Changes in renal sympathetic outflow during hypotensive haemorrhage in rats

The goal of this study was to investigate changes in renal sympathetic outflow during hypotensive haemorrhage. Normotensive Wistar-Kyoto rats were anaesthetized with chloralose (50 mg kg-1) and bled to an arterial blood pressure of 50 mmHg for 30 min. Changes in heart rate (HR) and renal nerve activity (RNA) were registered. The hypotensive haemorrhage induced a short-lasting sympathetic excitation that was followed within 5-10 min by a powerful sympathetic inhibition and bradycardia. The average maximal decrease in sympathetic activity was 65% and the maximal decrease in heart rate was 45 beats min-1. There was a close correlation between changes in heart rate and renal sympathetic activity. The marked depressor response was due at least in part to activation of vagal afferents because the depressor responses were acutely reversed by bilateral cervical vagotomy. As cardiac afferents are known to be activated by prostaglandins and bradykinins, and these agents are released by myocardial ischaemia, haemorrhage was repeated after use of indomethacin and aprotinin (a protein inhibitor decreasing bradykinin formation), and a marked sympathetic inhibition could still be elicited upon haemorrhage. We therefore suggest that the likely mechanism for activation of the vagal afferents is a squeezing of the myocardium when the heart has to contract around an almost empty chamber. In conclusion, this study demonstrated that hypotensive haemorrhage triggers profound inhibition of RNA in rats and that this sympathoinhibition is mediated primarily by mechanically sensitive cardiac vagal afferents.     

Contrasting reflex influences of cardiac afferent nerves during coronary occlusion

Afferent neurons contained within cardiac sympathetic nerves may have important influences on the circulation when activated during myocardial ischemia. Although such activation is known to reflexly excite upper thoracic sympathetic efferent neurons, effects on other components of sympathetic outflow are unknown. Therefore, cardiac sympathetic afferent nerves were stimulated by occlusion of coronary arteries to investigate their reflex influences on renal sympathetic nerve activity and systemic arterial blood pressure. Responses were observed in anesthetized cats in which sympathetic and/or vagal cardiac afferent nerves remained intact and arterial baroreceptors remained intact or had been denervated. Stimulating sympathetic afferent neurons caused excitation of renal nerve activity, which was accompanied by variable changes in arterial pressure. Stimulation of vagal afferents by coronary occlusion consistently produced inhibition of renal nerve activity and marked depressor responses. When both components of cardiac innervation remained intact, increases or decreases in renal nerve activity and blood pressure were elicited by coronary artery occlusion in the presence or absence of arterial baroreceptors. These results illustrate that cardiac sympathetic afferent nerves can contribute significantly to cardiovascular control during myocardial ischemia.     

The effects of stimulation of the left atrial receptors on sympathetic efferent nerve activity

1. Activation of left atrial receptors by distension of balloons at the pulmonary vein-atrial junctions caused an increase in the cardiac sympathetic nerve activity, a decrease in the renal sympathetic nerve activity, and no change in the lumbar and splenic sympathetic nerve activity.2. The cardiac and renal nerve responses to balloon distension were abolished by vagal blockade in the neck.3. The results provide additional evidence that the reflex increase in the heart rate following stimulation of the left atrial receptors is mediated by selective activation of cardiac sympathetic nerve fibres.4. The inhibitory effect of atrial receptor activation on the renal sympathetic nerve activity suggests that a neural factor, possibly involving renal haemodynamics, may be a component of the diuretic response to the activation of the left atrial receptors.5. The results provide further evidence for the selective nature of the pattern of reflex responses to left atrial receptor activation and show for the first time a directionally fractionated response from sympathetic efferent neurones.     

