Cardiorespiratory responses to chemical activation of right ventricular receptors

Previous reports have shown that activation of left ventricular receptors with sympathetic afferents elicits increases in respiratory output and arterial pressure. The purpose of the present study was to determine whether similar responses are produced by chemical activation of epicardial receptors in the right ventricle. Receptors were stimulated by applying either capsaicin (10 micrograms) or bradykinin (500 ng) to the epicardial surface of the right ventricle in anesthetized cats. Application of either chemical evoked an increase in respiratory output (phrenic nerve activity), a decrease in heart rate, and a nonsignificant increase in arterial pressure in intact cats. However, capsaicin and bradykinin produced significant increases in arterial pressure, heart rate, and respiratory output after bilateral cervical vagotomy. In contrast, a fall in both heart rate and arterial pressure with only small increases in respiratory output were evoked after bilateral removal of the stellate ganglia in cats with intact vagi. Only small responses to the chemical stimulation of right ventricular receptors persisted after combined vagotomy and stellate ganglionectomy. These findings suggest that 1) activation of epicardial receptors with sympathetic afferents originating in the right ventricle causes an increase in cardiorespiratory function, and 2) activation of right ventricular receptors with vagal afferents produces decreases in heart rate and arterial pressure.     

Differential pattern of spinal sympathetic outflow in response to stimulation of the caudal medullary raphe

In urethan-anesthetized cats, frequency domain analysis was used to explore the mechanisms of differential responses of inferior cardiac (CN), vertebral (VN), and renal (RN) sympathetic nerves to electrical stimulation of a discrete region of the medullary raphe (0-2 mm caudal to the obex). Raphe stimulation in baroreceptor-denervated cats at frequencies (7-12 Hz) that entrained the 10-Hz rhythm in nerve activity decreased CN and RN activities but increased VN activity. The reductions in CN and RN discharges were associated with decreased low-frequency (相似文献   

Reaction of the hypothalamo-hypophyseal system of cats to stimulation of the cervical sympathetic nerve and the afferent fibers of the vagus nerve]

Data are presented on the functional morphology of the hypothalamo-hypophysial neurosecretory system of cats in stimulation of the cervical sympathetic nerve and of the afferent fibers of the vagus. Stimulation of the sympathetic nerve selectively activated the supraoptic nucleus and caused the discharge of the neurohormones from the posterior lobe of the hypophysis, whereas its infundibular portion contained much neurosecretory material. In response to the stimulation of the vagus all the portions of the neurohypophysis were released of the Gomori-positive substance; both the supraoptic and the paraventricular nucleus were activated.     

Sympathetic nerve and cardiovascular responses to chemical activation of the midbrain defense region

The changes in mean arterial pressure (MAP), renal (RBF) and femoral (FBF) blood flows, and inferior cardiac (CN) and vertebral nerve (VN) sympathetic nerve discharges (SND) produced by chemical activation (D,L-homocysteic acid) of the midbrain periaqueductal gray (PAG) were compared in baroreceptor-denervated and -innervated cats anesthetized with urethan. Defenselike cardiovascular responses in both states were similar in magnitude and consisted of increased MAP and FBF and decreased RBF; however, the nerve responses differed. In baroreceptor-denervated cats, PAG activation increased CN 10-Hz activity, decreased VN 10-Hz activity, and lengthened the CN-VN phase angle. In baroreceptor-innervated cats in which the rhythm in SND was cardiac related, PAG activation increased CN activity, but VN activity and the CN-VN phase angle were unchanged. These results demonstrate that chemical activation of PAG neurons induces differential patterns of sympathetic outflow generally consistent with accompanying defenselike cardiovascular responses. However, the mechanisms responsible for the changes in 10-Hz and cardiac-related SND appear to be different.     

Hypothalamic modulation of baroreceptor inhibition of the electrical activity in the renal nerve

Changes in the renal nerve sympathetic activity in response to electrical stimulation of posterior hypothalamus and vago-aortic nerve were studied in acute experiments on cats. It was shown that stimulation of certain points in hypothalamus defence area led to the suppression of baroreceptor reflex-mediated inhibition of the renal nerve sympathetic activity. Chloralosa depressed hypothalamic modulation of baroreceptor reflexes.     

