Stimulation of carotid body chemoreceptors by saline saturated with 100% CO2 elicited an increase in mean arterial pressure, respiratory rate, tidal volume, and minute ventilation (VE). Microinjections of L-glutamate into a midline area 0.5-0.75 mm caudal and 0.3-0.5 mm deep with respect to the calamus scriptorius increased VE. Histological examination showed that the site was located in the commissural nucleus of the nucleus tractus solitarii (NTS). The presence of excitatory amino acid receptors [N-methyl-D-aspartic acid (NMDA); kainate, quisqualate/alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and trans 1-amino-cyclopentane-trans-1,3-dicarboxylic acid (ACPD)] in this area was demonstrated by microinjections of appropriate agonists. Simultaneous blockade of NMDA and non-NMDA receptors by combined injections of DL-2-aminophosphonoheptanoate (AP-7; 1 nmol) and 6,7-dinitro-quinoxaline-2,3-dione (DNQX; 1 nmol) abolished the responses to stimulation of carotid body on either side. Combined injections of AP-7 and DNQX did not produce a nonspecific depression of neurons because the responses to another agonist, carbachol, remained unaltered. Inhibition of the neurons in the aforementioned area with microinjections of muscimol (which hyperpolarizes neuronal cell bodies but not fibers of passage) also abolished the responses to subsequent carotid body stimulation on either side.(ABSTRACT TRUNCATED AT 250 WORDS)
Carotid and aortic chemoreceptor function was studied in normal Wistar rats. Sodium cyanide, lobeline HCl, and doxapram HCl in the doses of 2-400 mug/kg injected into the external carotid artery stimulated respiration significantly. Injections of the drugs into the ascending aorta produced less effects which were abolished after section of the carotid sinus nerves. The drugs produced a significant increase in the carotid sinus nerve activity but failed to do so in the aortic depressor or recurrent laryngeal nerves. These results indicate that the carotid chemoreceptor function in Wistar rats in normal while functional aortic chemoreceptors are absent in them.
The mechanism of cardiovascular responses to chemical stimulation of the hypothalamic arcuate nucleus (ARCN) was studied in urethane-anesthetized adult male Wistar rats. At the baseline mean arterial pressure (BLMAP) close to normal, ARCN stimulation elicited decreases in MAP and sympathetic nerve activity (SNA). The decreases in MAP elicited by ARCN stimulation were attenuated by either gamma-aminobutyric acid (GABA), neuropeptide Y (NPY), or beta-endorphin receptor blockade in the ipsilateral hypothalamic paraventricular nucleus (PVN). Combined blockade of GABA-A, NPY1 and opioid receptors in the ipsilateral PVN converted the decreases in MAP and SNA to increases in these variables. Conversion of inhibitory effects on the MAP and SNA to excitatory effects following ARCN stimulation was also observed when the BLMAP was decreased to below normal levels by an infusion of sodium nitroprusside. The pressor and tachycardic responses to ARCN stimulation at below normal BLMAP were attenuated by blockade of melanocortin 3/4 (MC3/4) receptors in the ipsilateral PVN. Unilateral blockade of GABA-A receptors in the ARCN increased the BLMAP and heart rate (HR) revealing tonic inhibition of the excitatory neurons in the ARCN. ARCN stimulation elicited tachycardia regardless of the level of BLMAP. ARCN neurons projecting to the PVN were immunoreactive for glutamic acid decarboxylase 67 (GAD67), NPY, and beta-endorphin. These results indicated that: 1) at normal BLMAP, decreases in MAP and SNA induced by ARCN stimulation were mediated via GABA-A, NPY1 and opioid receptors in the PVN, 2) lowering of BLMAP converted decreases in MAP following ARCN stimulation to increases in MAP, and 3) at below normal BLMAP, increases in MAP and HR induced by ARCN stimulation were mediated via MC3/4 receptors in the PVN. These results provide a base for future studies to explore the role of ARCN in cardiovascular diseases.
Abstract-Experiments were carried out in urethane-anesthetized, artificially ventilated, adult male Wistar rats. Microinjections (50 nL) of N-methyl-D-aspartic acid (1, 5, and 10 mmol/L), but not artificial cerebrospinal fluid, into the hypothalamic arcuate nucleus (ARCN) elicited increases in mean arterial pressure (5.7Ϯ0.5, 13.2Ϯ1.4, and 17.3Ϯ1.1 mm Hg, respectively) and heart rate (24.3Ϯ4. Key Words: blood pressure Ⅲ heart rate Ⅲ intrathecal injection Ⅲ microinjection Ⅲ N-methyl-D-aspartic acid Ⅲ sympathetic nerve activity T he hypothalamic arcuate nucleus (ARCN) is located bilaterally at the base of the third ventricle. Direct projections from the ARCN to the intermediolateral cell column of the spinal cord (IML), rostral ventrolateral medullary pressor area (RVLM), nucleus tractus solitarius, dorsal motor nucleus of the vagus, parabrachial nucleus, raphe nuclei, periaqueductal gray, and hypothalamic paraventricular nucleus (PVN) have been identified. 1-3 These reports suggest that the ARCN may be involved in the central regulation of cardiovascular function. There are very few studies in which the ARCN has been stimulated chemically to evaluate its role in cardiovascular or sympathetic nerve regulation. 4 -6 Therefore, a systematic study was carried out to investigate the cardiovascular effects of ARCN stimulation. Methods General ProceduresExperiments were done in adult male Wistar rats (Charles River Laboratories, Wilmington, MA) weighing 300 to 360 g (nϭ91). All of the animals were housed under controlled conditions with a 12:12-hour light-dark cycle. Food and water were available to the animals ad libitum. The experiments were performed according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and with the approval of the institutional animal care and use committee of the university.The general procedures have been described in detail elsewhere. 7 Briefly, the rats were anesthetized with urethane (1.2 to 1.4 g/kg; injected IV in divided doses). The absence of a pressor response and/or withdrawal of the limb in response to pinching of a hind paw indicated that the rats were properly anesthetized. The rats were artificially ventilated, and end-tidal CO 2 was maintained at 3.5% to 4.5%. Rectal temperature was maintained at 37.0Ϯ0.5°C. Blood pressure and heart rate (HR) were recorded by standard techniques. VagotomySilk sutures were placed loosely around the vagus nerves bilaterally for subsequent identification and sectioning of the nerves. Microinjections Into the ARCNDetails of microinjection procedure are mentioned elsewhere. 7 The coordinates for the ARCN were as follows: 3.6 to 3.8 mm caudal to the bregma, 0.1 to 0.2 mm lateral to the midline, and 9.8 to 10.2 mm deep from the dura. The same coordinates for the ARCN were used
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