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Clinical Science and Molecular Medicine (1976) 51, 353s-355s. Cardiac reflexes conducted by vagal afferents in normotensive and renal hypertensive dogs P. KEZDI Cox Heart Institute, Dayton, Ohio, U.S.A. baroreflexes in the tonic regulation of the blood pressure and their possible participation in the altered blood pressure regulation of hypertension. summary 1. The renal sympathetic reflex responses to transient balloon occlusion of the descending aorta (systemic baroreceptor activation) and the ascending aorta (cardiac stretch-receptor activation) have been studied together with blood pressure increases after successive cutting of carotid sinus, aortic and vagus nerves in acute experiments in the dog. 2. Results from these experiments provide evidence for cardiac vagal afferent participation in the tonic regulation of systemic blood pressure. 3. In other experiments the reflex pressureresponse curve of the isolated gracilis muscle at constant flow to transient ascending aorta occlusion was measured. This curve was moved to the right in renal hypertensive dogs as compared with normotensive dogs. The threshold response of left ventricular vagal afferent nerves was shifted to higher left ventricular pressure in the former. 3. These findings indicate resetting of ventricular receptors in hypertensive animals. Methods Key words : blood pressure, hypertension, vagal afferents, ventricular receptors. Introduction Reflexes originating in the heart have been traced to the atria, the ventricles and the coronary arteries (Shepherd, 1973; Linden, 1975). Afferent pathways are mostly in the vagus nerves and impulses are conducted by myelinated and non-myelinated fibres. The clinical role of the ventricular receptors is little known. We have been interested in the role of cardiac Correspondence: Dr Paul Kezdi, Cox Heart Institute, 3525 Southern Boulevard, Dayton, Ohio, U.S.A. Experiments were performed in mongrel dogs of both sexes. Three groups were studied. Group 1 was composed of eight normotensive dogs in which reflex changes of sympathetic nerve activity were recorded in response to temporary occlusion of the descending and ascending aorta before and after successive cutting of the systemic baroreceptors. The renal nerve was isolated by retroperitoneal approach to isolate the kidney. In group 2 (eight normotensive dogs) and group 3 (six renal hypertensive dogs) reflex changes in perfusion pressure of the isolated constant-flow gracilis muscle were recorded in response to graded temporary occlusion of the ascending aorta. Hypertension was produced by cellophan wrapping of one kidney and contralateral nephrectomy. Temporary occlusion of the aorta was produced by a balloon catheter, which was introduced through a left carotid artery. The tip of this catheter was advanced into the left ventricle to measure left ventricular pressure while the balloon was in the ascending portion of the aorta, about 1 cm above the aortic valve. A graded increase of left ventricular pressure could be produced by inflating the balloon to different degrees. Occlusion of the descending aorta in group 1 dogs was carried out by a similar catheter introduced through the femoral artery to the mid-portion of the thoracic aorta. The gracilis muscle artery was perfused by a roller pump with arterial blood from the opposite femoral artery. A flow probe was placed on the gracilis muscle artery and the flow was adjusted 353s 354s P. Kezdi so that the perfusion pressure approximated to base-line systemic pressure. Pressure was measured by Statham P53D strain gauges through a catheter from a side branch of the artery. At the completion of the gracilis perfusion pressure recordings, the left vagus was isolated and fibres were separated to record afferent nerve activity from the left ventricle in response to graded occlusion of the ascending aorta (group 2 and group 3 only). For nerve activity multifibre and single-fibre recordings were made with platinum-iridium bipolar electrodes, Tektronic 122 low level preamplifier, Astrodata amplifiers and Honeywell 1507 Visicorder. At the termination of the experiment the chest was opened and the location of the receptors from which recordings were made was identified after stopping the heart by an overdose of intravenous sodium pentobarbitone (Nembutal). Localized pressure was applied to the wall of the left ventricle at different points with a cotton-covered haernostat. The dogs were anaesthetized with chloraloseurethane, respired by a Harvard animal respirator and paralysed by succinylcholine to prevent muscle artifacts. The carotid sinus and aortic nerves were isolated in the neck in each experiment and identified electroneurographically for later selective cutting. The aortic nerve was isolated at the junction of the vagus with the superior laryngeal nerve. Care was taken not to damage the rest of the vagus nerve. Results arily occluded, however, raising the left ventricular pressure even higher (with systemic pressure dropping to 30 mmHg) there was marked sympathetic inhibition irrespective of whether or not the systemic baroreceptor nerves were intact or cut. Cutting