Catecholamines abolish vagal but not acetylcholine tone in the intact cat trachea

To obtain evidence in the airways that catecholamines inhibit cholinergic neurotransmission, we recorded transverse tension in the posterior wall of an upper tracheal segment in anesthetized cats and compared the inhibitory effect of stimulating cervical sympathetic nerves when segment contraction was evoked by endogenous acetylcholine (vagal tone) with the effect when contraction was evoked by exogenous acetylcholine applied directly to the mucosal surface of the tracheal segment (ACh tone). We found that sympathetic stimulation abolished all contraction evoked by vagal tone but reduced ACh tone by only one-half. In a second group of cats we compared the inhibitory effects of sympathetic stimulation and intravenous isoproterenol during vagal and ACh tone and also during tone evoked by exogenous 5-hydroxytryptamine (5-HT tone). Sympathetic stimulation or isoproterenol injection abolished all vagal and 5-HT tone but again reduced ACh tone by only one-half. Our results suggest that catecholamines released from sympathetic nerves or injected into the circulation completely inhibit vagal tone. This inhibition may be partially responsible for inducing relaxation in airway smooth muscle.     

Interaction of histamine with noradrenergic constrictory mechanisms in cat cerebral arteries and veins

We examined responses of pial arteries and veins in situ to noradrenergic stimuli in the presence of histamine. Electrical stimulation of sympathetic nerves and perivascular microapplication of norepinephrine in mock cerebrospinal fluid produced constriction of arteries and veins in anesthetized cats. During simultaneous perivascular injection of histamine, these noradrenergic responses were attenuated or reversed. In both arteries and veins, constriction from sympathetic nerve stimulation was prevented by simultaneous application of the histamine receptor agonists, pyridylethylamine (H1) or impromidine (H2), results that suggest interference involving both types of histamine receptors. In arteries, impromidine, but not pyridylethylamine, inhibited constriction resulting from exogenous norepinephrine. Our findings indicate that histamine may have an inhibitory influence, exerted through both receptor types, on noradrenergic mechanisms in cerebral vessels.     

MLR stimulation and exercise pressor reflex activate different renal sympathetic fibers in decerebrate cats.

Although mesencephalic locomotor region (MLR) stimulation and the exercise pressor reflex have been shown to increase whole nerve renal sympathetic activity, it is not known whether these mechanisms converge onto the same population of renal sympathetic postganglionic efferents. In decerebrate cats, we examined the responses of single renal sympathetic postganglionic efferents to stimulation of the MLR and the exercise pressor reflex (i.e., static contraction of the triceps surae muscles). We found that, in most instances (24 of 28 fibers), either MLR stimulation or the muscle reflex, but not both, increased the discharge of renal postganglionic sympathetic efferents. In addition, we found that renal sympathetic efferents that responded to static contraction while the muscles were freely perfused responded more vigorously to static contraction during circulatory arrest. Moreover, stretch of the calcaneal (Achilles) tendon stimulated the same renal sympathetic efferents as did static contraction. These findings suggest that MLR stimulation and the exercise pressor reflex do not converge onto the same renal sympathetic postganglionic efferents.     

Mechanisms of the inhibitory effect of the stellate ganglion on cardiac activity

The mechanisms of cardiac activity inhibition caused by stimulation of the stellate ganglion were studied in acute experiments on 28 dogs and 37 cats and chronic experiments on 12 cats. It was shown that inhibition of cardiac activity is caused by stimulation of the parasympathetic fibers of the vagus, anastomozing with stellate ganglion branches and ingoing as part of these fibers to the heart. The hypothesis of change over of the sympathetic nerve fibers to the intracardial cholinergic neurons and the hypothesis of the cholinergic component in the mechanism of catecholamine release by the sympathetic nerve terminals was not confirmed. Therefore, the known Dale's principle as to that one neuron exerts its efferent effect with the aid of one transmitter is quite just. alpha-Adrenoreceptors does not produce any noticeable effect on cardiac activity.     

Defenselike patterns of spinal sympathetic outflow involving the 10-Hz and cardiac-related rhythms

Frequency- and time-domain analyses were used to compare the effects of stimulation of the defense region of the midbrain periaqueductal gray (PAG) on the 10-Hz and cardiac-related discharges of sympathetic nerves with different cardiovascular targets. In baroreceptor-denervated cats anesthetized with urethan, PAG stimulation at frequencies equal to or higher (up to 25 Hz) than that of the free-running 10-Hz rhythm produced an immediate and sustained decrease in vertebral sympathetic nerve (VN) 10-Hz activity but increased the 10-Hz discharges of the inferior cardiac (CN) and renal (RN) nerves. In baroreceptor-innervated cats, VN cardiac-related activity was initially unchanged by high-frequency (25-Hz) PAG stimulation, or it increased along with that in the CN and RN. Later, during high-frequency PAG stimulation, when the rise in blood pressure approached its peak, VN cardiac-related activity usually was reduced below control level. At this time, the increases in CN and RN cardiac-related discharges were largely sustained. The cardiac-related discharges of the three nerves were unaffected by PAG stimulation at frequencies just below or just above that of the heartbeat. We conclude that the defenselike pattern of spinal sympathetic outflow involving the 10-Hz rhythm is different in mechanism and character from that involving the cardiac-related rhythm.     

