Forebrain Control Of Cardiovascular Function: Integrative And Cellular Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$834,233.00
Summary
Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. Measurements in humans have shown that the activity of sympathetic nerves is increased in a number of cardiovascular diseases, including heart failure and in many cases of high blood pressure. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart which can cause damage to the heart. It is not known what ....Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. Measurements in humans have shown that the activity of sympathetic nerves is increased in a number of cardiovascular diseases, including heart failure and in many cases of high blood pressure. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart which can cause damage to the heart. It is not known what causes this increased sympathetic activity, but one possibility is that it is due to the action of a circulating hormone called angiotensin, which acts on the brain, activating central nerve pathways which ultimately increase sympathetic activity. In this project we aim to test this hypothesis and thus help to unravel the mechanisms involved in the long term control of sympathetic activity and blood pressure.Read moreRead less
Novel Aspects Of Angiotensin AT1 Receptor Signalling Pathways
Funder
National Health and Medical Research Council
Funding Amount
$219,750.00
Summary
Hormones are chemicals released into the blood to influence tissue function by binding to specific sites (receptors) located on the cells found in a particular tissue. In general, it has been considered that a specific receptor activates a specific response when bound by the hormone. However, it is now clear that closely related hormones can activate different patterns of response even when they bind the one type of receptor. The full consequence of this phenomenon is still unknown. Its signific ....Hormones are chemicals released into the blood to influence tissue function by binding to specific sites (receptors) located on the cells found in a particular tissue. In general, it has been considered that a specific receptor activates a specific response when bound by the hormone. However, it is now clear that closely related hormones can activate different patterns of response even when they bind the one type of receptor. The full consequence of this phenomenon is still unknown. Its significance will be investigated in this project for important hormones which are involved in blood pressure control. The renin-angiotensin system makes the hormone angiotensin II which increases blood pressure through actions the heart, blood vessels, nerves and kidneys. One particular receptor type, the AT1 receptor, is responsible for the majority of effects of angiotensin II on these tissues and drugs that inhibit the activity of this receptor are very useful therapies for diseases such as hypertension and heart failure. However, Angiotensin III is a second hormone of the renin-angiotensin system that may also have important effects on tissue function when it activates the AT1 receptor. We have evidence that the type of tissue response that results from angiotensin III activated AT1 receptors is different from the response that results from angiotensin II activation of the same receptors. This raises the possibility that the effects of the AT1 receptor in cardiovascular disease might be differentially promoted by the two angiotensins. This project will investigate the mechanisms by which angiotensin II and anagiotensin III can elicit different activation via the AT1 receptor, and will determine the consequences of this differntial activation to tissue function.Read moreRead less