Opposite modulating effects of the hypothalamic region on cardiac reflexes of Gadus morhua cod and Rana temporaria frogs

The effects of hypothalamic stimulation on cardiac reflexes have been investigated in the cod Gadus morhua and frog Rana temporaria. Cardiac reflexes were elicited by electrical stimulation of the medullar vagal lobes in fishes and central end of cardiac vagal branch in frogs. During simultaneous or successive stimulation of the hypothalamic region and vagal structures, modulation of the reflexes was observed. Reflex bradycardia was either augmented or inhibited, indicating the corresponding pattern of hypothalamic influences. No correlation was found between the parameters of stimulation, reflex intensity, hypothalamic region and the pattern of modulating influences. The data obtained suggest the existence of opposite modulating influences of the hypotalamic region upon parasympathetic reflexes in the heart of fishes and frogs.     

Adrenergic responses of the cardiovascular system of the eel, Anguilla australis, in vivo

Heart output, arterial pressures, and heart rate were measured directly in conscious unrestrained eels (Anguilla australis) and responses to intra-arterial injection of adrenaline monitored. Adrenaline increased systemic vascular resistance, heart output, and cardiac stroke volume in all animals. In some cases small transient decreases in stroke volume and hence heart output were seen at the peak of the pressor response: These probably reflect a passive decrease in systolic emptying due to increased afterload on the heart. In most cases, adrenaline produced tachycardia; but two animals showed consistent and profound reflex bradycardia, which was accompanied by a concomitant increase in stroke volume such that heart output was maintained or increased slightly. The interaction of changes in heart output and systemic vascular resistance produced complex and variable changes in arterial pressure. There was no consistent pattern of changes in branchial vascular resistance. Atropine treatment in vivo revealed vagal cardio-inhibitory tone in some animals and always blocked the reflex bradycardia seen during adrenaline induced hypertension. In some animals, adrenaline injection after atropine pretreatment led to the establishment of cyclic changes in arterial pressure with a period of about 1 min (Mayer waves).     

Cardiogenic reflexes after immune injury of the heart

Afferent and efferent spike activity from the parasympathetic (vagus) and sympathetic cardiac nerves were recorded simultaneously with ECG, and indices of heart function were measured in acute experiments on anesthetized dogs, which allowed us to study the modifications of cardio-cardiac reflex influences after a local immune heart injury. After an injury nidus has been formed in the heart, cardiogenic depressor reflexes evoked by an intracoronary application of veratrine or bradykinin were considerably suppressed or even abolished, and afferent spike activity in the vagus cardiac nerves noticeably decreased. At the same time, both the facilitation of activity in sympathetic afferent fibers and pressor reflex effects were preserved after the heart injury. Different localization of vagus and sympathetic afferent structures in the heart and their specialized sensitivity to the biologically active substances are suggested as the factors determining the pattern of cardiogenic reflex influences after a heart injury.Neirofiziologiya/Neurophysiology, Vol. 27, No. 1, pp. 18–25, January–February, 1995.     

Hypothalamic influences on unit activity in the cat superior colliculus

Experiments on immobilized unanesthetized cats showed that hypothalamic stimulation effectively modified spontaneous unit activity and activity evoked by photic stimulation in the superior colliculus. Long-latency responses, often with a tonic type of formation, were predominant. Meanwhile, definite differences were found in the character of influences from different regions of the hypothalamus. Stimulation of the anterior hypothalamic region and lateral hypothalamus led more frequently to inhibition of spontaneous activity, often expressed as the development of initial inhibition, especially during stimulation of the lateral hypothalamus. Definite modulation of spontaneous activity of cyclic type also developed. Influences from these structures on activity evoked by photic stimulation were chiefly facilitatory and modulating in character. Stimulation of the ventromedial nucleus could produce inhibitory and facilitatory effects equally on activity of tectal neurons, with a tendency for the frequency of manifestation of facilitation to increase when a series of stimuli was used. The mechanisms of triggering and realization of hypothalamic influences on activity in the superior colliculus are discussed.Ivano-Frankovsk State Medical Institute, Ministry of Health of the Ukrainian SSR. Translated from Neirofiziologiya, Vol. 11, No. 6, pp. 560–568, November–December, 1979.     

