Role of baroreceptor afferents on area postrema-induced inhibition of sympathetic activity.

Activation of the area postrema by either electrical stimulation or chemical application of L-glutamate has been shown to result in an enhancement of cardiovascular baroreflexes similar to that seen with systemic infusions of arginine vasopressin (AVP). In addition, it has been found that the effects of AVP on baroreflex inhibition of renal sympathetic nerve activity (RSNA) are similar to those observed with phenylephrine following lesions of the area postrema or after partial denervation of baroreceptor afferents. The present study was undertaken to determine the role of baroreceptor afferent input on area postrema stimulation-induced decreases in sympathetic activity. In anesthetized rabbits, the responses of arterial pressure, heart rate, and RSNA to area postrema electrical stimulation were obtained before and after progressive sinoaortic denervation and vagotomy. Stimulation of the area postrema in carotid sinus-denervated animals consistently decreased RSNA in a frequency-dependent manner. However, following bilateral removal of both the aortic nerves and the vagi, electrical stimulation of the area postrema had no effect on RSNA. These results suggest that the ability of area postrema stimulation to inhibit RSNA is dependent on the presence of baroreceptor afferent input.

Neurohumoral interactions in conscious dehydrated rabbit.

The purpose of this study was to examine the role of angiotensin II (ANG II), arginine vasopressin (AVP), and neurogenic mechanisms in maintaining arterial pressure (MAP) in conscious water-deprived rabbits. Water deprivation produced marked increases in plasma renin activity and the concentration of AVP; however, plasma catecholamine concentrations were unchanged. Arterial baroreflex control of renal sympathetic nerve activity (RSNA) and heart rate (HR) was similar in water-replete and dehydrated animals. Administration of an ANG II receptor antagonist (ANG IIX) to water-deprived animals produced a small decrease in MAP but no significant changes in HR or mesenteric and hindquarters vascular resistances. Similarly, there was no significant effect on MAP, HR, or regional hemodynamics when dehydrated animals received an AVP-V1 antagonist (AVPX). RSNA increased by maximums of 61 and 43% in response to ANG IIX and AVPX, respectively. Combined administration of ANG IIX and AVPX produced significant decreases in MAP (-9 mmHg) and hindquarters resistance (-24%) and 117% and 23 beat/min increases in RSNA and HR, respectively. The effect on mesenteric resistance was variable; however, the response was generally a decrease. We conclude that ANG II and AVP pressor mechanisms are activated to sustain MAP in the dehydrated state. In contrast, the basal level and baroreflex control of sympathetic nervous system activity are unchanged from the water-replete state. However, activation of sympathetic nerve activity may become important in maintaining peripheral resistance when ANG II and AVP receptors are blocked in water-deprived animals.

Interaction of vasopressin with area postrema during volume expansion.

Effects of arginine vasopressin (AVP) on inhibition of renal sympathetic nerve activity (RSNA) during activation of cardiopulmonary reflexes by volume expansion were examined in conscious sinoaortic-denervated rabbits. The role of the area postrema in mediating these effects was also evaluated in rabbits subjected to area postrema lesion. Animals were subjected to 12% volume expansion with whole blood alone or during infusion of AVP (0.6 mU . kg-1 . min-1). Volume expansion in area postrema-intact animals caused a progressive reflex inhibition of RSNA (maximum = -36.5 +/- 3.3% delta RSNA). Vasopressin infusion did not significantly alter resting arterial pressure, right atrial pressure, heart rate, or RSNA. However, maximum inhibition of RSNA during volume expansion (-62.6 +/- 3.2% delta RSNA) was significantly augmented during AVP infusion, and the augmentation was reversed by a specific vascular (V1) AVP receptor antagonist. Vagotomy eliminated RSNA responses to volume expansion with or without AVP. In area postrema-lesioned animals, the RSNA response to volume expansion was similar to that of intact animals (-31.8 +/- 2.3% delta RSNA). However, AVP did not augment the RSNA response to volume expansion in lesioned animals (-30.4 +/- 2.5% delta RSNA). Thus exogenous AVP augmented cardiopulmonary reflex-mediated inhibition of RSNA due to volume expansion. This effect appeared to be mediated by the V1 AVP receptor and to require the presence of an intact area postrema.

Role of central catecholamines on the potentiation of the baroreflex produced with vasopressin. A study using 6-hydroxydopamine.