Responses of neurons in paraventricular nucleus to activation of cardiac afferents and acute myocardial ischaemia in rats

Stimulation of cardiac sympathetic afferents increases sympathetic outflow and blood pressure. Chemicals released during myocardial ischaemia activate cardiac afferents. This study was to determine the responses of neurons in paraventricular nucleus (PVN) to the cardiac afferent activation caused by exogenous chemicals or myocardial ischaemia using an extracellular single-unit recording method. Rats were anaesthetized and underwent bilateral cervical vagal denervation (VD) and carotid and aortic baroreceptor denervation (BD). In 196 spontaneously active neurons in parvicellular PVN, 60 (30.6%), 36 (18.4%) and 91 (46.4%) neurons were respectively sensitive, mildly sensitive and insensitive to capsaicin, while nine (4.6%) neurons showed inhibitory responses to capsaicin. Epicardial application of capsaicin activated capsaicin-sensitive neurons in the PVN and increased mean arterial pressure. These neurons were also sensitive to exogenous bradykinin, adenosine and H(2)O(2). The neuron response is not secondary to a capsaicin-induced increase in mean arterial pressure because a similar degree of pressor response induced by aortic coarctation did not increase the neuron activity. Compared with intact rats, VD or BD or combined VD and BD increased the response of capsaicin-sensitive neurons to epicardial application of capsaicin, while stimulation of vagal afferents inhibited the response. Myocardial ischaemia caused increases in the activity of capsaicin-sensitive neurons and renal sympathetic nerve activity. The results indicate that chemical stimulation of cardiac sympathetic afferents activates capsaicin-sensitive neurons in parvicellular PVN, which is inhibited by the afferent activities of vagi and arterial baroreceptors. Acute myocardial ischaemia activates capsaicin-sensitive neurons in PVN and enhances sympathetic outflow.     

Myocardial ischemia recruits mechanically insensitive cardiac sympathetic afferents in cats

Chest pain caused by myocardial ischemia is mediated by cardiac sympathetic afferents. Although silent nociceptors exist in somatic structures and some visceral organs, their presence in the heart remains uncertain. The present study examined the presence and the functional characteristics of mechanically insensitive cardiac sympathetic afferents using an electrical search technique. Single-unit activity of afferents innervating the left ventricle was recorded from the sympathetic chain in anesthetized cats. Cardiac afferents were identified initially with a stimulating electrode placed on the surface of the heart. Responses of cardiac afferents to mechanical stimuli, 5 min of myocardial ischemia, and topical application of bradykinin (1-10 microg/ml) and lactic acid (10-50 microg/ml) were then determined. Ischemia activated all 38 mechanically insensitive afferents and 17 of 25 mechanically sensitive afferents. The mechanically sensitive afferents typically were spontaneously active and had a smaller receptive field and a slightly faster conduction velocity. On the other hand, the mechanically insensitive afferents were slow conducting C fibers and had a large electrical receptive field on the epicardium. The response of 38 mechanically insensitive afferents to ischemia [2.83 +/- 0.14 (SD) imp/s] was significantly greater than that of 17 mechanically sensitive afferents (from 0.41 +/- 0.05 to 0.74 +/- 0.15 imp/s). The mechanically insensitive afferents also exhibited a greater response to topical application of bradykinin or lactic acid in a concentration-dependent manner. This study provides important new evidence that the heart is innervated by silent sympathetic afferents, which are activated profoundly by myocardial ischemia. These data also suggest that the mechanically insensitive sympathetic afferents may function as cardiac nociceptors.     

Ingrowth of sympathetic innervation occurs concomitantly with a decrease of ANP in the growing rat cardiac ventricles

The relationship between the immunohistochemical expression of atrial natriuretic peptide and the occurrence of sympathetic nerve fibres, as visualized by staining for tyrosine hydroxylase, in the growing rat heart was evaluated. Rats were investigated at four different stages from birth to 21 days postnatally. The effects of chemical destruction of sympathetic nerve terminals in neonatal rats on the cardiac atrial natriuretic peptide content were furthermore examined by use of radioimmunoassay. There was in principle a reciprocal pattern of immunoreaction for atrial natriuretic peptide and tyrosine hydroxylase positive innervation in the ventricular myocardium, atrial natriuretic peptide reaction becoming less and less pronounced with the ingrowth of innervation positive for tyrosine hydroxylase. Furthermore, in the peripheral Purkinje fibre network, there was a marked atrial natriuretic peptide immunoexpression and scarce or no nerve fibres throughout the examination period. The radioimmunoassay measurements showed that chemical sympathectomy lead to elevated cardiac levels of atrial natriuretic peptide. The study shows that sympathetic innervation grows into the ventricular parts concomitantly with the occurrence of a decline in atrial natriuretic peptide expression during development of the heart. Furthermore, it is shown that a reversion of the in growth of sympathetic innervation by destruction of cardiac sympathetic nerves at an early stage leads to increased levels of atrial natriuretic peptide in the heart. The results give new evidence to the phenomenon that the atrial natriuretic peptide levels in the ventricular myocardium and the peripheral parts of the conduction system are under influence of the presence of sympathetic innervation. Accepted: 25 July 2000     

Role of cardiac sympathetics in the tonic circulatory restraint by vagal afferents.