Absence of nonadrenergic noncholinergic relaxation in the cat cervical trachea

Published in vivo experiments have not supported in vitro reports of the presence of nonadrenergic noncholinergic (NANC) inhibitory pathways in the cat trachea. We therefore examined these pathways, measuring tension in an innervated tracheal segment, flow resistance in more distal airways, and dynamic compliance, in 10 anesthetized mechanically ventilated cats. Initially, cervical vagal stimulation evoked contraction followed by relaxation of smooth muscle of trachea and lower airways; sympathetic stimulation evoked relaxation only. After muscarinic blockade and restoration of smooth muscle tone with 5-hydroxytryptamine (5-HT) applied topically to the tracheal mucosa, vagal stimulation did not affect tracheal segment tension, whereas sympathetic-evoked relaxation was preserved. Similar results were found when tone was restored with intravenous 5-HT, with vagal stimulation also decreasing resistance and increasing compliance. We conclude that NANC pathways are present in lower airways but not in the cervical trachea of the cat. We hypothesize that parasympathetic constriction of cat airway smooth muscle can occur without simultaneous NANC activation, whereas NANC activity occurs only in tandem with parasympathetic stimulation.     

Cardiac sympathetic afferent stimulation augments the arterial chemoreceptor reflex in anesthetized rats.

Chronic heart failure (CHF) is well known to be associated with both an enhanced chemoreceptor reflex and an augmented cardiac "sympathetic afferent reflex" (CSAR). The augmentation of the CSAR may play an important role in the enhanced chemoreceptor reflex in the CHF state because the same central areas are involved in the sympathetic outputs of both reflexes. We determined whether chemical and electrical stimulation of the CSAR augments chemoreceptor reflex function in normal rats. Under anesthesia, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded. The chemoreceptor reflex was tested by unilateral intra-carotid artery bolus injection of potassium cyanide (KCN) and nicotine. We found that 1) left ventricular epicardial application of capsaicin increased the pressor responses and the RSNA responses to chemoreflex activation induced by both KCN and nicotine; 2) when the central end of the left cardiac sympathetic nerve was electrically stimulated, both the pressor and the RSNA responses to chemoreflex activation induced by KCN were increased; 3) pretreatment with intracerebroventricular injection of losartan (500 nmol) completely prevented the enhanced chemoreceptor reflex induced by electrical stimulation of the cardiac sympathetic nerve; and 4) bilateral microinjection of losartan (250 pmol) into the nucleus tractus solitarii (NTS) completely abolished the enhanced chemoreceptor reflex by epicardial application of capsaicin. These results suggest that both the chemical and electrical stimulation of the CSAR augments chemoreceptor reflex and that central ANG II, specially located in the NTS, plays a major role in these reflex interactions.     

Role of the medullary lateral tegmental field in reflex-mediated sympathoexcitation in cats

We tested the hypothesis that blockade of N-methyl-D-aspartate (NMDA) and non-NMDA receptors on medullary lateral tegmental field (LTF) neurons would reduce the sympathoexcitatory responses elicited by electrical stimulation of vagal, trigeminal, and sciatic afferents, posterior hypothalamus, and midbrain periaqueductal gray as well as by activation of arterial chemoreceptors with intravenous NaCN. Bilateral microinjection of a non-NMDA receptor antagonist into LTF of urethane-anesthetized cats significantly decreased vagal afferent-evoked excitatory responses in inferior cardiac and vertebral nerves to 29 +/- 8 and 24 +/- 6% of control (n = 7), respectively. Likewise, blockade of non-NMDA receptors significantly reduced chemoreceptor reflex-induced increases in inferior cardiac (from 210 +/- 22 to 129 +/- 13% of control; n = 4) and vertebral nerves (from 253 +/- 41 to 154 +/- 20% of control; n = 7) and mean arterial pressure (from 39 +/- 7 to 21 +/- 5 mmHg; n = 8). Microinjection of muscimol, but not an NMDA receptor antagonist, caused similar attenuation of these excitatory responses. Sympathoexcitatory responses to the other stimuli were not attenuated by microinjection of a non-NMDA receptor antagonist or muscimol into LTF. In fact, excitatory responses elicited by stimulation of trigeminal, and in some cases sciatic, afferents were enhanced. These data reveal two new roles for the LTF in control of sympathetic nerve activity in cats. One, LTF neurons are involved in mediating sympathoexcitation elicited by activation of vagal afferents and arterial chemoreceptors, primarily via activation of non-NMDA receptors. Two, non-NMDA receptor-mediated activation of other LTF neurons tonically suppresses transmission in trigeminal-sympathetic and sciatic-sympathetic reflex pathways.     