This study compares the effect of arginine-vasopressin and phenylephrine on renal sympathetic nerve activity, arterial pressure, and heart rate in vehicle- and intraventricular 6-hydroxydopamine-treated conscious rabbits. In addition, this study examines the involvement of forebrain structures on these variables. In vehicle-treated rabbits, compared to phenylephrine, vasopressin produces a greater decrease in renal sympathetic nerve activity and heart rate for a given increase in pressure. After administration of intraventricular 6-hydroxydopamine, the responses produced with vasopressin are similar to those produced with phenylephrine. Analysis of catecholamine content in the nucleus of the solitary tract, parabrachial nucleus, area postrema, and spinal cord indicates that the only regions of significant catecholamine depletion are in the nucleus of the solitary tract and the spinal cord. Transection at the mid-collicular level does not alter significantly the responses of vasopressin or phenylephrine on renal sympathetic nerve activity or heart rate. This indicates that forebrain structures are not involved in mediating the enhanced buffering effect produced with vasopressin.

Baroreflex control of sympathetic nerve activity after elevations of pressure in conscious rabbits.

The purpose of this study was to assess the effect of rapid baroreceptor resetting on the baroreflex control of renal sympathetic nerve activity in conscious rabbits. Renal sympathetic nerve activity was recorded and used as an index of the efferent limb of the baroreflex. Heart rate and arterial pressure were also recorded. Arterial pressure was raised with either phenylephrine or angiotensin II to a level that eliminated renal sympathetic nerve activity and was maintained at this level for periods of time ranging from 1 to 60 min. On returning pressure to control levels, renal sympathetic nerve activity remained suppressed for up to 90 min, with the duration of the suppression dependent on the magnitude and duration of the pressure stimulus. During this period of suppressed nerve activity, baroreflex curves were generated. The curves produced at this time were also suppressed as compared with control baroreflex curves. With time, the suppressed baroreflex curves returned to control. Further studies were performed to show that the suppression of renal sympathetic nerve activity was mediated via the prolonged increase in baroreceptor afferent activity during the pressure stimulus and was not due to a central effect of phenylephrine. This study indicates that although baroreceptor afferent activity may reset rapidly, there does not appear to be an augmentation of renal sympathetic nerve activity as would be expected.

Interactions of vasopressin with the area postrema in arterial baroreflex function in conscious rabbits.

This study compares the effect of arginine-vasopressin with phenylephrine on arterial pressure, heart rate, and renal sympathetic nerve activity in conscious rabbits with and without functional arterial baroreflexes and in rabbits with lesions of the area postrema. In intact rabbits, progressive infusions of arginine-vasopressin result in large decreases in renal sympathetic nerve activity and heart rate for a given increase in blood pressure as compared to progressive infusions of phenylephrine. In sinoaortic-denervated rabbits, the responses of arterial pressure on heart rate and renal sympathetic nerve activity to both arginine-vasopressin and phenylephrine are markedly attenuated, indicating the necessity for afferent baroreceptor activity in this response. This observation indicates that arginine-vasopressin is acting centrally to enhance the baroreflex. A central site of action of circulating vasopressin may be the area postrema, since it is the only circumventricular organ in the hindbrain. Lesioning the region of the area postrema resulted in a normalization of the responses evoked with arginine-vasopressin and phenylephrine. There was no difference in the phenylephrine responses of arterial pressure on renal sympathetic nerve activity or heart rate in area postrema-lesioned animals, compared to control rabbits. Therefore, we conclude that the area postrema or its surrounding tissue is either a site of action of circulating arginine-vasopressin or contains fibers of passage from another site where arginine-vasopressin acts to enhance baroreflex activity.

Rapid resetting of aortic nerves in conscious rabbits.

The effect of increased arterial pressure on aortic depressor nerve activity was studied in the conscious rabbit. Aortic baroreceptor resetting was observed following 15 min of sustained pressure elevation. At 15 min, there was a significant increase in the threshold arterial pressure for aortic nerve activity, but peak nerve activity did not change. This resulted in an increase in the slope of the pressure-nerve activity relationship. Therefore, except for peak nerve activity, aortic nerve activity was reduced at all pressures following 15 min of sustained pressure elevation. At 30 min, peak nerve activity also increased, resulting in a parallel shift in the pressure-activity curve. The early increase in slope of the pressure-activity relationship may be due to an early resetting of low threshold fibers with a high pressure differential between their threshold pressure and the sustained pressure elevation used to induce resetting. A late resetting of high threshold fibers with a low pressure differential between their threshold pressures and the pressure used to cause resetting of baroreceptors results in a parallel shift in the curve observed at 30 min. These data obtained from multiunit recordings provide unexpected evidence about baroreceptor resetting, which is not apparent from single-unit recordings.