Control of catecholamine synthesis and secretion by angiotensin II.

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In the stress response the catecholamines, including adrenaline, are secreted by the adrenal gland and the brain. This leads to the synthesis of new catecholamines in order to replace those that were lost. Synthesis of catecholamines is controlled by the activity and the amount of the enzyme tyrosine hydroxylase. Catecholamine synthesis and secretion is therefore a fundamental physiological process. This can be controlled by a number of mechanisms, including hormones such as angiotensin II. Angiotensin II has a number of functions including the control of blood pressure and body fluid homeostasis. Angiotensin II acts on the adrenal glands, the sympathetic nerves and the brain to produce these effects. It does so by increasing the secretion of catecholamines and these in turn modulate blood pressure and fluid homeostasis. The mechanism(s) whereby angiotensin II induces catecholamine secretion is not known, nor is it known how this leads to increased tyrosine hydroxylase activity and synthesis. The aim of this grant is therefore to determine how angiotensin II induces the activation of tyrosine hydroxylase, the secretion of catecholamines and the synthesis of new tyrosine hydroxylase. The significance of this work is that it will allow us to better understand how angiotensin II works and it will provide insights into the generation and control of hypertension and the mechanisms of the stress response. It is known that the pathways involved in angiotensin II stimulation of catecholamine secretion can be blocked by inhibitors of protein kinases and this leads to a reduction in blood pressure. It is therefore likely that this work will have therapeutic implications.