In anesthetized cats with aortic nerves sectioned and carotid arteries occluded, we determined the role of cardiac sympathetic nerves on the tonic inhibitory restraint by cardiac vagal afferents on the cardiovascular system. The effect of afferent vagal blockade on mean arterial pressure and cardiac contractility was determined when sympathetic tone to the heart was altered. Bilateral cardiac sympathectomy produced a significant decrease in left ventricular dP/dt and attenuated the arterial pressure response to afferent vagal cold block to less than 40% of the control. The increase in dP/dt normally observed with vagal blockade was also reduced significantly. Increasing dP/dt by efferent stimulation of cardiac sympathetic nerves restored the arterial pressure response to vagal blockade to near control levels. While the vagal inhibitory activity appeared to be dependent on the resting dP/dt, left ventricular peak pressure did not seem to be contributing to the reflex. Thus, the inhibitory effects of vagally mediated reflexes from the heart which contribute to arterial pressure regulation appear to be influenced by changes in cardiac contractility induced by cardiac sympathetic nerve stimulation.     

Atrial ganglionated plexi stimulation may be an effective therapeutic tool for the treatment of heart failure

An autonomic imbalance, i.e., increased sympathetic tone and/or decreased parasympathetic tone is a critical characteristic of heart failure, which is associated with progressive ventricular remodeling, ventricular arrhythmia generation and disease progression. Increasing cardiac parasympathetic tone by vagus nerve stimulation has been shown to significantly improve heart failure symptoms, hemodynamics, left ventricular function and quality of life. However, cervical surgery is needed to position vagal stimulation electrode and vagus nerve stimulation may also cause some undesired side effects. Our recent studies showed that ablation of the main atrial ganglionated plexi (GP) facilitated the occurrence of ventricular arrhythmias in acute myocardial ischemic heart while low-intensity atrial GP stimulation inhibited the occurrence of ventricular arrhythmias during acute myocardial ischemia and ischemia reperfusion. Based on these results, we hypothesize that atrial GP stimulation may ameliorate autonomic dysfunction in heart failure, inhibit heart failure progression and improve heart failure prognosis.     

Atrial natriuretic hormones — Thirty years after the discovery of atrial volume receptors

Summary Twenty-five years after the discoveries of the existence of atrial granules and of volume receptors in the heart atria the search for natriuretic hormones has led to the isolation and identification of the atrial natriuretic factors (ANF) now considered as a hormonal system. These peptides are probably synthesized and stored in the Golgi apparatus of cardiac myocytes and are released in response to atrial wall stretch following acute plasma volume expansion and increased central blood volume, e.g., during head-out water immersion, in arterial hypertension, or increased left and/or right atrial pressure in cardiac failure, but also possibly in response to increased frequency of myocardial contractions, e.g. in paroxysmal tachycardia. The mechanisms of the renal action of these potent natriuretic hormones are not yet precisely known. Increased GFR may contribute to the initial rise in urinary sodium excretion and increased renal medullary blood flow to the later phase of natriuresis. The proximal tubule, the thin descending and the ascending limb of Henle's loop and especially the medullary collecting tubule were so far incriminated as tubular sites of action of ANF. Finally, recycling of sodium in medullary tissue and secretion of sodium via back-flux from the interstitium into the medullary collecting tubule are postulated to result in the hypernatric urine observed after ANF administration. Direct suppression of the secretion of renin, aldosterone, vasopressin, and vasopressin-stimulated cAMP synthesis may also contribute to its diuretic, natriuretic, and antihypertensive effects. The renal hemodynamic and tubular as well as the adrenal and systemic vascular effects are related to enhanced cGMP synthesis in medium-sized arterial vessels, in glomeruli and specific tubular segments, and in adrenal tissue, and may be calcium dependent. Specific ANF-binding sites were detected in these target organs. Although increased ANF release was observed in response to atrial distension in various disease states, which may contribute to renal sodium elimination in human hypertension and congestive heart failure, further studies are needed to identify its precise physiological and pathophysiological significance.Abbreviations ACTH Adrenocorticotropic hormone - ANF Atrial natriuretic factor - AVP Arginine vasopressin - cAMP Cyclic adenosine monophosphate - cGMP Cyclic guanosine monophosphate - d-DAVP d-Desamino arginine vasopressin - DOCA Deoxycorticosterone acetate - ECFV Extracellular fluid volume - GFR Glomerular filtration rate - PAH Paraaminohippurate - PG Prostaglandin - PRA Plasma renin activity - RBF Renal blood flow - SNGFR Single nephron GFR Dedicated to Prof. Dr. F. Krück on the occasion of his 65th birthday     