the vagus nerves further increased base-line sympathetic activity and eliminated the reflex inhibition by occlusion of the ascending aorta. Reflex response of gracilis muscle perfusion pressure The mean arterial pressure in norrnotensive dogs was 90 mmHg and in hypertensive dogs was 135 mmHg. -.OI -50 Mean LV pressure (mmHg) Reflex inhibition of renal sympathetic nerve activity FIG.1. Perfusion pressure response for the gracilis muscle artery to gradual increase of left ventricular (LV) mean In group 1 dogs renal sympathetic nerve,activity was first recorded with all systemic baroreceptors intact. Temporary occlusion of the descending aorta was then carried out to raise the pressure in the entire aortic arch. This resulted in reflex inhibition of sympathetic activity. After release of the occlusion and re-establishing base-line sympathetic activity, blood pressure and heart rate, cutting of both carotid sinus nerves increased baseline sympathetic activity and decreased the reflex inhibition of sympathetic activity by temporary occlusion of the descending aorta. Subsequently when the aortic nerves were cut, renal sympathetic activity further increased and reflex inhibition to temporary occlusion of the descending aorta was not present. When the ascending aorta was tempor- pressure in normotensive ( 0 ) and hypertensive (M) dogs. In normotensive (group 2) dogs the gracilis muscle perfusion pressure showed the first decrease to temporary graded balloon occlusion of the ascending aorta when the mean left ventricular pressure was increased from 47 to 73 mmHg average (threshold response). With a more marked increase of the left ventricular pressure further decrease of the gracilis muscle perfusion pressure occurred. Maximum pressure decrease was reached when left ventricular mean pressure was raised to 150 mmHg (see Fig. 1). Graded increase of left ventricular pressure in hypertensive dogs showed the first response of the gracilis perfusion pressure at 102 mmHg mean left Cardiac reflexes in normo- and hyper-tension ventricular pressure, compared with 73 mmHg in the normotensive dogs. A maximum response was reached at 174 mmHg. The gracilis muscle perfusion pressure-response curve was shifted to the right in response to left ventricular pressure increase in the hypertensive dogs when compared with the normotensive dogs (see Fig. 1). Vagal afferent nerve activity Vagal afferent nerve activity from ventricular receptors showed sparse pulse synchronous discharges at base-line pressures, both in normotensive and hypertensive dogs. When gradual balloon occlusion of the ascending aorta was carried out, pressure in the left ventricle increased and pressure in the aorta beyond the occlusion rapidly decreased. Afferent vagal nerve activity increased, first by pulse synchronous discharge and then by continuous activity as the pressure was further increased in the left ventricle. In hypertensive animals, the threshold pressure at which new receptors were recruited was at a higher left ventricular pressure. Atrial nerve activity was also increased slightly during balloon occlusion but never became continuous. Discussion The experiments with group 1 dogs confirm that cardiopulmonary vagal afferent fibres play a role in the tonic regulation ofthe circulation as indicated by the additional increase of post-ganglionic sympathetic nerve discharge after cutting of the vagus nerves, after the carotid sinus and aortic nerves have previously been cut. Cardiopulmonary vagal afferent pathways exert a powerful reflex inhibition of sympathetic discharge, decrease of 355s heart rate and blood pressure. Receptors of this reflex are located predominantly in the left ventricle. Left atrial distension (volume increase) was shown by Mason & Ledsome (1974) to affect predominantly renal vascular resistance but not resistance in the isolated perfused hind limb. The threshold of the ventricular receptors is significantly higher than the threshold of systemic baroreceptors, the aortic nerve receptors having a higher threshold than the carotid sinus receptors. VentricJar receptors are activated probably only when ventricular pressure is raised to a considerably high value. However, pressures which stimulate ventricular receptor activity can be present in hypertension. It appears that the threshold and the range of the reflex activity of the ventricular receptors shift to the right in chronic renal hypertensive dogs. This would be analogous to the changes which occur in the threshold of systemic baroreceptors. This is probably due to the decreased compliance of the left ventricle in hypertension and is part of the general autonomic nervous system resetting which takes place. Acknowledgment Supported by grant HL 15004 of the National Institute of Health. References LINDEN,R.J. (1975) Reflexes from the heart. Progress in Cardiovascular Disease, 18, 201-221. MASON,J.M. & LEDSOME, J.R. (1974) Effects of obstruction of the mitral orifice or distension of the pulmonary veinatrial junctions on renal and hind-limb vascular resistance in the dog. Circulation Research, 35, 24-32. SHEPHERD, J.T. (1973) lntrathoracic baroreflexes. Mayo Clinic Proceedings, 48,42643 7.