Naohito Terui

Effect of cardiac vagal and sympathetic nerve activity on heart rate in rhythmic fluctuations

Beat-to-beat changes observed in cardiac vagal and sympathetic nerve activity and their effects on cardiac cycle length were studied during slow wave blood pressure and heart rate fluctuations (third order rhythm) and during respiratory sinus arrhythmia. Recordings were made from both nerves simultaneously in chloralose anesthetized and artificially ventilated dogs. During slow wave fluctuations in heart rate, a linear relationship was found to exist between the number of spikes per pulse interval recorded from vagal and sympathetic nerves and the length of pulse intervals. During respiratory sinus arrhythmia the time course of rhythmic changes in nerve activity and in cardiac cycle length was analyzed. Comparison of time courses indicated that vagal discharges affected the timing of not the following beat, but the one after; while the sympathetic effect was further delayed, affecting the third beat after the discharge. Baroreceptor stimulation, which resulted in lengthening the cardiac cycle, shifted this relationship by one cycle, i.e. vagal discharges affecting the occurrence of the following beat, while sympathetic discharges affecting the beat after. These results provide evidence for the conclusion that in dogs both vagal and sympathetic nerve activity contribute to the control of cardiac cycle length, however, with different time relations and effectiveness.

Activity of barosensitive neurons in the caudal ventrolateral medulla that send axonal projections to the rostral ventrolateral medulla in rabbits.

In urethane-anesthetized rabbits, we successfully recorded unit activity of four neurons in the caudal ventrolateral medulla (CVLM) that were excited by orthodromic stimulation of the aortic nerve and by antidromic stimulation of the rostral ventrolateral medulla (RVLM). The sum of mean onset latency of excitation to stimulation of the aortic nerve (37.5 ms) and mean conduction time of antidromic spikes (10.5 ms) was close to the mean onset latency of inhibition of reticulospinal neurons in the RVLM to stimulation of the aortic nerve (47.1 ms) as previously reported by us. Three of 4 neurons received excitatory input from carotid sinus baroreceptors as well. Our results provide strong evidence for the hypothesis that neurons in the CVLM subserve the arterial baroreceptor-sympathetic vasomotor reflex.

The aortic nerve-sympathetic reflex in the rat

Abstract The effects of stimulation of aortic nerve A- and C-fibers on the renal and cardiac sympathetic nerve activities in anesthetized and immobilized Sprague-Dawley rats were investigated. A separate aortic nerve was found in 46 rats (90%) out of 51. Activation of A- and C-fiber groups, alone or in combination, resulted in an inhibition of renal and cardiac nerve activities. However, an excitatory component preceding the inhibitory component, representing the reflex response to stimulation of non-barosensory afferent fibers contained in the carotid sinus or aortic nerve, was never observed. This results provides electrophysiological evidence supporting the view that the rats aortic nerve does not contain a significant amount of functionally active non-barosensory afferents. As with the aortic nerve relfex in the rabbit and cat, the sympatho-inhibitory action of C-fibers was more powerful and longer-lasting than that of A-fibers. Furthermore, the C-fiber reflex was elicited at stimulus frequencies as low as 2 Hz. No significant difference was found between the reflex response of cardiac and renal nerves. On the other hand, stimulation of the superior laryngeal nerve, which constitutes an important pathway carrying arterial baroreceptor fibers, caused a reflex sympathetic response typically consisting of excitatory and inhibitory components. Thus, the rats aortic nerve provides a useful experimental means to activate selectively central neural structures associated with barosensory afferents and to elicit the reflex response homologous to that in the arterial baroreceptor reflex in rabbits and cats.

Leptin injection into white adipose tissue elevates renal sympathetic nerve activity dose-dependently through the afferent nerves pathway in rats

Recent studies suggested that leptin in white adipose tissue (WAT) affected the sympathetic out flow to several tissues. We examined whether elevations of renal sympathetic nerve activity (RSNA) and blood pressure (BP) could be observed by leptin injection into WAT in rats. Injections of leptin (10 and 100 ng/ml per kg) into WAT evoked the activation of RSNA dose-dependently. Circulating sympathetic nerve activators, such as leptin, insulin, glucose and lactate, were unchanged by any doses of leptin. In addition, BP was not affected by leptin injections during a 90 min experimental period. These data suggested that leptin activated the afferent nerves through the sensors in WAT, resulting in elevation of RSNA.