Undiscovered role of endogenous thromboxane A2 in activation of cardiac sympathetic afferents during ischaemia

Myocardial ischaemia activates blood platelets, which in turn stimulate cardiac sympathetic afferents, leading to chest pain and sympathoexcitatory reflex cardiovascular responses. Previous studies have shown that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents, and that thromboxane A(2) (TxA(2)) is one of the mediators released from activated platelets during myocardial ischaemia. The present study tested the hypothesis that endogenous TxA(2) stimulates cardiac afferents during ischaemia through direct activation of TxA(2) (TP) receptors coupled with the phospholipase C-protein kinase C (PLC-PKC) cellular pathway. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicantes (T(2)-T(5)) in anaesthetized cats. Single fields of 39 afferents (conduction velocity = 0.27-3.65 m s(-1)) were identified in the left or right ventricle initially with mechanical stimulation and confirmed with a stimulating electrode. Five minutes of myocardial ischaemia stimulated all 39 cardiac afferents (8 Adelta-, 31 C-fibres) and the responses of these 39 afferents to chemical stimuli were further studied in the following four protocols. In the first protocol, 2.5, 5 and 10 microg of the TxA(2) mimetic, U46619, injected into the left atrium (LA), stimulated seven ischaemically sensitive cardiac afferents in a dose-dependent manner. Second, BM13,177, a selective TxA(2) receptor antagonist, abolished the responses of six afferents to 5 microg of U46619 injected into the left atrium and attenuated the ischaemia-related increase in activity of seven other afferents by 44%. In contrast, cardiac afferents, in the absence of TP receptor blockade responded consistently to repeated administration of U46619 (n = 6) and to recurrent myocardial ischaemia (n = 7). In the fourth protocol, administration of PKC-(19-36), a selective PKC inhibitor, attenuated the responses of six other cardiac afferents to U46619 by 38%. Finally, using an immunohistochemical staining approach, we observed that TP receptors were expressed in cardiac sensory neurons in thoracic dorsal root ganglia. Taken together, these data indicate that endogenous TxA(2) contributes to the activation of cardiac afferents during myocardial ischaemia through direct stimulation of TP receptors probably located in the cardiac sensory nervous system and that the stimulating effect of TxA(2) on cardiac afferents is dependent, at least in part, upon the PLC-PKC cellular pathway.     

Influence of intravenous infusion on heart rate, sympathetic and vagal efferentation and left atrial and aortic baroreceptor activity in dogs

The influence of 42 i.v. infusions of saline on heart rate, sympathetic and vagal cardiac efferent activity and on the aortic baroreceptor and left atrial B-type nerve impulse activity was studied in 32 morphine-chloralose anesthetized dogs. The responses in heart rate were tachycardic in 31 infusions and bradycardic in 11 infusions. In tachycardia, sympathetic activity increased in a majority of the cases but also decreases and nonsignificant changes were observed. Vagal efferentation decreased in most of the cases but also nonsignificant changes or increases in activity occurred. Sympathetic efferentation mainly decreased in bradycardic responses while vagal efferentation diverged in different directions in its nerve activity rate. The ratio of sympathetic to vagal impulses significantly correlated to the heart rate in most of the cases in tachycardia but not in bradycardia. It is concluded that sympathetic and vagal cardiac efferentation plays a significant role in heart rate regulation in volume load-induced tachycardia but in bradycardia only the changes in sympathetic cardiac efferentation are important in respect to heart rate changes. The aortic baroreceptor and left atrial B-type receptor activity rate increased both in tachycardia and bradycardia. Changes in the activities of these receptors do not explain the different heart rate responses. It is supposed that bradycardic responses result from changes in cardiac contraction associated with some reflex mechanism suppressing the excitatory influence of the activity of atrial receptors on sympathetic cardiac efferentation.     

