VENTRICULAR RECEPTOR CONTROL OF THE CIRCULATION

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.