Neurons in the caudal ventrolateral medulla mediate the somato-sympathetic inhibitory reflex response via GABA receptors in the rostral ventrolateral medulla

In urethane-anesthetized rabbits, stimulation of the sural nerve, consisting of cutaneous afferents (A-fibers), evoked reflex responses consisting of an early small excitatory component followed by a prolonged inhibitory component in renal sympathetic nerve activity. Bilateral injections of GABA antagonist, bicuculline (4 nmol/site), into the rostral ventrolateral medulla (RVLM), where sympatho-excitatory reticulospinal neurons are located, attenuated the inhibitory component in a dose-dependent manner as well as the inhibition evoked by stimulation of the aortic nerve A-fibers (baroreceptor afferents). Bilateral injections of a neurotoxic agent, kainic acid (4 nmol/site, 3 sites/side), into the caudal ventrolateral medulla (CVLM), where sympatho-inhibitory neurons with axonal projection to the RVLM are located, diminished these sympatho-inhibitory responses. Therefore it is concluded that the sympatho-inhibition evoked by activation of somatic afferents was mediated by neurons in the CVLM and by GABA receptors in the RVLM, as was the sympatho-inhibition associated with the arterial baroreceptor reflex. Bilateral injections of kynurenic acid (4 nmol/site, 3 sites/side) into the CVLM did not affect the somato-sympathetic reflex response, but diminished the sympatho-inhibition produced by activation of the baroreceptor afferents. Sympatho-inhibitory neurons in the CVLM were activated by glutamate when baroreceptor afferents were activated, but another excitatory transmitter may participate in the somato-sympathetic reflex in the CVLM.

Direct measurement of renal sympathetic nervous activity in high-fat diet-related hypertensive rats.

The elevation of renal sympathetic nervous activity (SNA) is a possible cause of blood pressure (BP) elevation. Although a high-fat diet (FAT) often induces BP elevation in animals, the effect of FAT on renal SNA in animals is not consistent between studies. Thus, we compared the basal levels of efferent renal SNA and BP in FAT- or high-carbohydrate diet (CHO)-fed rats. Twenty-four male Sprague-Dawley rats were fed FAT (P/F/C=20/45/35% cal) or CHO (20/5/75) from 5 weeks of age. After 20-21 weeks of feeding, a 24-h urine sample was collected to measure sodium excretion. The next day, blood (0.2 ml) was withdrawn from a femoral artery, and basal efferent renal nerve discharges and mean arterial pressure (MAP) were recorded under anesthesia. Immediately after the experiment, abdominal (epididymal, perirenal and mesenteric) adipose tissues were dissected. Total abdominal fat weight was significantly greater in the FAT group than in the CHO group. The plasma level of leptin was significantly higher in the FAT group, but blood glucose and plasma insulin levels did not differ between the two groups. MAP and renal SNA were significantly higher in the FAT group. In addition, the ratio of urinary sodium excretion to dietary sodium intake was significantly lower in the FAT group than in the CHO group. The data suggest that the increased renal SNA may contribute to BP elevation in FAT-fed rats. The present study firstly demonstrated that renal SNA was elevated with FAT-related BP elevation.

Physiological and pharmalogical properties of the three subsystems constituting the aortic nerve-renal sympathetic reflex in rabbits

Electrical stimulation of the aortic nerve of anesthetized rabbits reflexly evoked both excitation and inhibition of renal nerve activity. The excitatory component of the reflex, observed in about 75% of the animals, was elicited by activation of aortic C-fibers. It was selectively suppressed by chronic treatment of the animal with capsaicin. Intracisternal injection of either [D-ala2]-met-enkephalinamide or beta-endorphin markedly attenuated this excitatory component, although neither affected the excitatory component mediated by chemoreceptor fibers in response to stimulation of the carotid sinus nerve. It seems most likely that nociceptive C-fibers of the rabbits aortic nerve were responsible for the excitatory component. On the other hand, the inhibitory component was reflexly elicited by stimulation of the aortic A- or C-fiber group activated separately or in combination. In agreement with previous reports, the sympatho-inhibitory action of C-fibers was more powerful and longer-lasting than that of A-fibers. We found that the inhibitory component induced by C-fibers was markedly attenuated by the two opioid peptides mentioned above, but was resistant to pentobarbital. On the contrary, the component mediated by A-fibers was suppressed by pentobarbital but was relatively resistant to the opioid peptides. Thus, the rabbits aortic nerve-renal sympathetic reflex consists of the following 3 subsystems characterized by different physiological and pharmacological properties: sympatho-inhibitory systems activated by barosensory A- or C-fibers and a sympatho-excitatory system attributable to C-fibers probably of nociceptive modality.