Electrophysiological study of hypothalamic neurons and gonadotropin regulation in rhesus monkey (author's transl)]

The electrical activity of various hypothalamic areas was recorded in anesthetized (sodium pentobartital) (n = 3) and unanesthetized (n = 3) ovariectomized rhesus monkeys. The plasma gonadotropin levels of the animals during the recording sessions were obtained by a chronic cardiac catheter. 1. Sodium pentobarbital greatly affected the electrical activity of most hypothalamic neurons (84%). The mean spontaneous electrical unit activity of neurons in the unanesthetized animals (n = 30) was 1.5 spike/sec. This value decreased to 0.1 spike/sec in the anesthetized group (n = 30). However, a small number of hypothalamic neurons were insensitive to the anaesthetic. 2. The multiunit electrical activity recorded in the median eminence showed marked periodic increases, about 200 sec before LH was observed to rise in the plasma (10/12). This increased firing lasted about 10 min (Fig. 1A). 3. In a few cases (2/12), however, increased firing was not associated with LH release. Since, in this area, multiunit activity represents the summation of a large number of axon terminals, the release of a hypothalamic hormone other than Gn-RH is put foreward as a possible hypothesis. 4. Of 51 neurons recorded in various hypothalamic areas, 3 showed periodic increases of electrical unit activity which corresponded to a rise in plasma LH levels (Fig. 1 B). These neurons are located in the arcuate area. 5. These results are consistent with the hypothesis of a relation between the electrical activity of some hypothalamic neurons and the periodical LH discharges observed in the ovariectomized rhesus monkey.     

The effect of morphine and opiate receptor agonists on arterial pressure and the bioelectrical activity of the renal nerve during stimulation of the midbrain central gray substance

It has been demonstrated in experiments on unrestrained and unanesthetized curarized cats that periaqueductal gray matter stimulation produce sympathetic-activating action, raise arterial pressure and heart rate, but at the same time is not effective enough to suppress the nociceptive shifts of haemodynamic reactions. Opioid mechanisms of spinal cord plays an essential role in sympathetic-activating action of periaqueductal gray matter. It is suggested that the influence of antinociceptive areas of the brain stem on sympathetic haemodynamic regulation is one of the causes of resistance of nociceptive haemodynamic reactions to narcotic analgetics.     

Effect of the dry-cold season dormancy on the tonic and phasic neural control of heart rate in the toad, Bufo paracnemis

This work examined basal heart rate and autonomic cardiac tone as well as sympathetic cardiac reactivity to hypotension induced by systemic nitroprusside injection in dormant toads (dry-cold season), Bufo paracnemis, comparing the values with those of toads collected during the active months (hot-rainy season). Autonomic tone was calculated according to the method of Lin and Horwath ('72), which allows its evaluation as a percentage of intrinsic heart rate. Specimens were maintained in an outdoors terrarium except for the week preceding surgery, when they were transferred to indoor nonclimatized tanks. The heart rate of dormant toads (27.8 +/- 2.7 beats/min) was lower than that of active toads at rest (38.6 +/- 2. 3). Cholinergic tone was higher than adrenergic tone both in active (26.2% and 7.8%, respectively) and aestivated (19.5% and 4.8%, respectively) animals. Thus, cholinergic tone and adrenergic tone were both lower in dormant animals. The reflex tachycardia elicited by nitroprusside-induced hypotension was lower in aestivated toads (9.3 +/- 0.9 beats/min) when compared to active toads (19.9 +/- 1.0), indicating a reduced sympathetic reactivity. Nitroprusside-induced hypotensions were not different in the two groups. We conclude that at rest Bufo paracnemis heart is under the influence of a double cholinergic and adrenergic tone, and that both influences, as well as the reflex adrenergic reactivity to the unloading produced by nitroprusside-induced hypotension, are reduced in aestivated toads.     

