Left ventricular reflex control of venous return and systemic vascular capacitance in dogs

The reflex effects of left ventricular distension on venous return, vascular capacitance, vascular resistance, and sympathetic efferent nerve activity were examined in dogs anesthetized with sodium pentobarbital. In addition, the interaction of left ventricular distension and the carotid sinus baroreflex was examined. Vascular capacitance was assessed by measuring changes in systemic blood volume, using extracorporeal circulation with constant cardiac output and constant central venous pressure. Left ventricular distension produced by balloon inflation caused a transient biphasic change in venous return; an initial small increase was followed by a late relatively large decrease. Left ventricular distension increased systemic blood volume by 3.8 +/- 0.6 mL/kg and decreased systemic blood pressure by 27 +/- 2 mmHg (1 mmHg = 133.3 Pa) at an isolated carotid sinus pressure of 50 mmHg. These changes were accompanied by a simultaneous decrease in sympathetic efferent nerve activity. When the carotid sinus pressure was increased to 125 and 200 mmHg, these responses were attenuated. It is suggested that left ventricular mechanoreceptors and carotid baroreceptors contribute importantly to the control of venous return and vascular capacitance.     

The efferent sympathetic activity of the rabbit renal nerve during local application of adrenaline to the carotid sinus]

Adrenalin solution (1:1000) administered at the carotid sinus, through excitation of the depressoric C-fibre system of the carotid nerve, induces a strong, lasting reflectoric decrease of arterial pressure with slowing heart rate, associated with an almost complete inhibition of the efferent sympathetic activity of the renal nerve. The efferent sympathetic activity, arterial blood pressure and heart rate, both at the onset and at the height of adrenalin action, show corresponding activity changes: the relative inhibition of the sympathetic nerve is strongest correlated with the depressoric blood-pressure effect, while the decrease of heart rate, related to the initial activity, is least pronounced.     

The role of the active center of the enzyme in the triggering mechanism of the compensatory reaction to plasmin

The participation of plasmin active site in the trigger's mechanisms of the compensatory reaction of haemostasis system on this enzyme was studied in the experiments on white rats and rabbits using intravenous injection and perfusion of the humorally isolated carotid sinus are with intact innervation. Native enzyme, the enzyme with reversibly (acylated plasmin) and irreversibly (diisopropylphosphoryl plasmin) blocked active site were used. It was ascertained that the development of the compensatory reaction of haemostasis system on plasmin, manifested by hypercoagulation and depression of fibrinolysis, is conditioned by the proteolytic activation of the vascular wall receptors.     

Influence of substance P on carotid sinus nerve baro- and chemoreceptor activity in rabbits.

Substance P (SP) is abundant in the carotid sinus nerve (CSN) and has been implicated in baro- and chemoreceptor reflexes. We examined the effect of SP on blood pressure, heart rate, phrenic nerve activity, hindlimb perfusion pressure, and cardiac contractile strength in urethane-anesthetized rabbits with bilaterally cut cervical sympathetic, vagus, and aortic depressor nerves. Retrograde simultaneous injection of SP (0.5-2.7 micrograms/kg in 0.2-0.3 ml saline) into both carotid sinus areas via the internal carotid arteries decreased blood pressure (by 56%), heart rate (by 13%), cardiac contractility (by 25%) and phrenic nerve activity (by 77%). The effect on hindlimb perfusion pressure was variable. There was both a reflex effect and direct hindlimb vasodilation. In another group of rabbits, the carotid sinus areas were vascularly isolated and perfused with SP (0.19 micrograms/min dissolved in Locke's solution) or Locke's solution alone for 5 min. While carotid sinus perfusion pressure was maintained in the range of 80-120 mmHg, mean arterial blood pressure, heart rate, and unit activity from the CSN were recorded. SP increased the activity of 11 of 18 baroreceptor fibers and inhibited all of 20 chemoreceptor fibers. SP decreased mean arterial blood pressure and heart rate, but the changes were less than those obtained with injection of SP into nonisolated carotid sinus arteries because systemic effects of SP, which in some cases counteracted the reflex effects, were eliminated.     

