Fine structure of baroreceptor terminals in the carotid sinus of guinea pigs and mice

Summary A light and electron microscopic study was undertaken on the baroreceptor axon terminals in the carotid sinus of guinea pigs and mice, using serial semithin and thin sections.Together with their enveloping Schwann cells, numerous lanceolate axon terminals are organized into a well-defined discoid end organ, referred to as the baroreceptor unit. Baroreceptor units measure 100 to 150 m in diameter and are arranged in a hexagonal pattern. These end organs represent free branched lanceolate mechanoreceptors of complex type (Andres and von Düring, 1973) which belong to the main group of stretch receptors.In the guinea pig the lanceolate terminals enter the media and approach the innermost layers near the intima. In the mouse the terminals are seen to spread in the adventitia and along the medio-adventitial border. Only a few of them penetrate the external elastic layer. Species differences concerning the localization and extent of these visceral mechanoreceptors are discussed, as well as the modified architecture of the sinus wall in the receptor area (elastic segment).Lanceolate terminals form beaded varicosities which are equipped with finger-like or lamellar axoplasmic protrusions. These projections contain a well-differentiated receptor matrix. They are attached to collagen and elastic fibers. The varicosities include densely packed mitochondria, neurotubules, profiles of axoplasmic reticulum, clear and granular vesicles, and striking accumulations of glycogen particles, lamellated bodies and lysosomes. Four types of varicosities are discerned according to their main axoplasmic components. Various types of these varicosities occur within an individual lanceolate terminal.The adrenergic innervation of the carotid sinus was studied by fluorescence histochemistry. In guinea pigs a multilayered wide-meshed plexus of fluorescent fibers occurs in the adventitia where it is closely related to baroreceptor stem fibers. However, adrenergic axons do not enter the media. In mice fluorescent fibers are extremely rare in the adventitia of the carotid sinus.Dedicated to Prof. Dr. Drs.h.c. W. Bargmann on the occasion of his 70th birthdaySupported by a grant from the Deutsche Forschungsgemeinschaft Nr. Bo/525-1. These results were presented in part at the 17. Tagung der Deutschen Gesellschaft für Elektronenmikroskopie, Berlin, Sept. 21.–26., 1975     

Functional asymmetry in carotid sinus cardiac reflexes in humans

The reflex cardiac response to activation (CBA) and inactivation (CBI) of the left and right carotid baroreceptors was studied in 30 healthy subjects, aged between 24 and 38 years. The CBA was evoked by applying negative pressure (from -20 to -60 mmHg) for 10 s to the left and right carotid sinus regions separately or both together, using two small neck capsules. The CBI was produced by applying left and right positive neck pressure (from 20 to 60 mmHg) for 10 s. The blood flow velocity was measured non-invasively with a Doppler scanner placed in the suprasternal notch. Blood flow acceleration was calculated and used as an indication of left cardiac contractility. Heart rate was measured continuously. Differences were found between right and left carotid sinus responses to CBA and CBI. The maximal response of the R-R interval was significantly greater during right CBA than during left CBA (the average gain: R-R.mmHg-1 2.69 ms.mmHg-1 and 1.75 ms.mmHg-1, respectively). Also, the reflex CBI response was significantly greater for the right (3.16 ms.mmHg-1) than for the left (2.22 ms.mmHg-1). The reflex decrease/increase in blood-flow acceleration in response to CBA/CBI was significantly greater during left than during right-sided activation/inactivation. It is suggested that the functional asymmetry was related to differences in right/left-sided cardiac innervation as well as to central ipsilateral projection of the carotid baroreceptor afferents to the nuclei tractus solitarii.     

Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.     

Carotid sinus, aortic and subclavian baroreceptor activities during cardiopulmonary bypass in rabbits.

10Carotid sinus (SIN), aortic (AO) and subclavian (SUB) baroreceptor activities were recorded from intact nerves during experiments using cardiopulmonary bypass in 11 rabbits. These activities (number of impulses/second) were expressed as a percentage of basal activity observed before artificial circulation (AC). The preparation remained in a relative, "stable period" for up to 45 minutes. Then, a progressive decrease occurred in maximal arterial pressure (AP max) in the 11 experiments (fig. 2,4). 20 According to the level of arterial pressure the "stable period", our experiments can be divided into two groups: a) Group I (6 rabbits) with AP max greater than or equal 90 mm Hg; in this group, the correlation coefficients between pressure levels and nervous activities calculated during the period 0-70 min after the onset of AC, were positive (fig. 3) and statistically significant, as we could expect (AO, p less than 0.02; SIN, p less than 0.01; SUB, p less than 0.01). b) Group II (5 rabbits) with AP max less than 90 mm Hg; surprisingly, in this group no positive correlation was found between levels and nervous activities, which were generally very high (fig. 5). 30 Experiments were performed in 18 other rabbits in order to check the nature of the higher activities recorded in group II. These high activities were not of chemoreceptor or efferent origin, and, thus, were thought to be indeed really from baroreceptive fibres. 40 Ten experiments under AC were carried out to test the reactivity of baroreceptors in response to induced increase and decrease of pressure. The responses were qualitatively normal (i.e. an increase of pressure produced an increase in the nervous discharge), but in group II, the operative point was set at a higher level (fig. 6). 50 A possible, time-dependent, shift in the baroreceptor response curve under AC can account for these findings by giving, in some cases the illusion of a negative correlation between baroreceptor activity and arterial pressure (fig. 8). 60 The above mentioned shift in the baroreceptor response curve could be related to a change in sympathetic control of baroreceptors,resulting in a higher activity, and initiating and/or maintaining hypotension.     

