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Noradrenaline-induced smooth muscle relaxation in the specific region of canine facial vein: implications for facial and cranial circulation.

This study was performed to investigate the heterogeneity of physiological and pharmacological properties in segments of the facial veins with special reference to selective brain cooling. Canine facial veins were isolated and the isometric tension of each segment was measured using the organ bath technique. Vessels in the segments of the facial veins that run opposite to the buccal cavity automatically produced myogenic tone and tended to show spontaneous contractions, but vessels in other segments did not. When no contractile agent was used for precontraction, noradrenaline and adrenaline produced dose-dependent relaxations in the former venous segments, but contractions in the latter ones. A Schild plot analysis for metoprolol against denopamine and for ICI118,551 against salbutamol showed that the venous segments running opposite the buccal cavity contained both beta(1)- and beta(2)-adrenoceptors, but the other venous segments contained only beta(2)-adrenoceptors. Electrical field stimulation-induced tetrodotoxin-sensitive relaxations in the former venous segments were diminished by pretreatment with metoprolol, but not with ICI118,551, indicating that the electrical stimulation-induced relaxation may be related to the activation of beta(1)-adrenoceptors in the venous smooth muscles. In conclusion, the heterogeneity of the functional properties, especially in the distribution of beta-adrenoceptors, in different segments of canine facial veins was observed in the present study, and autoregulatory mechanisms, humoral mechanisms, and neural mechanisms were suggested to affect cranial venous drainage.

Adrenergic Agonists↗

Inositol 1,4,5-trisphosphate, inositide flux rates and pool sizes during smooth muscle relaxation.

Decreases in D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] content and changes in inositol phospholipid contents occurred during the time of atropine-induced relaxation of swine tracheal smooth muscle contracted with 55 microM carbachol. Decrease in Ins(1,4,5)P3 occurred in a pool which makes up 40% of the total content of this inositol phosphate and which has access to Ins(1,4,5)P3 5-phosphatase and/or 3-kinase. A 50% decrease in this pool occurred at 16 s after addition of atropine and within 6-10 s after inhibition of phospholipase C (PLC). The maximal fall in Ins(1,4,5)P3 occurred at a time when force had only decreased 30% of the maximal response. A phosphatidylinositol 4-phosphate (PIP) pool linked to muscarinic receptor-activation increased 160% after addition of atropine, the maximal response occurring at a time when relaxation was 80% complete. The mechanisms for this increase were the maintained formation of PIP and phosphatidylinositol 4,5-bisphosphate (PIP2) even though PIP2 hydrolysis was inhibited and the apparent chemical equilibrium between PIP and PIP2.

Animals↗

Colchicine alters apamin receptors, electrical activity, and skeletal muscle relaxation.

A low conductance calcium-activated K+ channel is thought to regulate the rate of firing of several excitable cells. In skeletal muscle the expression of this channel is under nerve control. Previously, we reported that axonal flow blockade of rat nerves, induced by colchicine, caused a transient increase in muscle apamin receptors, determined by 125I-apamin binding to membrane fractions. The increase in apamin receptors was correlated with repetitive discharges resembling myotonic potentials in the electromyogram, that were blockable by apamin. Here we show that the increase in muscle apamin receptors and the alteration of the electromyogram are followed closely by a slowing of the twitch relaxation, that in turn, is decreased by apamin. Furthermore, the presence of myotonic-like alterations in the electromyogram and a slowing of muscle relaxation when muscle apamin receptors are increased suggests that these channels may participate, among other factors, in the generation of some kinds of myotonia.

Animals↗

Propofol is superior to thiopental for intubation without muscle relaxants.