EFFECTS OF SINUS NERVE STIMULATION ON CAROTID BODY GLOMUS CELLS

The sinus nerve or sympathetic trunk was stimulated unilaterally in one group of adult cats or Syrian hamsters while in another group the sinus nerve or sympathetic trunk was cut unilaterally and the animals were given reserpine. In a third group, atropine was administered prior to sinus nerve stimulation. All tissues were processed for the detection of primary monoamines. The carotid bodies on the operated sides were compared with those on the unoperated sides of the same animal in order to determine if amine depletion occurred following the experimental procedures. After sinus nerve stimulation alone, the density of the granules in the glomus cells was decreased, but changes were not noted in the granules following sympathetic nerve stimulation. Sinus nerve stimulation after atropine administration resulted in no change in granule density. Sinus nerve transection followed by reserpine treatment resulted in a greater decrease in granule density on the unoperated than on the operated side. Transection of the sympathetic components to the carotid body followed by reserpine injections resulted in a decrease in granule density in the glomus cells on both the operated and unoperated sides. These results suggest that the sinus nerve must be intact for reserpine to exert an effect and that the sinus nerve may contain efferent fibers which modulate amine secretion.     

The inhibition of efferent sympathetic activity by means of pressure stimulation of the carotid sinus pressoreceptors]

The influence of pressure stimulation of a barorecptor upon the activity of the sympathetic nerve branch terminating in the wall of the contralateral carotid bifurcation was studied on narcotized dogs. The potential activity of this branch is of efferent nature. On the average, 570 msec after the pressure load applied to the opposite carotid sinus preparation, a silent period occurred. The duration of this silent period and the activity of the sympathetic nerve branch depend on the internal pressure of the preparation. The influence of different structures (central and peripheral) on latency, total and partial inhibition of the sympathetic activity are discussed.     

Baroreceptor control of pressure-flow relationships during hypoxemia

In the absence of peripheral chemoreceptors, the effects of graded hypoxemia on the carotid sinus control of central and regional hemodynamics were studied in anesthetized mongrel dogs. Baroreceptor stimulation was effected by carotid sinus isolation and perfusion under controlled pressure. Blood flows were measured in the aorta and the celiac, mesenteric, left renal, and right iliac arteries. Carotid sinus reflex set-point pressures were well maintained until hypoxemia was severe. Carotid sinus reflex set-point gain was maximal during mild hypoxemia. Reflex operating point regional flows were unaffected by hypoxemia. A factorial analysis of overall reflex increases in mean aortic pressure, flow, and power during reduced baroreceptor stimulation showed potentiation by increasing hypoxemia. Corresponding effects of baroreceptor stimulation and hypoxemia on aortic resistance and heart rate were additive. Celiac, renal, and iliac blood flows increased during both hypoxemia and reduced baroreceptor stimulation. Only in the celiac bed were blood flow changes independent of concomitant changes in cardiac output. Thus, at maximum sympathetic stimulation (low carotid sinus pressure) during hypoxemia, the cardiovascular system maintained both central and regional blood flows at high systemic blood pressures independent of the peripheral chemoreceptors.     

Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity

Background

Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity.

Methods

Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG.

Results

Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls.

Conclusions

Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to understanding the mechanisms behind the symptomatic presentation of carotid sinus hypersensitivity.     