Increased incidence of isoproterenol-induced ventricular fibrillation in aging rats

Prolonged beta-adrenergic stimulation obtained by subcutaneous injection of isoproterenol in unanesthetized, unrestrained rats elicited ventricular fibrillation in approximately 80% of animals at 10-12 months of age. Ventricular fibrillation failed to occur in 1-month-old rats and involved only 12% of rats at 2 months. Senescence appeared not to increase the frequency of ventricular fibrillation since a similar incidence was seen in rats at 10-12 and 19-21 months. In all instances, ventricular fibrillation was preceded by ECG changes consistent with acute subendocardial ischemia. To evaluate whether acute beta-adrenergic stimulation elicits comparable cardiovascular effects in animals of different age, a dose-response curve to intravenous injection of isoproterenol was performed in anesthetized rats. Changes in heart rate, systemic arterial pressure, left ventricular pressure, and dP/dt were not different among animal groups. It was concluded that the arrhythmogenic potential of isoproterenol may not be related to differences in cardiac beta-receptor sensitivity with age as suggested by the comparable changes in the inotropic and chronotropic actions of isoproterenol in the animal groups studied.     

Aspects of cardiovascular reflexes in pathologic states

Cardiovascular reflexes that are mediated by receptors in the heart and blood vessels control a variety of important hemodynamic and humoral functions. The action of these receptors can be shown to be abnormal in several pathologic states. Left atrial receptors exhibit a depressed discharge sensitivity in dogs with chronic congestive heart failure caused by an aortocaval fistula. The reflex effects of atrial receptor stimulation are also depressed in heart failure. Left ventricular receptor stimulation has been implicated in the abnormal vascular responses to exercise in patients with aortic stenosis. The arterial baroreflex control of heart rate is abnormal in animals and humans with various forms of hypertension. Arterial baroreceptors from hypertensive animals show a resetting of their pressure-discharge curve to higher pressures. The arterial baroreflex is also depressed in chronic heart failure. This effect may result from an abnormality of the efferent limb of the reflex arc or from changes in the interaction between baroreceptors and cardiac receptors centrally. A final possibility may be abnormal arterial baroreceptor discharge characteristics in heart failure.     

Daily form of rest in the catfish Ictalurus nebulosus and the frog Rana temporaria]

By means of recording the cardiac rhythm, respiration rate and motor activity in unrestrained animals, studies have been made on the dynamics of formation of cataleptic-like immobilization in the teleost I. nebulosus. Rhythmic illumination at a rate 3/min. (10 sec light on - 10 sec light off) in the daytime gradually caused the onset of immobilization in the fish. This immobilization is characterized by the specific heart rate, type of respiration and the degree of plastic tone. Under the same experimental conditions, the formation of photogenic catalepsy in the frog Rana temporaria was confirmed. Typical heart rate, respiration pattern and the degree of plastic tone were determined as well. The role of illumination rhythm in the onset of all conditions which are characteristic for the "awakefulness-rest" cycle is discussed.     

Corticotropin-releasing factor (CRF): mechanism to elevate mean arterial pressure and heart rate

The efferent mechanisms by which central administration of corticotropin-releasing factor (CRF) elevates mean arterial pressure and heart rate were assessed in unanesthetized, unrestrained rats. CRF increased blood pressure and heart rate by stimulating noradrenergic sympathetic nervous outflow. CRF-induced cardiovascular changes were not dependent on anterior pituitary hormone release, adrenomedullary epinephrine secretion, the renin-angiotensin system or circulating vasopressin.     

Mechanism of the effect of urethane on the secretion of prolactin in the male rat

A subcutaneous injection of urethane (200 mg/100 g body wt.) into adult male rats resulted in a significant increase in serum prolactin (PRL) at 30 minutes. Subsequent measurements at 60, 90 and 120 minutes postinjection revealed a marked and rapid decrease in serum PRL to levels significantly lower than those of unanesthetized animals. The administration of the dopamine antagonist pimozide (8, 40 or 200 μg) 30 minutes after urethane injection elevated serum PRL levels in a dose-dependent manner and thus prevented the urethane-induced depression in serum PRL observed at 60 minutes postinjection. Hypothalamic synthesis of ¹⁴C-dopamine from its precursor ¹⁴C-tyrosine was measured in both urethane-anesthetized and unanesthetized rats. The synthesis of hypothalamic dopamine was dramatically increased in the urethane-anesthetized animals as compared to newly synthesized hypothalamic dopamine levels in the unanesthetized controls. These results indicate that the PRL-inhibitory effects of urethane anesthesia in the rat may be exerted through increased dopaminergic activity.     