Peripheral and central mechanisms of the pressor response elicited by stimulation of the locus coeruleus in the rat

Electrical stimulation of the pontine nucleus locus coeruleus (LC) caused an increase of the arterial blood pressure in anesthetized rats, and elevated plasma noradrenaline (NA) and adrenaline (A) levels. The stimulation-induced pressor response was characteristically biphasic and consisted of a sharp rise in arterial pressure at the onset of the stimulation, followed by a second elevation at the end of the stimulus. Bilateral adrenalectomy or adrenal demedullation completely blocked the secondary phase of the pressor response elicited by stimulation, but did not affect the primary phase. The latter was specifically eliminated by the destruction of the peripheral sympathetic vasomotor axons with intravenous 6-hydroxydopamine (6-OHDA). The active sites eliciting the secondary adrenomedullary pressor component appeared to be restricted to the nucleus LC, whereas the primary sympathetic vasomotor response could be elicited from sites in and around the nucleus. After brain transection at the midbrain level, stimulation of LC failed to evoke the adrenomedullary pressor response, while the sympathetic vasomotor component was not affected. Similarly, destruction of brain NA neurons by intraventricular administration of 6-OHDA did not change the sympathetic vasomotor response, but virtually abolished the adrenal response. The results demonstrate that the pressor response to stimulation of LC in the rat is due to both increased sympathetic vasomotor activity and CA released from the adrenal medulla. The study also provides evidence suggesting that the noradrenergic LC cell group play an important role in the activation of the adrenal medulla, but is not essential for the activation of the sympathetic vasoconstrictor fiber system.     

Protein secretion from the cat parotid gland on nerve stimulation

1. The output and composition of proteins in nerve stimulated saliva samples were compared. 2. Protein output upon parasympathetic stimulation was higher than following sympathetic stimulation and was accompanied by an obvious degranulation of acini with the former but not the latter. These events are the converse of those in the rat parotid gland. 3. Superimposition of sympathetic upon parasympathetic stimulation caused an augmented output of salivary protein. 4. Electrophoresis of salivas revealed differences between individual cats in protein composition but not between differently stimulated salivas.     

Differential responses of regional sympathetic activity and blood flow to visceral afferent stimulation

The sympathetic nervous system is essential for the cardiovascular responses to stimulation of visceral afferents. It remains unclear how the reflex-evoked sympathetic output is distributed to different vascular beds to initiate the hemodynamic changes. In the present study, we examined changes in regional sympathetic nerve activity and blood flows in anesthetized cats. Cardiovascular reflexes were induced by either electrical stimulation of the right splanchnic nerve or application of 10 microg/ml of bradykinin to the gallbladder. Blood flows were measured using colored microspheres or the Transonic flow meter system. Sympathetic efferent activity was recorded from the left splanchnic, inferior cardiac, and tibial nerves. Stimulation of visceral afferents decreased significantly blood flows in the celiac (from 49 +/- 4 to 25 +/- 3 ml/min) and superior mesenteric (from 35 +/- 4 to 23 +/- 2 ml/min) arteries, and the vascular resistance in the splanchnic bed was profoundly increased. Consistently, stimulation of visceral afferents decreased tissue blood flows in the splanchnic organs. By contrast, activation of visceral afferents increased significantly blood flows in the coronary artery and portal vein but did not alter the vascular resistance of the femoral artery. Furthermore, stimulation of visceral afferents increased significantly sympathetic efferent activity in the splanchnic (182 +/- 44%) but not in the inferior cardiac and tibial nerves. Therefore, this study provides substantial new evidence that stimulation of abdominal visceral afferents differentially induces sympathetic outflow to the splanchnic vascular bed.     

