We work closely with Professor Julian Paton to investigate the roles of angiotensin II, nitric oxide and the neurotransmitter GABA, in the central control mechanisms responsible for maintaining blood pressure at normal levels.
It is vital that blood pressure is tightly regulated in order to supply all major organs with blood. `Essential hypertension' describes the condition where blood pressure is higher than normal over a prolonged period of time. This can lead to atherosclerosis, retinopathy, kidney disease, myocardial infarction and stroke.
Angiotensin II is a peptide that acts on blood vessel walls to modify arterial pressure. Blocking its action brings about a reduction in blood pressure; angiotensin II antagonists are standard drugs in the treatment of hypertension.
We have found that angiotensin II not only affects vessel walls, but also plays an important role in the brainstem. One part of the brainstem, the Nucleus of the Solitary Tract (NTS), exerts control over blood pressure via the `arterial baroreceptor reflex', a feedback loop that returns levels to normal if arterial pressure increases. Angiotensin II leads to inhibition of this reflex. It stimulates the release of nitric oxide, which in turn increases release of inhibitory transmitter GABA, GABA then inhibits the reflex and prevents lowering of blood pressure.
We use a variety of techniques, including viral gene transfer, high-resolution confocal imaging and electrophysiology. By using an experimental design that combines molecular, cellular, imaging, whole system and electrophysiological methods, we are able to draw reliable conclusions about the physiology of blood pressure regulation. This is only possible by applying an integrative and interdisciplinary approach.
Through understanding the details of these mechanisms and how they may be reversed, possibilities will be opened for developing more effective treatment of essential hypertension.
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