Neuronal activities related to thermoregulation

The hypothalamic thermoregulatory center was regarded as a black box some 20 years ago. Subsequent microelectrode exploration revealed the existence of two kinds of thermosensitive neurons in this area. Discharges of these neurons are now recorded not only from anesthetized animals but also from tissue explants, tissue slices, and unanesthetized animals as well. Neuronal responses produced by some stimuli have been compared to whole-body thermoregulatory responses. Parallelism between the two was found in the actions of chemicals, in integration of peripheral and central temperatures, in cortical influence, and in temperature effects on other hypothalamic functions, implicating specific key roles to thermosensitive neurons in thermoregulation.     

Modulation of the baroreceptor reflex by the dorsomedial hypothalamic nucleus and perifornical area

Neurons within the dorsomedial hypothalamic nucleus (DMH) and perifornical area (PeF), which lie within the classic hypothalamic defense area, subserve the cardiovascular response to psychological stress. Previous studies have shown that electrical stimulation of the hypothalamic defense area causes inhibition of the cardiac and (in some cases) sympathetic components of the baroreceptor reflex. In contrast, naturally evoked psychological stress does not appear to be associated with such inhibition. In this study, we tested the effect of specific activation of neurons within the DMH and PeF on the baroreflex control of renal sympathetic nerve activity and heart rate in urethane-anesthetized rats. Microinjection of bicuculline (a GABA(A) receptor antagonist) into the DMH caused dose-dependent increases in heart rate and renal sympathetic activity, shifted the baroreflex control of both variables to higher levels (i.e., increased the upper and lower plateaus of the baroreflex function curves, and increased the threshold, midpoint, and saturation levels of mean arterial pressure). The maximum gain of the sympathetic component of the baroreflex was also increased, while that of the cardiac component was not significantly changed. Increases in the midpoint were very similar in magnitude to the evoked increases in baseline mean arterial pressure. Microinjection of bicuculline into the PeF evoked very similar effects. The results indicate that disinhibition of neurons in the DMH/PeF region not only increases sympathetic vasomotor activity and heart rate but also resets the baroreceptor reflex such that it remains effective, without any decrease in sensitivity, over a higher operating range of arterial pressure.     

The effects of posture on blood pressure and heart rate in the three-toed sloth, Bradypus tridactylus

1. In unanesthetized, minimally restrained three-toed sloths, Bradypus tridactylus, the mean arterial pressure was 125/85 mmHg and the heart rate was 83.6 beats/min. There was no significant difference between these parameters whether the animal was erect or supine in the experimental chair. 2. Animals without any restraint had a mean blood pressure of 133/87 mmHg and a heart rate of 78.1 beats/min. There was no significant difference between these parameters whether the animal was seated or suspended from a horizontal bar and there was no significant difference between the minimally restrained and the unrestrained animals. 3. Tilting from the erect to the supine position produced large increases in blood pressure parameters, 37% in systolic and 21% in diastolic, reaching the maximum effect in a mean time of 38 sec. Tilting from the supine to the erect position caused even greater increases in pressure, 43% and 38% respectively, and reaching the maximum also in a mean time of 38 sec. 4. Tilting initially increased the heart rate, in going from erect to supine by 21% in 16 sec and from supine to erect by 23% in 20 sec. 5. In going from erect to supine there was a reflex bradycardia later, 15% below control level with a maximum at 40 sec, and to a lesser degree in going from supine to erect, 9% with maximum at 50 sec.     

Hemodynamic effects of calcitonin gene-related peptide in conscious rats

The cardiovascular effects of calcitonin gene-related peptide (CGRP) were examined in conscious, unrestrained rats. Changes in mean arterial pressure, heart rate and cardiac output were continuously monitored before and after i.v. bolus injection of CGRP (0.1-5 micrograms/kg). Injection of the peptide caused dose-dependent reductions in mean arterial pressure (-24 +/- 4 mmHg), which were accompanied by marked tachycardia. Cardiac output was significantly increased after CGRP but little change was observed in stroke volume. CGRP also reduced total peripheral resistance (-46 +/- 6%). These data indicate that the hypotensive actions of CGRP are mediated through peripheral vasodilation rather than through reductions in cardiac output. Pretreatment with propranolol significantly reduced the tachycardia responses to CGRP from 81 +/- 11 beats/min to 36 +/- 4 beats/min, but did not abolish the increase in heart rate. These data suggest that CGRP produces a tachycardia through reflex increases in cardiac sympathetic tone and through possible direct positive chronotropic effects on the heart.     