Post-infarct cardiac sympathetic hyperactivity regulates galanin expression

The neuropeptide galanin is elevated in the cardiac sympathetic innervation after myocardial infarction (MI). Galanin inhibits vagal transmission and may support the regeneration of sympathetic nerves, thereby contributing to the development of arrhythmia and sudden cardiac death after MI. The reason for increased galanin production in sympathetic neurons after myocardial infarction is not known. Cardiac sympathetic neurons are activated chronically after cardiac ischemia–reperfusion, and activation of sympathetic neurons in culture stimulates galanin expression. Therefore, we tested the hypothesis that increased sympathetic nerve activity stimulates galanin expression in cardiac sympathetic neurons after myocardial infarction. To test this hypothesis we used TGR(ASrAOGEN) transgenic rats, which lack brain angiotensinogen and do not exhibit post-infarct sympathetic hyperactivity. Hearts and stellate ganglia were collected 1 week after ischemia–reperfusion. Galanin mRNA was quantified by real-time PCR and peptide content was assayed by enzyme-linked immunosorbent assay. Galanin mRNA increased approximately 3-fold after MI in cardiac sympathetic neurons of both genotypes compared to unoperated and sham controls. Left ventricular galanin content, however, increased after MI only in Sprague–Dawley rats and not in AOGEN rats. These data suggest that post-infarct cardiac sympathetic hyperactivity stimulates galanin peptide production but is not required for increased galanin mRNA expression.     

Post-infarct cardiac sympathetic hyperactivity regulates galanin expression

The neuropeptide galanin is elevated in the cardiac sympathetic innervation after myocardial infarction (MI). Galanin inhibits vagal transmission and may support the regeneration of sympathetic nerves, thereby contributing to the development of arrhythmia and sudden cardiac death after MI. The reason for increased galanin production in sympathetic neurons after myocardial infarction is not known. Cardiac sympathetic neurons are activated chronically after cardiac ischemia-reperfusion, and activation of sympathetic neurons in culture stimulates galanin expression. Therefore, we tested the hypothesis that increased sympathetic nerve activity stimulates galanin expression in cardiac sympathetic neurons after myocardial infarction. To test this hypothesis we used TGR(ASrAOGEN) transgenic rats, which lack brain angiotensinogen and do not exhibit post-infarct sympathetic hyperactivity. Hearts and stellate ganglia were collected 1 week after ischemia-reperfusion. Galanin mRNA was quantified by real-time PCR and peptide content was assayed by enzyme-linked immunosorbent assay. Galanin mRNA increased approximately 3-fold after MI in cardiac sympathetic neurons of both genotypes compared to unoperated and sham controls. Left ventricular galanin content, however, increased after MI only in Sprague-Dawley rats and not in AOGEN rats. These data suggest that post-infarct cardiac sympathetic hyperactivity stimulates galanin peptide production but is not required for increased galanin mRNA expression.     

Vagal modulation of responses elicited by stimulation of the aortic depressor nerve in neurons of the rostral ventrolateral medulla oblongata in the rat.

