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Low density lipoproteins and haemodynamic changes in the isolated perfused rat kidney

Rahman, Md. Muhibur; (1999) Low density lipoproteins and haemodynamic changes in the isolated perfused rat kidney. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Low density lipoproteins (LDL) may be involved in the pathogenesis of glomerulosclerosis and progressive renal dysfunction associated with atherosclerotic renal artery stenosis. This study was undertaken to investigate the effects of native (N-LDL) and oxidised LDL (Ox-LDL) on renal vascular response and function in an isolated perfused rat kidney (IPRX) model. Ox-LDL, but not N-LDL, caused vasoconstriction in the IPRK, as evidenced by a significant dose-dependent reduction in renal perfusate flow (RPF). [¹⁴C] insulin clearance and fractional reabsorption of sodium were also reduced during Ox-LDL infusion whereas no significant change occurred with N-LDL. To elucidate the possible role of nitric oxide (NO), urinary cGMP, nitrate and nitrite excretion were measured during N-LDL and Ox-LDL infusion. There was a significant decrease in urinary excretion of cGMP during Ox-LDL infusion but nitrate and nitrite excretion remained unchanged. NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA) (10 μM) significantly increased Ox-LDL induced vasoconstriction but L-NMMA (500 μM) which suppressed NO synthesis almost completely, greatly attenuated the vasoconstriction. NO donor S-nitrosoglutathione (10 μM) significantly diminished the vasoconstrictory effect of Ox-LDL. Furthermore L-arginine supplementation significantly decreased Ox-LDL induced vasoconstriction. The role of reactive oxygen species was also studied by adding superoxide dismutase (SOD), catalase and mannitol. These free radical scavengers had a significant inhibitory effect and the combination of SOD and catalase almost completely abolished the vasoconstriction due to Ox-LDL. The influence of short term diet induced hyperlipidaemia was also investigated and the role of L-arginine supplementation in the drinking water and compensatory increase in renal function following uninephrectomy were evaluated. RPF, [¹⁴C] insulin clearance and basal cGMP excretion rate were significantly reduced in the rats on high fat diet compared to the control rats. Concomitant administration of L-arginine reversed the effect of high fat diet. Compensatory renal functional changes after a short duration (2 weeks) following uninephrectomy also abolished the effects of hyperlipidaemia. The results suggest that Ox-LDL induced vasoconstriction in IPRX may be mediated by decreased activity of NO due to inactivation of NO by reactive oxygen species. L-arginine and the free radical scavengers SOD, catalase and mannitol provided protection against Ox-LDL induced vasoconstriction in this model.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Low density lipoproteins and haemodynamic changes in the isolated perfused rat kidney
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Health and environmental sciences; Renal dysfunction
URI: https://discovery.ucl.ac.uk/id/eprint/10104774
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