Effects of anesthetics on cardiovascular responses of the marmot Marmota flaviventris

The effects of pentobarbital (30 mg/kg), urethan (2 g/kg), chloralose/urethan (50 mg/kg, 500 mg/kg), and thiobutabarbital (Inactin, 100 mg/kg) on the mean arterial pressure (BP) and heart period (HP) of Marmota flaviventris were examined. Anesthesia significantly decreased BP by 22-27 mm Hg and HP by 123-151 msec. In a series of paired studies with eight marmots it was found that pentobarbital increased the BP response to phenylephrine and almost abolished the baroreflex HP responses to phenylephrine and nitroglycerin. In another series of animals right carotid occlusion in unanesthetized animals produced greater changes in BP and HP than occlusion of the left carotid. Chloralose/urethan, urethan, or Inactin reduced the reflex BP response to unilateral carotid occlusion by 50% and the HP response by 96%. It was concluded that the anesthetic agents investigated depress baroreflex responses significantly by influencing efferent sympathetic and parasympathetic reflex responses. They, therefore, are not appropriate for cardiovascular studies in acute, anesthetized preparations of the marmot and, perhaps, other hibernating species.     

Raphe nucleus and corticorophic activity in pigeons]

Multiple electrolytic lesions were placed in the raphe area of pigeons. Basal plasma corticosterone level (B) was found not to be altered. Stress-induced adrenocortical activation was markedly reduced in raphe lesioned pigeons as compared to controls. Electrical stimulation of the nucleus raphes in permanently implanted, unrestrained and unanesthetized birds induced a significant rise in B. However the magnitude of the response to raphe stimulating was lower (1/2 approximately) and especially later than after hypothalamic stimulation since it paralleled exactly the pattern of stress induced activation.     

Respiratory changes induced by prolonged laryngeal stimulation in awake piglets

To examine the role of the laryngeal reflex in modulating cardiorespiratory function, we stimulated the superior laryngeal nerves (SLN) bilaterally in unanesthetized, chronically instrumented piglets (n = 10, age 5-14 days). The SLN were placed in cuff electrodes and wires were exteriorized in the neck for stimulation. A cannula placed in the aorta was used for blood pressure recording and arterial blood sampling. During each experiment, 1-2 days after surgery, ventilation was recorded using whole-body plethysmography, and electroencephalogram and electrocardiogram were recorded after acute subcutaneous electrode placement. After base-line recordings, the SLN were electrically stimulated for 1 h. During this period, mean respiratory frequency decreased by 40-75% and apneas of 10-15 s were regularly interspersed between single breaths or clusters of breaths. Periods of breathing were always associated with opening of the eyes and generally with head and body movements, an awakening that occurred every 10-15 s. At 1 h into the stimulus period, minute ventilation had decreased by 57 +/- 7% (mean +/- SE), arterial partial pressure of O2 (PaO2) by 68 +/- 3 Torr, and arterial partial pressure of CO2 (PaCO2) had increased by 19 +/- 2 Torr. Throughout the entire stimulus period, mean blood pressure and average heart rate were maintained within 12% of base line. We suggest that: low-threshold SLN afferents exert primarily respiratory effects and only minor cardiovascular effects; breathing during laryngeal reflex activation is sustained by an arousal system; and the laryngeal reflex does not pose an imminent threat to the unanesthetized, awake, young animal.     

心力衰竭状态下的动脉压力感受器反射

心力衰竭是以心脏泵血功能降低（心输出量减少）为始动因素的临床综合征。心输出量降低首先引起动脉压力感受性反射失负荷,进而通过迷走-交感机制加快心率;同时,支配血管床的交感传出活动增强,进而增加总外周阻力。本文主要论述在心力衰竭状态下压力感受性反射在循环功能异常调控中的作用机制。本综述及我们近年的研究表明：（1）在心力衰竭状态下压力感受性反射功能明显减弱;（2）中枢血管紧张素Ⅱ和活性氧在压力感受性反射功能失调中发挥关键作用;（3）心交感传入刺激和化学感受性反射能抑制压力感受性反射;（4）适当的运动可以部分纠正异常的心血管反射活动。