Opposite effects of iv amiodarone on cardiovascular vagal and sympathetic efferent activities in rats

It is unknown whether amiodarone exerts a direct central action on the cardiovascular autonomic nervous system. This study was designed to evaluate the effects of acute amiodarone administration on vagal and sympathetic efferent nerve discharges. Experiments were carried out in 25 decerebrate unanesthetized rats. In one group, vagal activity was recorded from preganglionic fibers isolated from the cervical vagus nerve. In another group, sympathetic recordings were obtained from fibers isolated from the cervical sympathetic trunk in intact conditions or after barodenervation. Recordings were performed before and for 60 min after amiodarone (50 mg/kg iv) administration. In all groups, amiodarone induced bradycardia and hypotension. Vagal activity increased immediately, reaching a significant difference after 20 min (260 +/- 131% from 16.4 +/- 3.3 spikes/s) and was unmodified by the barodenervation. At difference, sympathetic activity after an initial and short-lasting increase (150 +/- 83% from 24.8 +/- 5.7 spikes/s) began to decrease significantly after 20 min (36 +/- 17%) throughout the experiment. The initial increase in sympathetic activity was not observed in barodenervated animals. These changes in vagal and sympathetic activity could play an important role in contributing to the antiarrhythmic action of amiodarone.     

The influence of carotid sinus pressure on plasma atrial natriuretic peptide in anaesthetized rabbits

The effect of changes in carotid sinus perfusion pressure on plasma immunoreactive atrial natriuretic peptide (IR-ANP) was examined in anaesthetized rabbits, and the role of arterial pressure in mediating the changes in IR-ANP was assessed. Plasma IR-ANP was significantly greater (101.7 +/- 24.3 pg ml-1) when carotid sinus pressure was 60 mmHg than when it was 160 mmHg (27.1 +/- 8.6 pg ml-1). Mean arterial pressure (MAP) was significantly greater when carotid sinus pressure was controlled at 60 mmHg compared to when it was 160 mmHg, but right atrial pressure (RAP) was not significantly different at the two carotid sinus pressures. The administration of hexamethonium attenuated the changes in MAP and heart rate (HR) which occurred in response to alterations in carotid sinus pressure, and abolished the change in plasma IR-ANP. The results suggest that an inverse relationship exists between carotid sinus pressure and plasma IR-ANP, and that the release of ANP in response to a reduction of carotid sinus pressure is mediated by the associated haemodynamic changes.     

Differential dynamic baroreflex regulation of cardiac and renal sympathetic nerve activities

Although regional difference in sympathetic efferent nerve activity has been well investigated, whether this regional difference exists in the dynamic baroreflex regulation of sympathetic nerve activity remains uncertain. In anesthetized, vagotomized, and aortic-denervated rabbits, we isolated carotid sinuses and randomly perturbed intracarotid sinus pressure (CSP) while simultaneously recording cardiac (CSNA) and renal sympathetic nerve activities (RSNA). The neural arc transfer function from CSP to CSNA and that from CSP to RSNA revealed high-pass characteristics. The increasing slope of the transfer gain in the frequencies between 0.03 and 0.3 Hz was significantly greater for CSNA than for RSNA (2.96 +/- 0.72 vs. 1.64 +/- 0.73 dB/octave, P < 0.01, n = 9). The difference was hardly explained by the difference in static nonlinear characteristics of CSP-CSNA and CSP-RSNA relationships or by the difference in conduction velocities in the multifiber recording. These results indicate that the central processing in the brain stem differs between CSNA and RSNA. The neural arc of the baroreflex may exert differential effects on the heart and kidney in response to dynamic baroreflex activation.     

In vitro perfused-superfused cat carotid body for physiological and pharmacological studies