Adenosine modulation of vasoconstrictor responses to stimulation of sympathetic nerves and norepinephrine infusion in the superior mesenteric artery of the cat

Vasoconstriction induced by sympathetic nerve stimulation and by norepinephrine infusion in the superior mesenteric artery of cats anesthetized with pentobarbital was inhibited by adenosine infusions in a dose-related way. The responses to nerve stimulation were not inhibited to a greater extent than the responses to norepinephrine, thus suggesting no presynaptic modulation of sympathetic nerves supplying the resistance vessels of the feline intestinal vascular bed. Blockade of adenosine receptors using 8-phenyltheophylline did not alter the degree of constriction induced by nerve stimulation or norepinephrine infusion, indicating that in the fasted cat, endogenous adenosine co-released or released subsequent to constriction does not affect the peak vasoconstriction reached. Isoproterenol caused similar degrees of vasodilation as adenosine but did not show significant antagonism of the pooled responses to nerve stimulation or norepinephrine infusion; there was no tendency for the degree of dilation induced by isoproterenol to correlate with the inhibition of constrictor responses. Thus, the effect of adenosine on nerve- and norepinephrine-induced constriction is not secondary to nonspecific vasodilation.     

Responses of neurons in the rostral ventrolateral medulla to whole body rotations: comparisons in decerebrate and conscious cats

The responses to vestibular stimulation of brain stem neurons that regulate sympathetic outflow and blood flow have been studied extensively in decerebrate preparations, but not in conscious animals. In the present study, we compared the responses of neurons in the rostral ventrolateral medulla (RVLM), a principal region of the brain stem involved in the regulation of blood pressure, to whole body rotations of conscious and decerebrate cats. In both preparations, RVLM neurons exhibited similar levels of spontaneous activity (median of ～17 spikes/s). The firing of about half of the RVLM neurons recorded in decerebrate cats was modulated by rotations; these cells were activated by vertical tilts in a variety of directions, with response characteristics suggesting that their labyrinthine inputs originated in otolith organs. The activity of over one-third of RVLM neurons in decerebrate animals was altered by stimulation of baroreceptors; RVLM units with and without baroreceptor signals had similar responses to rotations. In contrast, only 6% of RVLM neurons studied in conscious cats exhibited cardiac-related activity, and the firing of just 1% of the cells was modulated by rotations. These data suggest that the brain stem circuitry mediating vestibulosympathetic reflexes is highly sensitive to changes in body position in space but that the responses to vestibular stimuli of neurons in the pathway are suppressed by higher brain centers in conscious animals. The findings also raise the possibility that autonomic responses to a variety of inputs, including those from the inner ear, could be gated according to behavioral context and attenuated when they are not necessary.     

Nifedipine-induced inhibition of parasympathetic-mediated vasodilation in the orofacial areas of the cat

In anesthetized cats, we 1) compared the effects of antihypertensive agents (nifedipine, clonidine, phentolamine, propranolol, and nitroprusside) on the parasympathetic vasodilations elicited by lingual nerve (LN) stimulation in the lower lip and tongue and 2) investigated the mechanisms underlying the inhibitory effect of nifedipine on parasympathetic lower lip vasodilation. At the doses used, each antihypertensive agent reduced systemic arterial blood pressure by approximately 20 mmHg; however, the parasympathetic vasodilation elicited by LN stimulation was significantly reduced only by nifedipine. This inhibitory effect of nifedipine was not seen when LN was stimulated during ongoing repetitive stimulation of the superior cervical sympathetic trunk at 1-Hz frequency. This suggests that the ability of lip and tongue blood vessels to relax to parasympathetic stimulation is not directly impaired by this calcium channel blocker and that the inhibitory effects of nifedipine seen here probably resulted from an action on postsynaptic sites in vascular smooth muscle that caused a reduction in preexisting sympathetic vasoconstrictor tone (by inhibiting calcium influx into the vascular smooth muscle cell).     

Bioelectrical analysis of the regulatory interaction of sympathetic and parasympathetic nervous influences on the heart rhythm]

The changes of chronotropic effect on the isolated sinus node of the frog heart were studied during the separate and simultaneous stimulation of the sympathetic and intracardiac reflex parasympathetic pathways. Intracellular activity of the pacemaker cells was recorded. The separate stimulation of the intracardiac reflex system resulted in bradycardia (in winter) or tachycardia (in summer). Stimulation of sympathetic chain supervening the activation of the intracardiac pathways induced an intensification of both the parasympathetic bradycardia and tachycardia; these effects were cholinergic in nature. The recording of the intracellular pacemaker activity showed the existence of the complicated interaction between the sympathetic and parasympathetic pulse-mediator actions on the heart pacemaker both on the prepulase process and on the membrane polarization and other action potential parameters. Possible mechanisms of this interaction are discussed.