Abstract/Summary

There is extensive evidence demonstrating the protective effects of fish oils or omega-3 polyunsaturated fatty acids (n-3 PUFAs) against cardiovascular diseases. It is widely accepted that the main n-3 PUFAs involved with these therapeutic effects are DHA and EPA. These PUFAs have been reported to reduce blood pressure by improving various vasodilation pathways. However, most of these studies focus on either DHA or EPA in a single artery. Therefore, this PhD project involved the comprehensive characterisation of the underlying vasodilation mechanisms of both n-3 PUFAs using conduit and resistance rat arteries. Wire myograph was used to examine acute vasodilation effects of n-3 PUFAs in preconstricted rat arteries, mostly via the use of pharmacological inhibitors. Stable cells that allowed inducible expression of TRPV4 was generated to assess changes in channel activity with n-3 PUFAs, using Fluo-4 AM based calcium imaging. n-3 PUFA mediated activation of KATP channels was also examined by using stable cells and whole cell patch clamp. The novel role of IKCa was observed in DHA-induced relaxation. Consistent with previous studies, BKCa was also involved in the relaxation effects of n-3 PUFAs. The presence of KATP and Kv7 component in n-3 PUFA-mediated vasodilation was also demonstrated for the first time. One of the most important highlights of my findings is the heterogeneity in the vasodilation mechanisms that was dependent upon both the type of n-3 PUFA and artery. These findings will be invaluable for future vascular studies that focus on investigating the prospect of using n-3 PUFA and novel fatty acid analogues as treatments that target specific vasodilation pathways, that are involved in providing therapeutic benefits against certain cardiovascular disorders.