An in vitro perfused carotid body preparation was developed to study its chemosensory responses to physiological and pharmacological stimuli. The carotid bifurcation with the carotid body was vascularly isolated and excised from pentobarbital sodium-anesthetized cats. The CB was perfused in a chamber by gravity (80 Torr) with modified Tyrode's solution (N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-NaOH at pH 7.40) equilibrated at a given Po2 and superfused with the same medium at (Po2 of 20 Torr). The temperature was maintained at 35.5 +/- 0.5 degrees C. The frequency of chemosensory discharges (CD) was recorded from the whole carotid sinus nerve (n = 24), and the responses were tested by repeated interruptions of perfusate flow (SF), perfusion with hypoxic medium, and injections of nicotine and cyanide (0.1 nmol to 1 mumol) and hypercapnic medium. During hyperoxic perfusion, SF resulted in a sigmoidal increase in CD, reaching a maximum that was 23.6 +/- 4.4-fold greater than the basal activity. Restoration of flow returned CD promptly to basal values. After normoxic perfusion, SF led to a similar maximal activity more rapidly, but the duration was shorter. Reduction of the perfusate PO2 (Po2 from 450 Torr to 150, 30, and less than 10 Torr) caused a nonlinear increase in CD. CO2 stimuli (PCo2 38-110 Torr) resulted in a linear increase in CD. Nicotine or cyanide increased CD in a dose-dependent manner. The preparation retained its initial responsiveness for 2-3 h, making extensive experimental studies feasible.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Innervation of the carotid body. An experimental quantitative study

The innervation of the carotid body in the cat was studied by means of light- and electron-microscopic techniques. Sinus nerve resection, glossopharyngeal resection, bilateral cervical sympathectomy, excisions of two nerves, and injection of 6-hydroxydopamine (6-OH-DA) were performed in different groups of animals. It was found that resection of the sinus nerve produces a rapid phase of degeneration of intralobular fibers and synaptic boutons, followed by a reinnervation with a progressive reappearance of these elements. This reinnervation is retarded by sympathectomy and prevented by 6-OH-DA. It is therefore concluded that reinnervation is due to collateral regeneration of nearby sympathetic fibers. Resection of the sinus nerve produces an increase in the number of argentaffin cells and dense-cored vesicles in the cytoplasm of principal cells. These findings suggest the existence of efferent synaptic contacts between this nerve and principal cells. Part of the intralobular fibers and synaptic boutons degenerate after bilateral sympathectomy demonstrating that sympathetic axons connect synaptically to the principal cells. Sympathetic fibers reach the carotid body, not only from branches of the cervical plexuses but also from fibers running in the adventitia of the common carotid artery, and via glossopharyngeal and sinus nerves. The vagus nerve contributes a few fibers to the parenchymal lobules of the carotid body.     

腺苷易化大鼠颈动脉窦压力感受器的活动

在36只麻醉大鼠,以隔离灌流颈动脉窦区记录窦神经传入放电的方法观察了腺苷（adenosine,Ado）对颈动脉窦压力感受器传入放电的影响。所得结果如下：（1）以75μmol／LAdo隔离灌流大鼠左侧颈动脉窦区时,窦内压-窦神经传入放电积分（ISP－ISNA）关系曲线向左上方移位,曲线最大斜率（PS）由（18．75±0．12）％／kPa增至（22．21±0．11）％／kPa（P＜0．001）,最大积分值（PIV）由（209．83±2．57）％增至（239．17±1．75）％;阈压（TP）和饱和压（SP）则分别从（8．57±0．24）和（22．99±0．34）下降至（7．15±0．23）kPa（P＜0．001）和（21．21±0,43）kPa（P＜0．01）。再分别以125和175μmol／LAdo灌流,机能曲线进一步向左上方移位,PS、TP和SP的变化均呈明显的剂量依赖性。（2）用腺苷选择性A1受体拮抗剂8－cyclopentyl－1,3－dipropylxanthine（0．134mmol／L）预处理后,Ado的上述效应即被阻断。（3）先给予KATP通道阻断剂格列苯脲（10μmol／L）亦可取消腔苷对窦神经传入放电的影响。结果表明,在体隔离灌流大鼠颈动脉窦区条件下,Ado对颈动脉窦压力感受器活动有易化作用,此作用似与腺苷A1受体介导的KATP通道开放有关。     