PURPOSE: To compare intubating conditions and cardiovascular changes following induction of anesthesia and tracheal intubation in patients receiving either lidocaine-remifentanil-propofol or lidocaine-remifentanil-thiopental prior to induction. METHODS: In a randomized, double-blind study 76 healthy adult patients were assigned to one of two groups: lidocaine 1.5 mg.kg(-1), remifentanil 2 mug.kg(-1) and propofol 2 mg.kg(-1) (Group P) or lidocaine 1.5 mg.kg(-1), remifentanil 2 mug.kg(-1) and thiopental 5 mg.kg(-1) (Group T). Ninety seconds after the administration of the hypnotic agent, laryngoscopy and tracheal intubation were attempted. Intubating conditions were assessed as excellent, good or poor on the basis of ease of ventilation, jaw relaxation, position of the vocal cords, and patient's response to intubation and slow inflation of the tracheal cuff. The mean arterial pressure (MAP) and heart rate (HR) were measured 45 sec after hypnotic agent administration, immediately after tracheal intubation, two and five minutes after intubation. RESULTS: Excellent intubating conditions were obtained in 84% of Group P patients and 50% of Group T patients (P < 0.05). The percentage decrease from baseline MAP was significantly higher in Group P than in Group T postinduction (27.4% +/- 11.6 vs 21.8% +/- 10.0) and immediately postintubation (19.0% +/- 16.7 vs 11.2% +/- 14.9). The percentage change from baseline HR was significantly higher in Group P than in Group T postinduction (13.8% +/- 9.7 vs 0.5% +/- 12.4), immediately postintubation (8.7% +/- 13.7 vs 2.1% +/- 13.1), and two minutes postintubation (7.04% +/- 14.3 vs 3.5% +/- 14.3). CONCLUSION: Lidocaine-remifentanil-propofol is superior to lidocaine-remifentanil-thiopental for tracheal intubation without muscle relaxants. However, it induces more hypotension and bradycardia.

Adolescent↗

Side effects of nondepolarizing muscle relaxants: relationship to their antinicotinic and antimuscarinic actions.

Since acetylcholine (ACh) is the 'master key' to different subtypes of nicotinic and muscarinic receptors, and muscle relaxants (MRs) available in clinical practice are structurally related to it, MRs may exert their unwanted effects through inhibition of these receptors. Since the subunit composition of nicotinic ACh receptors (nAChRs) of pre- and/or postsynaptic location and the binding potency of MRs to these and muscarinic receptors are different, a search for selective muscle nAChR antagonists without or with less side effects seems to be promising and important for clinical practice.

Animals↗

Effects of some centrally acting muscle relaxants on spinal root potentials: a comparative study.

The effects of intravenously administered mephenesin, tolperisone, baclofen, diazepam and midazolam on reflex activity were studied in unanesthetized spinal cats. Monosynaptic, as well as polysynaptic ventral root reflexes, the dorsal root potential and the dorsal root reflex were recorded simultaneously from L6-S1 segments. An analogue integrating method was developed for quantitative monitoring and recording ipsilateral spinal root potentials evoked by stimulation of the tibial nerve. Mephenesin (12.5-50 mg/kg) caused a significant and dose-dependent reduction in the polysynaptic and the dorsal root reflexes, slightly decreased the dorsal root potential but minimally affected the monosynaptic ventral root reflex. Tolperisone (2.5-10 mg/kg) dose-dependently inhibited both ventral root reflexes and the dorsal root reflex. It slightly prolonged the dorsal root potential without affecting the amplitude. Baclofen (0.5 mg/kg) abolished the monosynaptic reflex, partially inhibited the polysynaptic reflex, while dorsal root responses were less attenuated. Both benzodiazepines exerted similar actions, both qualitatively as well as quantitatively: the polysynaptic reflex was partially reduced while the monosynaptic reflex was not modified by diazepam or midazolam. Dorsal root responses were enhanced and the half-time of decay of the dorsal root potential was prolonged. Different patterns of action of muscle relaxants studied here are discussed in terms of their possible mechanisms of action. Profound depressant effects of mephenesin and tolperisone on the dorsal root reflex are in contrast to the small effect of both drugs on the dorsal root potential and might reflect their inhibition of spike-generating mechanisms. For a yet unknown reason, various spinal pathways are affected differentially by baclofen. In spinal cats, the reduction by benzodiazepines of the polysynaptic reflex may be related to the potentiation of some unidentified GABA-ergic inhibitory processes. The use of water-soluble midazolam, as a model compound instead of diazepam, is suggested because the usual organic solvents for diazepam may affect its action.

Animals↗