Assessment of Vascular Reactivity Changes in Insulin Resistance and their Role in Blood Pressure Elevation

Curwen, Jon Owen (1997). Assessment of Vascular Reactivity Changes in Insulin Resistance and their Role in Blood Pressure Elevation. MPhil thesis The Open University.



The aim of this thesis was to investigate the link between changes in vascular reactivity and blood pressure in genetic and induced animal models of insulin resistance. Initially, the suitability of a pithed preparation to study vascular reactivity was established.

Attempts were made to alter the insulin sensitivity and hence the vascular reactivity of a group of AP Wistar rats by placing the animals on a high fat diet. The diet failed to alter the vascular reactivity of the animals tested. Further studies in different rat strains using different diets would be needed to properly investigate the effects of an induced insulin resistant state.

It was found that the insulin resistant obese AP Zucker rat had an increased vascular reactivity compared to the lean, insulin sensitive, AP Zucker rat. It was also found that the obese rat was hypertensive compared to the lean rat, although the difference in blood pressure was slight.

Pioglitazone, an insulin sensitising agent, decreased both blood pressure and vascular reactivity in the obese Zucker rat. However, despite having mild hypotensive effects, pioglitazone had no effect on the vascular reactivity of either the lean AP Zucker rat, the AP Wistar rat or the AP Spontaneously Hypertensive rat.

Two other insulin sensitising agents, vanadyl sulphate and ZD2079 (a β3-adrenoceptor agonist) failed to alter the vascular reactivity of either lean or obese AP Zucker rats. This confounded the results obtained when using the other insulin sensitising agent pioglitazone.

Overall, these results indicate a strong association between insulin resistance, vascular reactivity and increased blood pressure but a direct cause and effect relationship has been difficult to demonstrate.

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