The influence of chronic ventricular distension and hypertrophy (secondary to increased afterloads) on cardiac, peripheral vascular, and neural responses mediated by receptors located in the left ventricle is not known. It is the aim of this research to evaluate in the conscious dog the reflex control of the circulation during chemical and mechanical stimulation of ventricular receptors in: a) normal, time-control dogs, b) renal hypertensive dogs (RH: one-kidney, one-clip), and c) dogs with chronic ascending aortic occlusion (AAO). Depending upon the experiment to be carried out, chronic instrumentation will be established to obtain measurements of: 1) arterial pressure (AP- mmHg), 2) heart rate (HR-bpm), 3) left ventricular pressures (mmHg), 4) renal and iliac blood flows (KHz; ml/min), 5) left ventricular diameters (mm), and 6) integrated lumbar sympathetic nerve activity (LSNA-Hz). Stimulus-response curves relating AP, HR, and iliac vascular resistance to varied doses of intracoronary veratridine (.05-.8 ug/kg) will be constructed at one week intervals for six weeks in time-control dogs and in the experimental groups (RH and chronic AAO). Acute AAO will also be performed to analyze the HR response to mechanical stimulation of ventricular receptors observing the same time frame as above in each group of dogs. Experiments will be conducted to evaluate the influence of chemical and mechanical stimulation of ventricular receptors on the arterial baroreflex control of HR and LSNA. At one week intervals for six weeks, full AP-HR baroreflex curves will be constructed during a) continuous intracoronary veratrine infusions (.4-.8 ug/kg/min) and b) acute AAO. At the end of the six weeks, silver-silver chloride electrodes will be positioned around a lumbar sympathetic nerve branch (L2-L4) to construct full AP-LSNA baroreflex curves before and during chemical or mechanical stimulation of ventricular receptors in the conscious dog (time-control, RH and chronic AAO). Terminal, acute experiments involving electroneurographic recordings will be constructed to evaluate the discharge characteristics of left ventricular C-fibers in response to chemical and mechanical stimulation in each group of dogs. The significance of the proposed research is that it will provide new and important information of the role of ventricular receptors in circulatory and neural reflex control in normal, conscious dogs and dogs with chronic ventricular distension secondary to systemic hypertension or aortic stenosis.