Stimulation of cervical vagal afferents inhibits central sympathetic outflows in part by inhibiting the ongoing activity of putative baroreceptive neurons in the rostral ventrolateral medulla oblongata. The aim of the present study was to examine the electrophysiological characteristics of vagal responses and their interactions with responses elicited by stimulation of the aortic nerve in neurons there. The study focused on the role of the long-lasting, late-onset vagal inhibition, which is likely to play an important role in the tonic inhibitory effects of vagal afferent stimulation. In vivo intracellular recordings were obtained from 33 neurons that received convergent inputs from aortic and vagal afferents. Sixty-four percent of these neurons exhibited a late inhibition following electrical stimulation of myelinated vagal afferents (mean onset latency of 100+/-5 ms). The average duration of late inhibition (294+/-19 ms) exceeded the duration of the cardiac cycle. As a consequence of this, sustained vagal stimulation diminished the effect of rhythmic baroreceptor inputs in neurons that exhibited late vagal inhibition. Simultaneous activation of aortic and vagal afferents significantly increased the magnitude of late inhibition, even in those neurons where stimulation of the aortic nerve alone did not elicit a response (n = 15). This suggested that the convergence between vagal and aortic afferent inputs occurred in inhibitory inteneurons antecedent to the recorded rostral ventrolateral medulla oblongata neurons. Focal stimulation of the caudal part of the nucleus of the solitary tract also elicited a late-onset inhibition in 73% of the neurons that responded to stimulation of the aortic nerve. This inhibition appeared to be similar to the late vagal inhibition, except for its shorter average onset latency (64+/-7 ms). Based on this observation, it is proposed that inhibitory inteneurons that mediate late inhibition to rostral ventrolateral medulla oblongata neurons may lie within the caudal part of the nucleus of the solitary tract. The present study established that activation of myelinated vagal afferents exerts a complex modulation over the ongoing and evoked activity of neurons that respond to stimulation of the aortic nerve. The complex interaction that occurs between aortic and vagal inputs in neurons of the rostral ventrolateral medulla may be implicated in long-term modulation of sympathetic outflows in response to changes in the activation of visceral receptors supplied by vagus afferents. The modulation elicited by late vagal inhibition may help to adjust cardiovascular outflows according to requirements set by the thoraco-abdominal visceral environment.     

Interaction between the hypothalamic defence reaction and cardiac ventricular receptor reflexes.

The interference with regard to the cardiovascular and gastric motility responses which follows stimulation of the hypothalamic defence area (D.A.) and a simultaneous afferent input from cardiac ventricular receptors was analysed in chloralose-anesthetized cats. In spinalized animals with only the vagal efferent innervation of autonomic effectors from supraspinal structures intact, a D.A. stimulation increased the heart rate to the same level irrespective whether the cardiac receptor afferents were stimulated or not. This suggests that the vagal component of the reflex bradycardia of cardiac receptor origin was completely suppressed by the D.A. stimulation. The reflex gastric relaxation to cardiac receptor activation, mediated via vagal efferent non-adrenergic fibres, was similarly completely blocked by D.A. stimulation. In contrast, the reflex inhibition of the sympathetic outflow to the heart and vessels from cardiac receptors was still effective during a D.A. stimulation, a phenomenon which seems compatible with a simple summation of excitatory D.A. and inhibitory cardiac receptor influences on the sympathetic neurons. The modifying influence from ventricular receptors on D.A. responses closely resembles that exerted by the arterial baroreceptors. The two reflex mechanisms thus work in concert and synergistically with the hypothalamic influences to produce maximal cardiac output and skeletal muscle perfusion without undue increases of pressure load on the pump during a defence reaction.     

A role for the paraventricular nucleus of the hypothalamus in the autonomic control of heart and kidney

It is now well accepted that the sympathetic nervous system responds to specific afferent stimuli in a unique non-uniform fashion. The means by which the brain transforms the signals from a single type of receptor into an appropriate differential sympathetic output is discussed in this brief review. The detection of and response to venous filling are used for illustration. An expansion of blood volume has been shown in a number of species to increase heart rate reflexly via sympathetic nerves and this effect is primarily an action of volume receptors at the venous-atrial junctions of the heart. Stimulation of these volume receptors also leads to an inhibition of renal sympathetic nerve activity. Thus the reflex response to an increase in plasma volume consists of a distinctive unique pattern of sympathetic activity to maintain fluid balance. This reflex is dependent on neurones in the paraventricular nucleus (PVN). Neurones in the PVN show early gene activation on stimulation of atrial receptors, and a similar differential pattern of cardiac sympathetic excitation and renal inhibition can be evoked by activating PVN neurones. Cardiac atrial afferents selectively cause a PVN GABA neurone-induced inhibition within the PVN of PVN spinally projecting vasopressin-containing neurones that project to renal sympathetic neurones. A lesion of these spinally projecting neurones abolishes the reflex. With regard to the cardiac sympathetics, there is a population of PVN spinally projecting neurones that selectively increase heart rate by the release of oxytocin, a peptide pathway that has no action on renal sympathetic outflow. In heart failure the atrial reflex becomes blunted, and evidence is emerging that there is a downregulation of nitric oxide synthesis and reduced GABA activity in the PVN. How this might give rise to increased sympathetic activity associated with heart failure is briefly discussed.     

