised LDL (OXLDL), lysophosphatidylcholine (LPC), on vascular responses in isolated rabbit and rat aortic rings. In addition, the effects of OXLDL on EDR in rat aortic rings was also examined. Furthermore, the possibility that impaired EDR in atherosclerotic vessels could be restored by L-arginine was investigated. LPC caused immediate, dose dependent and partially reversible inhibition of EDR evoked by ACh, ATP and A23187 in rabbit aortic rings. This inhibition was decreased by serum albumin but not by L-arginine or indomethacin. Relaxations to exogenous NO and glyceryl trinitrate in endothelium-denuded tissues were unaffected by LPC, but responses were inhibited in endothelium-intact rings suggesting the release of an inhibitory factor from the endothelium. LPC also evokes EDR which are mediated by the release of NO. This dual effect of LPC can be demonstrated in the same tissue. Contractile responses to phenylephrine (PE) and 5-HT were unaffected in denuded tissues, but were inhibited in endothelium-intact tissues, again suggesting the release of a factor from the endothelium. Relaxations evoked by L-arginine in isolated rat aortic rings were mediated by an inducible nitric oxide synthase (NOS). At a concentration that inhibited relaxations elicited by ACh, OXLDL did not influence L-arginine-evoked relaxations, whereas LPC potentiated responses. NOS activity induced in vivo by endotoxin injection, was studied ex vivo by observation of PE-evoked contractions. Contractions were attenuated in rings from endotoxin-treated rats. However, the effect of this treatment was unaffected by the presence of OXLDL or LPC. Aortic rings from WHHL rabbits which spontaneously develop atherosclerosis, showed impaired EDR. This impairment was not influenced by incubation of the tissues with L-arginine. Furthermore, rabbits fed a diet supplemented with L-arginine did not show improved endothelium- dependent responses in vitro. In addition, L-arginine feeding did not influence contractile responses to PE. In conclusion, LPC can modulate EDR and contractile responses in isolated tissues although, these effects do not mimic those reported for OXLDL. In contrast, OXLDL and LPC do not inhibit the activity of an inducible form of NOS. Finally, the impairment of EDR observed in atherosclerotic vessels cannot be reversed by the administration of L-arginine.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The effects of lysophospholipids and oxidised low-density lipoproteins on the L-arginine: Nitric oxide pathways in isolated rabbit and rat aorta
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10102307
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