Jan Jonason

Regulation of breathing in the rat: Indications for a role of central adenosine mechanisms

Abstract The adenosine agonist N 6 -phenylisopropyladenosite e (PIA) was given intracerebroventricularly to halothane-anesthetized rats. Administration of 10 μg PIA caused a decrease in pulmonary ventilation due to effects on both respiratory frequency as well as tidal volume. The respiratory depression was accompanied by bradycardia and hypotension. The data indicate that central adenosine mechanisms might be involved in respiratory and circulatory regulation.

Adenosine mechanisms in the regulation of breathing in the rat

The central respiratory effects of various adenosine (A) analogues were studied in halothane-anesthetized rats. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injections of the A analogues (2-Cla, L-PIA, CHA and NECA) reduced minute ventilation (VE) due to decreases in respiratory frequency (f) as well as tidal volume (VT). Dose-dependent effects were seen after i.c.v. L-PIA in both normal and vagotomized rats. Analysis of the A-induced changes using the occluded breath technique revealed an increase in expiratory time (TE) as well as a decrease in inspiratory drive. NECA, a relatively specific A2 agonist seemed to be somewhat more potent in eliciting respiratory depression than a relatively specific A1 agonist like L-PIA. Pretreatment with the methylxanthine theophylline completely antagonized the respiratory depression induced by L-PIA. It is concluded that central A receptors are involved in the central regulation of breathing and that A interacts with the respiratory control system mainly by decreasing inspiratory neural drive and prolonging expiratory time.

Central respiratory stimulant effect by thyrotropin in releasing hormone in the rat

Anaesthetized male rats were injected intracerebroventricularly with the tripeptide, thyrotropin releasing hormone (TRH). Respiratory frequency (f), tidal volume (VT) and minute volume (VE) were measured in a closed whole body plethysmograph by a low pressure transducer connected to a Grass polygraph. TRH induced an approximately 50% increase in f, while VT was not altered. VE increased in the same proportion as f. Our results indicate that TRH neurons or TRH-sensitive receptors may be involved in the regulation of central respiratory activity.

Evidence for a dopamine interaction with the central respiratory control system in the rat

Respiratory activity was studied in adult rats during light halothane anesthesia. Dopamine agonists and antagonists were injected intracerebroventricularly (i.c.v.) or systemically. The respiratory parameters were recorded after exposure to O2 or to CO2 in O2. Apomorphine (i.c.v. 300 microgram) induced a biphasic response with an initial decrease in respiratory frequency (f) followed by pronounced tachypnoea after 5 min. The changes in tidal volume (VT) showed an inverse pattern. When apomorphine was administered into the fourth ventricle, only the later phase of the biphasic response was observed. Haloperidol (2 mg/kg i.p.) antagonized the apomorphine-induced response in contrast to domperidone (2 mg/kg i.v.), a dopamine receptor blocking agent which does not pass the blood brain barrier. Administered i.c.v., haloperidol as well as domperidone induced a decrease in f while VT was increased. The same response was observed after the presynaptic dopamine receptor agonist 3-PPP, 3-(3-hydroxyphenyl)-N-n-propylpiperidine. Hypercapnea was found to decrease the tachypnea in apomorphine-treated animals. Apomorphine also induced a decrease in blood pressure and heart rate, which was not reversed by haloperidol. It is concluded that there is a centrally located, tonically activated dopamine system involved in respiratory regulation. The predominant effect seems to be of a respiratory stimulating nature. The possible role of presynaptic and different postsynaptic dopamine receptor mechanisms is discussed.

GABA-ergic mechanisms in central respiratory control in the anesthetized rat

SummaryRats lightly anesthetized with halothane were injected intracerebroventricularly (i.c.v.) with gamma-aminobutyric acid (GABA) and the GABA-like drugs, muscimol, baclofen and gamma-hydroxybutyric acid (GHBA). Respiratory frequency (f) was reduced after GABA (1 mg) but increased after baclofen (0.5 μg), while muscimol (0.5 μg) or GHBA (1 mg) did not affect f. However, GHBA administered repeatedly caused a dose-dependent increase in f.Tidal volume (VT) decreased in a dose-dependent fashion after i.c.v. administration of all the drugs used. Taken together, these changes in f and VT resulted mainly in a dose-dependent decrease in minute volume

DOPA-decarboxylase activity in sciatic nerves of the rat after constriction.

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Relative importance of neuronal and extraneuronal mechanisms for the uptake and retention of noradrenaline in different tissues of the rat

after GABA and muscimol while after baclofen and GHBA