Research reportRapid effects of corticosterone on cardiovascular neurons in the rostral ventrolateral medulla of rats
Introduction
Corticosteroid hormones are important circulating factors affecting a wide variety of body functions. It is generally believed that corticosteroids act via intracellular receptors that mediate slow genomic actions. However, many studies performed over the last two decades reported the occurrence of rapid steroid effects. For examples, corticosteroids applied locally or systematically led to very rapid changes in neuronal excitability of various brain regions 3, 9, 10, 21, 24, 28. The rapid effects of steroid hormones were not blocked by protein synthesis blockers [1]. Cortisol linked to bovine serum proteins, which was believed to be unable to penetrate the cytoplasmic membrane, was able to produce rapid hyperpolarisation in coelic ganglion cells from guinea pigs 4, 10. In consistence with the electrophysiological findings, neurochemical studies have demonstrated that corticosteroids could bind specifically to synaptic plasma membrane 19, 26and were able to modulate the binding characteristics of other neurotransmitter receptors 16, 17. The above observations have led to the postulation that steroid hormones can also effect non-genomically via putative membrane receptors 11, 18, 25. But the physiological significance of such non-genomic actions of corticosteroids still remains obscure. It therefore seems suitable to examine the rapid changes in the functions of different systems following acute application of corticosteroids. The primary goal of the present study was to investigate the rapid effects of a steroid hormone, corticosterone, on functionally identified brainstem cardiovascular neurons to understand the possible role of corticosteroids in rapid neural regulation of cardiovascular system.
Administration of a glucocorticoid into the cerebral ventricle led to slow and long-lasting decrease in blood pressure (BP), while administration of a mineralocorticoid led to an increase in BP [27]. The authors attributed the changes in BP to the classical genomic mode of actions of the steroids through intracellular receptors. Accordingly, mineralocorticoid receptors (MR or type I) and glucocorticoid receptors (GR or type II) were identified in various brain regions such as the hippocampus, hypothalamus and most brainstem monoaminergic nuclei 12, 22. Recently, however, Zhu et al. reported that corticosteroids microinjected into the rostral ventrolateral medulla (RVLM) resulted in very rapid increase in BP and heart rate 29, 30. These effects were probably due to non-genomic actions of the steroids through putative membrane receptors in the RVLM because of the rapidity of the responses. But microinjection study alone does not suffice to explain the mechanism of the pressor effects of the steroids in the RVLM due to limitations of microinjection technique. For example, the RVLM is anatomically and functionally heterogeneous and contains neurons that subserve a variety of functions such as cardiovascular regulation, descending modulation of nociception and control of respiration [13]. It was not possible to conclude from the microinjection study whether the haemodynamic changes were due to the direct effects of steroids on cardiovascular neurons or alternatively were secondary to changes in other functions such as respiration. The present study was therefore initiated to examine the rapid effects of corticosterone on firing rate of functionally identified cardiovascular neurons in the RVLM of the rat.
Section snippets
Surgery and general procedures
Experiments were performed on 60 adult male rats weighing between 280–430 g. The animals were anesthetized initially with an intraperitoneal injection of Nembutal (80 mg/kg). After cannulation of the trachea and the right femoral artery and vein, surgical anesthesia was maintained with intravenous injections of urethane (1.1 g/kg applied in three injections separated by 10 min). The animals were paralyzed with gallamine triethiodide (10 mg/kg initially and 4 mg/kg every 30 min, i.v.) and
Effects of iontophorized corticosterone on firing rate of RVLM neurons
In the first series of experiments, spontaneously active units were recorded from RVLM with four-barreled microelectrodes and were tested with iontophoretic application of corticosterone. A total of 116 units were tested. They all responded to DLH (excitation), which indicated that the recordings were made from cell bodies.
Of these 116 units, 52 fulfilled our criteria for cardiovascular neurons (Fig. 1). They fired irregularly with firing rates ranging from 5 to 26 spikes/s (13.8±0.8 spikes/s).
