Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.592619
Title: Vascular and nervous dysfunction in streptozotocin-diabetic rats : development and treatment
Author: Jack, Alison
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1999
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Abstract:
The effect of experimental diabetes on mesenteric vascular function and nerve conduction velocity (NCV) was studied in adult male rats. Perfusion of the mesenteric bed with phenylephrine to evoke constriction and acetylcholine (Ach), to evoke relaxation was carried out. Increases in perfusion pressure in response to phenylephrine were significantly impaired in diabetic animals. Sensitivity and the maximum relaxation response to Ach were also significantly impaired following pre-contraction with phenylephrine in diabetic animals although sensitivity was not impaired in the presence of NG-nitro-L-arginine (NOLA) indicating dysfunction of the nitric oxide (NO) component of endothelium dependent relaxation. As vasodilation to the NO donor Na+ nitroprusside (SNP) was not altered by diabetes this impairment in the NO system must lie proximal to the diffusion of NO to the smooth muscle. Upon removal of NO the maximum relaxation response to Ach was almost completely abolished following two months of untreated diabetes, which suggests that endothelium dependent hyperpolarising factor (EDHF) activity is minimal at this stage. Pre-contraction of the vasculature with KC1 instead of phenylephrine inhibits EDHF function and when combined with NOLA abolishes relaxation in both control and diabetic animals. Thus EDHF and NO are the only relaxing factors released by the endothelium in response to Ach. Impaired vasodilatory and vasoconstrictive responses were observed following electrical stimulation of mesenteric perivascular nerves in diabetic tissue. The former deficit is proposed to be the result of impaired release of the vasodilatory peptide Calcitonin Gene Related Peptide (CGRP) from nerve terminals. As the addition of NOLA to the perfusate significantly increased the maximum relaxation response of both control and diabetic tissue, and perfusion with arginine abolished it, it is further proposed that NO exerts an inhibitory action on CGRP-mediated vasodilation. The impairment in vasoconstriction in response to electrical stimulation was significantly reduced following equilibration of the tissue with NOLA.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.592619  DOI: Not available
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