Changes in duodenal motility produced by noxious mechanical stimulation of the skin in rats

Three major pressure components were recorded in the duodenum of anesthetized rats by the balloon method: (1) small, fast, rhythmic waves which corresponded to the pendular movement of the duodenum; (2) large, slow, rhythmic waves which corresponded to the peristaltic movement; (3) the baseline component of the pressure. Noxious stimulation was applied to the skin of the neck, chest and abdomen, but only abdominal stimulation produced changes in duodenal pressure. The following three reflexes were observed whose efferent pathways were proven to be through sympathetic nerves and whose major pathway was apparently propriospinal: (1) a decrease in the amplitude of the small, fast, rhythmic waves; (2) a decrease in frequency of the large, slow, rhythmic waves; (3) a decrease in baseline of duodenal pressure.

Action of endothelin-1 on vasomotor neurons in rat rostral ventrolateral medulla

Intracisternal administration of endothelin-1 (ET-1) elicits sympathetically mediated cardiovascular responses by acting on the ventral surface of the medulla oblongata (VSM) subjacent to the rostral ventrolateral medulla (RVLM). We examined, in urethane-anesthetized rats, whether intracisternal ET-1 affected activity of vasomotor neurons (VMNs) in the RVLM, by acting either directly on the VMNs or indirectly via the VSM. VMNs were identified electrophysiologically. Intracisternal administration of ET-1 altered activity of all the 13 VMNs tested. At a dose of 0.1 pmol, ET-1 invariably caused transient excitation in six VMNs examined, whereas at a dose of 1 pmol in separate experiments all the seven VMNs tested were inhibited with (n = 6) or without (n = 1) preceding excitation. Similarly, topical application of ET-1 (0.1-1 pmol) to the VSM caused inhibition with (n = 3) or without (n = 2) preceding excitation in all the five VMNs tested. Direct iontophoretic application of ET-1 to the VMNs caused excitation in four of seven VMNs examined but did not affect the other three neurons. These results support the view that intracisternally administered ET-1 alters activity of VMNs in the RVLM, by acting directly on neurons themselves and indirectly via the VSM.

Rhythmic activities of the sympatho-excitatory neurons in the medulla of rabbits: neurons controlling cutaneous vasomotion

Spontaneous activities of the reticulospinal neurons in the reticular formation of the rostroventral medulla, of the ear sympathetic nerve (ESNA) and of the renal sympathetic nerve (RSNA) were analyzed with regard to cardiac cycle- and respiration-related rhythm in the anesthetized, vagotomized and immobilized rabbits. A reticulospinal neuron that was concurrently excited with increase in the ESNA and/or reduction of the blood flow of the ear skin by electrical stimulation of the dorsomedial hypothalamus was tentatively named as a cutaneous sympatho-excitatory neuron (Cu neuron). More than half of the Cu neurons (13/22) had a respiration-related rhythmic activity as well as the ESNA. Activity of most of the Cu neurons (19/22) was not modulated with the frequency of the heartbeat and the ESNA had little or no cardiac cycle-related activity. Simultaneous recording shows that the degree of modulation (relative power of the power spectrum of the post event time histogram at the frequency of the respiration) of activity of the Cu neurons correlated with that of the ESNA. On the other hand, most (13/18) of the barosensitive sympatho-excitatory reticulospinal neurons in the rostral ventrolateral medulla (RVLM neurons) had both cardiac cycle- and respiration-related activity as well as the RSNA had. The Cu neurons were located at the medial sites to the location of the RVLM neurons. These results further showed that the Cu neurons controlled the cutaneous vasoconstrictor fibers and that the sympatho-excitatory neurons were located at the different sites in the ventral medulla according to their function.