The research proposed in this application is concerned with the reflex control of the cardiovascular system. Specifically, we wish to investigate the role played by receptors in the left ventricle whose axons traverse the vagi. These experiments will be conducted in conscious, instrumented dogs whenever possible. Several important areas of reflex control will be addressed in this research. We will define the mechanical stimuli that are necessary for evoking a bradycardia and a reduction in peripheral sympathetic nerve activity by using acute aortic stenosis. We will determine the interaction of ventricular receptor mediated reflexes with arterial baroreceptor mediated reflexes in the control of total and regional vascular resistance by using the techniques of reversable isolation of the carotid sinuses and intracoronary infusion of veratrine and catecholamines. The latter substance will help to define the role of alterations in myocardial contractility on left ventricular receptor stimulation. The effect of left ventricular receptor stimulation on coronary blood flow will also be investigated in conscious dogs. In this experiment as in those cited above the efferent components of these reflexes will be investigated using appropriate autonomic blockade. Another important segment of this research proposal is concerned with the role of cardiac prostaglandins in the initiation of potentiation of the left ventricular receptor mediated reflexes on cardiac dynamics and peripheral vascular resistance. Based on previous work it is likely that prostacylin (PGI2) can stimulate endings in the left ventricle and evoke a Bezold-Jarisch reflex. We will investigate the effects of prostaglandins on the cardiac reflex control of a variety of hemodynamic parameters. Finally, many of the experiments cited above will be repeated in dogs with chronic volume overload heart failure. Cardiac receptor reflex control of the circulation may be altered in many disease states (such as heart failure) and cardiac prostaglandin production may be increased. Studying heart failure dogs will help to uncover the mechanisms for altered reflex function in this disease state and should contribute to our overall understanding of the neural control of the circulation in health and disease.
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