颈动脉窦内压的变化速率对反射性降压效应的影响

在成年狗身上制备右侧孤离颈动脉窦,借助灌流装置用饱和氧的任氏液对其进行灌流。灌流压为搏动性的。通过改变每搏泵出量、灌流管道的阻力和弹性来调节灌流压及其变化速率。用多导生理记录仪同步记录股动脉血压、窦内灌流压及其变化速率。本文主要观察窦内压的变化速率对降压反射的影响。在8只狗身上共进行了93次实验。结果表明,在窦内压相同的情况下,灌流压的上升速率愈快,降压效应愈明显,而其下降速率则无显著作用。已有资料证明搏动性窦内压所引起的降压效应较非搏动性压力更为明显。由此可见,狗的颈动脉窦压力感受器不仅对搏动性压力而且对其上升的变化速率也很敏感。     

Alpha-adrenergic receptor modulation of the intrathoracic efferent sympathetic nervous system regulating the canine heart

The augmentation of ventricular inotropism induced by electrical stimulation of acutely decentralized efferent sympathetic preganglionic axons was reduced, but still present, following administration of hexamethonium (10 mg/kg i.v.). While hexamethonium continued to be administered, the cardiac augmentations so induced were enhanced significantly following administration of the alpha-adrenergic receptor blocking agent, phentolamine myselate (1 mg/kg i.v.). Stimulation of the sympathetic efferent postganglionic axons in cardiopulmonary nerves induced cardiac augmentations that were unchanged following administration of these agents singly or together. The cardiac augmentations induced by stimulation of efferent preganglionic sympathetic axons were unchanged when phentolamine was administered alone. The augmentations of cardiac inotropism induced by efferent postganglionic sympathetic axonal stimulation were decreased following local administration of the beta-adrenergic antagonist timolol into the ipsilateral stellate and middle cervical ganglia. Thereafter, these augmentations were unchanged following the subsequent intravenous administration of phentolamine. It is concluded that the activation of cardiac neurons in the stellate and middle cervical ganglia by stimulation of efferent preganglionic sympathetic axons can be modified by alpha-adrenergic receptors and that these effects are dependent upon beta-adrenergic receptors, not nicotinic ones, in intrathoracic ganglia.     

A method of evoking fast baroreceptor responses for the measurement of the baroreflex latency.

A method for measurement of latency in the baroreflex is described. Standardised square pressure pulse was applied to the isolated carotid sinus and simultaneous recordings of the carotid sinus nerve or sympathetic fibers were performed. Relatively short time of the increase of the pressure makes possible more exact measurements of latency in the baroreflex than other known methods used for this purpose.     

The action of ADP ribose on the mechanical and bioelectrical activity of the frog heart]

In the frog isolated heart, cyclic perfusion of ADP-ribose induced a dose-dependent decrease in the heart rate and the contraction force, a decrease in the AP duration as well as in the rate of rise in the sinus node. It also shortened the atrial AP and exerted no significant effect upon multicellular ventricular preparations. In conditions of systemic administration in unanesthetised frogs, the ADP-ribose induced a reversible increase in the heart rate due, probably, to a sympathetic effect.     

Limb vasodilation provoked by stimulation of the carotid sinus. Importance of histaminergy in the dog

The vasodilator reflex induced by baroreceptor stimulation was studied on the hindlimbs of the dog. The reflex was induced by norepinephrine (1 microgram/kg) either by intravenous injection or by direct injection into the carotid sinus. In other experiences, the baroreceptor stimulation was obtained by distension of the sinus by rapid injection of 100 ml of physiological serum. The vascular response was studied by recording the hindlimbs blood flow. One of the limbs was previously pretreated by mepyramine and cimetidine (blockage of histaminergic H1 and H2 receptors). During the first minute after the baroreceptor stimulation, blood samples were collected from the venous blood of hindlimbs for histamine assay (fluorometric assay). Our results show: a much lower vasodilation on the limb pretreated by histamine antagonist, a significant increase during the reflex vasodilation of histamine blood levels measured in the efferent blood of hindlimbs. These results, obtained in experimental conditions as physiological as possible (blood perfusion of the limbs with "natural" hemodynamic parameters) permit to conclude that the vasodilation induced by baroreceptor reflex is at least partially histaminergic in the dog.