Neural control of sympathetic nerve response to cardiogenic hypotension in anesthetized cat

The present study was designed to determine effect of the preganglionic splanchnic nerve activity (SNA) on the brief hypotension accompanied with the occlusion of left circumflex coronary artery (CxCAO) in chloralose anesthetized cats. Following CxCAO in animals with neuraxis intact, no significant alterations of SNA occurred despite the significant fall in mean blood pressure (MBP). A significant fall in MBP also occurred in vagotomized animals with arterial baroreceptors intact, but SNA was significantly augmented from 12.9 +/- 2.7 impulses/sec before CxCAO to 24.4 +/- 4.3 impulses/sec 60 sec after the occlusion. In vagotomized animals, in which their carotid sinuses were isolated and perfused with the constant pressure at a level equal to systemic blood pressure (112 +/- 6 mmHg) and with higher pressure (167 +/- 7 mmHg), SNA was not altered significantly during the hypotension due to CxCAO. When the carotid sinuses were perfused with lower pressure (53 +/- 8 mmHg), a significant increase in SNA occurred simultaneously with the decrease in MBP after CxCAO. The peak decreases in blood pressure during the coronary occlusion were significantly greater in the vagotomized group (-46 +/- 5 mmHg) and in the Low-CSP group (-50 +/- 5 mmHg) than in other groups. Onset of this excitatory efferent sympathetic response to the hypotension due to the coronary occlusion in the vagotomized and Low-CSP groups was delayed significantly despite a significant fall in arterial blood pressure. These results show that vagal afferents from the heart may play a role of inhibiting the sympathetic augmentation mediated by arterial baroreceptors during cardiogenic hypotension. An excessive activation of cardiac receptors with sympathetic afferents may be induced by the profound fall in blood pressure, resulting in further impairment of cardiac function due to progressive myocardial ischemia under the condition of high sympathetic tone activated by baroreceptor reflex.     

Distribution and morphology of sensory and autonomic fibres in the subendocardial plexus of the rat heart

Cardiac reflexes originating from sensory receptors in the heart ensure blood supply to vital tissues and organs in the face of constantly changing demands. Atrial volume receptors are mechanically sensitive vagal afferents which relay to the medulla and hypothalamus, affecting vasopressin release and renal sympathetic activity. To date, two anatomically distinct sensory endings have been identified which may subserve cardiac mechanosensation: end-nets and flower-spray endings. To map the distribution of atrial receptors in the subendocardial space, we have double-labelled rat right atrial whole mounts for neurofilament heavy chain (NFH) and synaptic vesicle protein 2 (SV2) and generated high-resolution maps of the rat subendocardial neural plexus at the cavo-atrial region. In order to elucidate the nature of these fibres, double labelling with synaptophysin (SYN) and either NFH, calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT) or tyrosine hydroxylase (TH) was performed. The findings show that subendocardial nerve nets are denser at the superior cavo-atrial junction than the mid-atrial region. Adluminal plexuses had the finest diameters and stained positively for synaptic vesicles (SV2 and SYN), CGRP and TH. These plexuses may represent sympathetic post-ganglionic fibres and/or sensory afferents. The latter are candidate substrates for type B volume receptors which are excited by stretch during atrial filling. Deeper nerve fibres appeared coarser and may be cholinergic (positive staining for ChAT). Flower-spray endings were never observed using immunohistochemistry but were delineated clearly with the intravital stain methylene blue. We suggest that differing nerve fibre structures form the basis by which atrial deformation and hence atrial filling is reflected to the brain.     

Atrial natriuretic factor — A new hormone affecting kidney function

Summary A family of biologically active peptides (atrial natriuretic factor — ANF) has recently been identified in mammalian heart atria. The peptides derive from a common 152 amino acid precursor and at least 1% of total messenger RNA activity is specific for the factor. When injected intravenously ANF is hypotensive and natriuretic. Data indicate that atrial natriuretic factor represents a newly discovered hormone involved in the regulation of blood pressure and volume. Cellular release of ANF does not require the activation of the adenylate cyclase system, but is associated with receptor-mediated activation of the cellular polyphosphoinositide mechanism. The natriuretic effect includes increased glomerular filtration rate and specific inhibition of normal sodium reabsorption from the medullary collecting duct. The mechanism of this transport inhibition is not yet known.