Naohiro Koshiya

Ventrolateral medulla and sympathetic chemoreflex in the rat

Splanchnic sympathetic nerve discharge (SND), phrenic nerve activity (PND) and putative sympathetic premotor neurons of the rostral ventrolateral medulla (RVL) were recorded in urethane-anesthetized vagotomized rats without aortic baroreceptor afferents. Carotid chemoreceptor stimulation with brief N2 inhalation increased SND by 101 +/- 7%, raised mean arterial pressure (MAP) and increased the discharge rate of RVL premotor neurons by 46 +/- 12% (N = 32). During chemoreceptor activation. SND and most RVL neurons displayed pronounced central respiratory rhythmicity with maximal firing probability immediately after cessation of the PND (postinspiratory phase) and lowest probability during PND (inspiratory phase). Bilateral microinjection of the breed spectrum glutamate receptor antagonist kynurenic acid (Kyn, 5 nmol in 100 nl) into RVL blocked the sympathetic chemoreflex but left the sympathetic baroreflex intact. In contrast, bilateral microinjection of the same dose of Kyn into the caudal ventrolateral medulla (at obex level CVL) blocked the baroreflex but left the sympathetic chemoreflex intact. Bilateral microinjection of the GABAA agonist muscimol (87.5 pmol in 50 nl) into CVL produced effects identical to those of Kyn. These results confirm that the caudal ventrolateral medulla contains an essential relay of the sympathetic baroreflex and demonstrate that the same area plays no role in the sympathetic chemoreflex. The data suggests that these two reflexes could have a largely independent course through the medulla oblongata and that integration between the baroreceptor and chemoreceptor information used for sympathetic vasomotor control may occur as late as the premotor neuronal stage in RVL.

Chapter 8 Role of medulla oblongata in generation of sympathetic and vagal outflows

Publisher Summary This chapter reviews the present understanding of the medullary circuits that regulate the vasomotor sympathetic outflow and cardiovagal tone. It illustrates some of the recent progress in this area of integrative neurophysiology. Most concepts are based on the results of experimentation conducted under anesthesia but several components of the circuits have also been validated by neurophysiological work in unanesthetized preparations and by studies in behaving animals based on c-fos protooncogene expression. These medullary networks may be viewed from a reductionist perspective as embedded within a hierarchy of control systems that include higher centers involved in emotional behavior. Vast areas of uncertainty remain and competing theories are mentioned. A yet unknown fraction of spinal preganglionic neurons involved in vasomotor control may receive direct inputs from structures rostra1 to the medulla; however, individual components of the medullary circuits is described in this chapter are almost certainly recruited by supramedullary structures to generate the hemodynamic patterns characteristic of specific emotions.

WORKING MODEL OF THE SYMPATHETIC CHEMOREFLEX IN RATS

This review examines the neural network responsible for activation of the sympathetic vasomotor system during stimulation of carotid chemoreceptors (CC) in anesthetized vagotomized rats (sympathetic chemoreflex, SChR). Based on unit recording studies and experiments designed to impair synaptic transmission within selected lower brainstem nuclei or subregions, a model of the SChR is proposed with the essential features: i) key role of the nucleus of the solitary tract (NTS), rostral ventrolateral medulla (RVL) and ventrolateral pons (A5 area), ii) no role for caudal ventrolateral medulla (CVL), iii) modulatory role of dorsolateral pons and pre-Botzinger area, iv) dual control of bulbospinal presympathetic (preS) cells by CC inputs, one via the central respiratory network and the other through a direct excitatory pathway independent of the activity of this network, and v) independent medullary pathways for SChR and baroreflex until the preS neuronal stage in RVL.

Respiratory-Sympathetic Integration in the Medulla Oblongata

Homeostasis of tissue pO2 and pCO2 requires that pulmonary gas exchanges be matched by an adequate cardiac output and an appropriate distribution of the regional blood flows. This is achieved through the coordination of the various respiratory motor outputs (phrenic, intercostal, abdominal, laryngeal, pharyngeal, and bronchiomotor) with those governing vasomotion (sympathetic and cardiovagal). This chapter reviews some of the mechanisms responsible for the generation of a coordinated respiratory and sympathetic outflow. The related problem of how the cardiovagal parasympathetic output is matched to the respiratory activity will not be examined here (for reviews see Feldman and Ellenberger, 1988; Spyer and Gilbey, 1988; Richter and Spyer, 1990).

Central respiratory modulation of facial motoneurons in rats

Facial motoneurons (FMN) were recorded intracellularly in Sprague-Dawley rats anesthetized with halothane. The animals were vagotomized, paralyzed, and artificially ventilated. The average membrane potential of the cells was 62.6 +/- 1.9 mV and their input impedance ranged from 5 to 30 M omega (9.8 +/- 1.1 M omega, n = 38). The membrane potential of most FMNs varied throughout the central respiratory cycle and four distinct patterns were detected. Type I (post-inspiratory) cells (21/44) showed a two-phase Cl(-)-mediated hyperpolarization during the respiratory cycle, one during central inspiration and the second during late expiration. Type II cells (early inspiratory, n = 10) showed early inspiratory depolarization. Type III (n = 2, stage-2 expiratory) cells displayed late expiratory depolarization and one cell (type IV or throughout inspiratory) exhibited expiratory Cl(-)-mediated hyperpolarization. The remaining 10 cells showed no detectable respiratory modulation. The results reflect the heterogeneity of the central respiratory modulation of FMNs and suggest that these cells receive both excitatory and inhibitory inputs from elements of the central respiratory pattern generating network.

Sympatholytic effect of clonidine depends on the respiratory phase in rat splanchnic nerve

Peri-event averaging of the sympathetic nerve discharge was done to measure the magnitude of the sympatholytic effect of the anti-hypertensive drug clonidine during three different phases of the respiratory cycle (inspiration, I; postinspiration, post-I; late expiration, pre-I). Arterial pressure (AP) and discharges of splanchnic sympathetic (SND) and phrenic nerves (PND, onset used for peri-event averaging) were recorded in urethane-anesthetized, vagotomized, aortic deafferentated, paralyzed and artificially ventilated Sprague-Dawley rats (n = 7). During control periods (mean AP 106 +/- 10 mmHg) SND was distributed equally throughout the three selected respiratory periods, though two brief peaks were noted during the I and post-I periods. Low doses of clonidine (15-30 micrograms/kg i.v.) produced brief hypertension (< 30 s, 150 +/- 9 mmHg at peak) followed by moderate hypotension (89 +/- 3 mmHg) and a reduction in mean SND (-63 +/- 11% from control value). High doses of clonidine (200-250 micrograms/kg i.v.) produced sustained hypertension (> 10 min, 173 +/- 3 mmHg) and silence of SND. During this sustained hypertension, lowering AP by i.v. nitroprusside retrieved a component of SND that was barosensitive but insensitive to clonidine. During those hypotensive periods (spontaneous after a low dose of clonidine, and induced by nitroprusside after a high dose of clonidine), SND was most attenuated during the pre-I period and least during the I period. The I component of SND was significantly less attenuated than the post-I component by clonidine and, in most cases (6 out of 7), SND showed a single inspiratory peak following clonidine administration. It is concluded that (i) the pre-I component of SND is the most sensitive to clonidine and (ii) the I component of SND is the most resistant to the drug.