Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.674442
Title: Resistance vessel structure and function in an experimental and genetic model of insulin-dependent diabetes mellitus
Author: Heygate, Katherine M.
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 1996
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Abstract:
Microvascular disease is a major complication of diabetes but little is known about how diabetes effects the precapillary resistance arteries. The work described in this thesis was designed to investigate the effects of insulin-dependent diabetes on the structure and function of the resistance vasculature, using an experimental and genetic animal model of diabetes. Preliminary in vitro studies of normal resistance arteries showed that hyperglycaemia (40mM glucose) resulted in impaired endothelium-dependent relaxation to the vasodilator acetylcholine (ACh). This effect was shown to not be due to an increase in osmolarity. Resistance arteries from the spontaneously diabetic BioBred rat at the onset of diabetes, and after long-term insulin treatment showed a significant increase in the media wall: lumen ratio, cross sectional area and media thickness compared to their age-matched non-diabetic controls. Significant impairment to both ACh and bradykinin (BK) was evident in the diabetic vessels, which was unaffected by pretreatment with L-arginine, or free radical scavengers. Inhibition of EDRF revealed a significant leftward shift in the dose response curve to noradrenaline (NA) in the recent onset diabetic vessels, but not in the insulin treated. However, the shift was not as marked as that seen in the age-matched control vessels which suggests a reduction of basal EDRF release in the diabetic vessels. Incubation with a cyclo-oxygenase inhibitor indomethacin significantly improved ACh relaxation in the diabetic vessels indicating the abnormality arises from an over-production of a vasoconstricting prostanoid. Resistance arteries from chemically-induced diabetic rats after 6 or 12 weeks of diabetes were examined, along with the response to the intra-portal transplantation of islets. Inhibition of EDRF revealed an increased response to NA in the diabetic vessels; whereas, vascular reactivity to NA in the islet transplanted and control groups remained unaltered. Endothelium-dependent relaxation to ACh and BK was not impaired in the diabetic vessels. Indeed, the ACh relaxation was significantly augmented in the untreated 6 week diabetic group indicating an increased release of EDRF early in chemical-induced diabetes, but this disappeared with a long duration of diabetes. These studies highlight differences in the response of the resistance artery structure and function to genetic or chemical-induced diabetes mellitus.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.674442  DOI: Not available
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