Modulation of baroreceptor activity by gene transfer of nitric oxide synthase to carotid sinus adventitia

Administration of nitric oxide (NO) or NO donors to isolated carotid sinus and carotid bodies inhibits the activity of baroreceptor and chemoreceptor afferent nerves. Furthermore, NO synthase (NOS) is present in endothelial cells and in sensory nerves innervating the carotid sinus region. The major goal of this study was to determine whether overexpression of NOS in carotid sinus modulates baroreceptor activity. Rabbits were anesthetized, and adenoviral vectors (5 x 10(8) plaque-forming units) encoding genes for either beta-galactosidase (beta-Gal) or endothelial type III NOS (eNOS) were applied topically to the adventitial surface of one carotid sinus. In some experiments, the NOS inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) was applied to the carotid sinus immediately after the vector. Four to five days later, baroreceptor activity and carotid sinus diameter were measured from the vascularly isolated carotid sinus of the anesthetized rabbits. Transgene expression was confirmed by X-Gal staining of beta-Gal and measurement of NOS activity by citrulline assay. The expression was restricted to the carotid sinus adventitia. Baroreceptor activity was decreased significantly, and the pressure-activity curve was shifted to higher pressures in eNOS-transduced (n = 5) compared with beta-Gal-transduced (n = 5) carotid sinuses. The pressure corresponding to 50% of maximum activity averaged 55 +/- 6 and 76 +/- 7 mmHg in beta-Gal- and eNOS-transduced carotid sinuses, respectively (P < 0.05). Decreased baroreceptor activity was accompanied by a significant increase in carotid diameter in the eNOS-transduced carotid sinuses (n = 5). l-NAME prevented the inhibition of baroreceptor activity and the increase in carotid diameter in eNOS-transduced carotid sinuses (n = 5). We conclude that adenoviral-mediated gene transfer of eNOS to carotid sinus adventitia causes sustained, NO-dependent inhibition of baroreceptor activity and resetting of the baroreceptor function curve to higher pressures.     

激动中枢组胺能受体对应激大鼠颈动脉窦压力感受性反射重调定的影响

应激1周的大鼠,麻醉后弧离双侧颈动脉窦区,将不同窦内压（ISP）与其对应的平均动脉压（MAP）值进行Logistic5个参数曲线拟合。根据所得ISP－MAP关系曲线及其特征参数,分别观察侧脑室(i.c.v.）注射和弧束核（NTS）内注射组胺受体拮抗剂对颈动脉窦压力感受性反射（CSR）的影响,并与相应的非应激CSR水平进行比较。结果如下：（1）应激导致ISP－MAP关系曲线显著全面上移,窦内压和增益（ISP-Gain）关系曲线中部明显下移,反射参数中阈压（TP）、饱和压（SP）、调定点（set point）和最大增益时的窦内压（ISPGmax）值增大,MAP反射变动范围（MAPrange）及反射最大增益（Gmax）减小;（2）I.c.v.H1或H2受体拮抗剂氯苯吡胺（CHL）15μg或西咪替丁（CIM）15μg,在20min内均可明显减弱应激对CSR的上述改变,CIM的这种减弱作用不如CHL的显著;（3）NTS内注射CHL（0.5μg）或CIM（1.5μg）,对应激所致CSR变化的影响与i.c.v.CHL或CIM后的相类似;（4）分别i.c.v.和NTS内注射CHL或CIM后,均不能使应激的CSR水平完全恢复到相应的非应激对照水平。以上结果提示,应激引起CSR重调定,反射敏感性下降;其部分机制可能是激活中枢组胺能系统,通过中枢组胺能受体（H1和H2受体）尤其是H1受体介导而发挥作用;下丘脑－NTS的组胺能通路可能是应激导致CSR重调定的下行通路之一。