Neurotransmitters In Synaptic Inputs To Medullary Neurons Subserving The Baroreflex
Funder
National Health and Medical Research Council
Funding Amount
$470,500.00
Summary
The baroreflex rapidly adjusts arterial blood pressure to meet changing physiological needs. The reflex alters vascular resistance and changes the rate, volume and force at which blood is expelled from the heart, ensuring that organs are adequately supplied with blood-borne nutrients and oxygen. Changes in baroreflex function occur during exercise, correlate with increased mortality and morbidity from heart failure and myocardial infarction and are responsible for postural hypotension in the eld ....The baroreflex rapidly adjusts arterial blood pressure to meet changing physiological needs. The reflex alters vascular resistance and changes the rate, volume and force at which blood is expelled from the heart, ensuring that organs are adequately supplied with blood-borne nutrients and oxygen. Changes in baroreflex function occur during exercise, correlate with increased mortality and morbidity from heart failure and myocardial infarction and are responsible for postural hypotension in the elderly. Three areas in the brainstem are critical for transmission of the arterial baroreflex. However, it is still not known exactly which chemicals (neurotransmitters) are used to convey baroreflex information to and between neurons in these key sites. In this project, we will use state-of-the-art anatomical techniques to examine nerve pathways that subserve the arterial baroreflex. By changing blood pressure and specifically tagging nerve cells that respond, we can focus on neurons activated by baroreflex stimuli. Concentrating on neurotransmitters known to affect blood pressure control in the medulla, we will then label one or more of these in nerve fibers surrounding the barosensitive neurons. Finally, we will determine by light and electron microscopy the relationships between the labelled nerve fibers and the barosensitive neurons. These relationships will show which neurotransmitters could influence barosensitive neurons directly, which indirectly and which not at all. This project will increase our understanding of the baroreflex by clarifying which neurochemicals convey baroreflex information amongst the key groups of brainstem neurons. These data will form the foundation for new studies on changes in nerve pathways that underlie baroreflex dysfunction in such conditions as postural hypotension. Identifying transmitters for the baroreflex may also point to, or rule out, new drug treatments for disturbances in baroreflex function.Read moreRead less
Neurocircuitry Of A Novel Gastrointestinal-circulatory Reflex
Funder
National Health and Medical Research Council
Funding Amount
$515,625.00
Summary
The gastrointestinal tract receives about one third of the blood pumped around the body by the heart. This implies that the gut circulation plays a major role in blood pressure control. Gut blood flow changes according to the demands imposed by altered behavioural activity. Engagement in physical exercise results in increased blood flow to the working muscles of the limbs and diversion away from the gut. Alternatively, food consumption promotes an increase in blood flow to the gut to aid digesti ....The gastrointestinal tract receives about one third of the blood pumped around the body by the heart. This implies that the gut circulation plays a major role in blood pressure control. Gut blood flow changes according to the demands imposed by altered behavioural activity. Engagement in physical exercise results in increased blood flow to the working muscles of the limbs and diversion away from the gut. Alternatively, food consumption promotes an increase in blood flow to the gut to aid digestion. While this is a normal bodily process, there are also adverse implications of the re-distribution of blood flow: in the elderly compensation for these changes is often impaired and can result in low blood pressure and fainting. In addition, the incidence of angina-related heart pain is greater after food consumption and this may be associated with re-distribution of blood flow to the gut. Cholecystokinin (CCK), a hormone which is released from special cells that line the intestine, plays a role in the control of blood flow to the gut. We have developed the hypothesis that CCK acts on nerves which send a signal to the brain which, in turn, acting through other nerves, produces an increase in the flow of blood to the gut. This project is designed to study the nerve pathways in the brain which control this novel mechanism. We will record the activity of specific brain cells and nerves which are involved in the control of the blood supply to the gut. We will also examine which chemicals the brain cells and nerves use for communication with each other and so build up a model of the brain areas which are involved in gut blood flow control. This project will shed new light on the mechanisms of gut blood flow control and identify the associated brain pathways. The information will be of importance in the treatment of diseases of the circulation and food consumption-related cardiovascular changes in the elderly and obese as well as in sufferers of angina.Read moreRead less
The Quinoline Antimalarials: Mechanisms Of Action And Resistance In Plasmodium Falciparum
Funder
National Health and Medical Research Council
Funding Amount
$316,650.00
Summary
Malaria is a debilitating parasitic disease that is responsible for the deaths of about two million children each year. As drugs, such as chloroquine, become increasingly useless due to the development of parasite resistance, there is an urgent need to understand the mode of action of these antimalarials so that replacement drugs can be designed. We propose to test the hypothesis that chloroquine acts by interfering with the detoxification of the by-products that are produced when the parasite f ....Malaria is a debilitating parasitic disease that is responsible for the deaths of about two million children each year. As drugs, such as chloroquine, become increasingly useless due to the development of parasite resistance, there is an urgent need to understand the mode of action of these antimalarials so that replacement drugs can be designed. We propose to test the hypothesis that chloroquine acts by interfering with the detoxification of the by-products that are produced when the parasite feeds on haemoglobin. We propose that the parasite develops resistance to chloroquine by excluding either the drug or the toxic by-products from the site of action. We further propose that proteins of the digestive vacuole of the parasite are involved in the development of resistance to chloroquine. We plan to identify and characterise these proteins and to use this information to design novel antimalarial drugs.Read moreRead less