Discussion
The major findings of this study are two-folds. Firstly, iontophoretic application of corticosterone resulted in rapid changes in firing rate of cardiovascular and non-cardiovascular neurons of the RVLM. Importantly, corticosterone was also able to induce rapid excitation of bulbospinal pre-sympathetic neurons, which supports and extends the findings of Zhu et al. [29], that corticosteroids microinjected into the RVLM of the rat resulted in rapid increases in BP. The short onset latency and
Acknowledgements
This study was partly supported by a grant from Natural Science Foundation of China, No. 39330100. Thanks are due to Professor J. Lipski for critical discussions.
References (30)
- et al.
Voltage-clamp studies of the inhibition of γ-aminobutyric acid response by glucocorticoids in bullfrog primary afferent neurons
Brain Res.
(1987) - et al.
Actions of microiontophoretically applied glucocorticoid hormones on reticular formation neurons in the rat
Neurosci. Lett.
(1983) The subretrofacial vasomotor nucleus: anatomical, chemical and pharmacological properties, and role in cardiovascular regulation
Prog. Neurobiol.
(1994)Acute effects glucocorticoid on cat spinal motor neuron electrical properties
Brain Res.
(1982)- et al.
A comparative study of pre-sympathetic and Bötzinger neurons in the rostral ventrolateral medulla (RVLM) of the rat
Brain Res.
(1995) Antidromic activation of neurons as an analytic tool in the study of the central nervous system
J. Neurosci. Methods
(1981)- et al.
Glucocorticoids are modulators of GABAA receptors in brain
Brain Res.
(1985) - et al.
Effects of corticosterone on the electrophysiology of hippocampal CA1 pyramidal cells in vitro
Brain Res. Bull.
(1984) - et al.
Iontophoretic application of glucocorticoids inhibits identified neurons in the rat paraventricular nucleus
Brain Res.
(1988) - et al.
Steroid binding to synaptic plasma membrane: differential binding of glucocorticoids and gonadal steroids
J. Steroid Biochem.
(1983)
Corticosterone reduces the excitability of hippocampal pyramidal cells in vitro
Brain Res.
Effects of corticosterone on neurons of reticular formation in rats
Am. J. Physiol.
An electrophysiological study on the membrane receptor-mediated action of glucocorticoids in mammalian neurons
Neuroendocrinology
Functional organization of central pathways regulating the cardiovascular system
Physiol. Rev.
The activity of neurons in the rostral medulla of the rat during withdrawal from noxious heat
J. Neurosci.
Cited by (35)
Cortisol rapidly increases baroreflex sensitivity of heart rate control, but does not affect cardiac modulation of startle
2020, Physiology and BehaviorCitation Excerpt :Glucocorticoids promote constriction of peripheral blood vessels [20] and increase metabolism in cardiac muscle cells [21], which can both affect the neural feedback from cardiovascular interoceptors (e.g., arterial baroreceptors). Cortisol could also affect brainstem mechanisms that process afferent cardiac signals, such as the RVLM [22,23], and cortical structures, such as the ACC and the insular cortex [24–27]. While the effect of cortisol on cortical structures can be observed in vivo using neuroimaging techniques, the effect on brainstem structures requires an indirect approach, such as based on psychophysiological indicators.
Rapid corticosteroid actions on behavior: Mechanisms and implications
2009, Hormones, Brain and Behavior OnlinePlasma corticosterone levels is elevated in rats submitted to chronic intermittent hypoxia
2007, Autonomic Neuroscience: Basic and ClinicalInhibition of cortisol production with metyrapone prevents mental stress-induced endothelial dysfunction and baroreflex impairment
2005, Journal of the American College of CardiologyCitation Excerpt :A direct role for cortisol in mental stress-induced impairment of BRS has not previously been described in humans. Animal studies support the theory that glucocorticoids may act centrally to modify BRS, independent of any effect on blood pressure, and show that such actions are of rapid onset, being detectable within hours (30–32). The administration of cortisol to normal subjects, though it raises serum cortisol and produces hypertension after several days, has not consistently been shown to reduce BRS (33), and this suggests that in humans any negative influence of cortisol on BRS during the stress response may be acute and somewhat situation specific.
- 1
Now on temporary research leave to Autonomic Neuroscience Institute, Royal Free Hospital Medical School, Rowland Hill Street, London NW3 2PF, UK. Fax: +44-171-830-2949; E-mail: [email protected].