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Effect of halothane on myocardial cyclic AMP and cyclic GMP content of mice
Insights
Halothane anesthesia alters myocardial cyclic nucleotide levels in mice, decreasing cyclic AMP (cAMP) and increasing cyclic GMP (cGMP). Alpha-adrenergic antagonists partially block the cGMP increase, suggesting involvement of alpha adrenoceptors.
Area of Science:
- Pharmacology
- Cardiovascular Physiology
- Cellular Signaling
Background:
- Anesthetics can affect cellular signaling pathways.
- Cyclic nucleotides like cAMP and cGMP play crucial roles in cardiac function.
- The precise mechanisms by which halothane influences myocardial cyclic nucleotides are not fully understood.
Purpose of the Study:
- To investigate the effects of halothane on myocardial cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) content in mice.
- To explore the involvement of adrenergic receptors and muscarinic receptors in mediating these effects.
Main Methods:
- Mice were exposed to halothane anesthesia.
- Myocardial cAMP and cGMP levels were measured.
- The effects of atropine, prazosin, yohimbine, propranolol, and 6-hydroxydopamine on halothane-induced changes were assessed.
Main Results:
- Halothane caused a dose-dependent decrease in myocardial cAMP and an increase in cGMP.
- Alpha-adrenergic antagonists (prazosin, yohimbine) inhibited the halothane-induced cGMP increase but not the cAMP decrease.
- Propranolol reduced basal cAMP levels and blocked the halothane-induced decrease in cAMP.
- Atropine and 6-hydroxydopamine did not significantly alter the effects of halothane.
Conclusions:
- Halothane's effects on myocardial cyclic nucleotides are primarily peripheral and not mediated by muscarinic receptors.
- The increase in cGMP appears to involve alpha adrenoceptor mechanisms.
- The decrease in cAMP may result from inhibition of beta-adrenergic stimulation of adenylate cyclase.
Abstract:
Halothane, in anesthetic concentrations (0.6-1.8 volumes/100 ml), produced a dose-dependent decrease in myocardial cyclic AMP (cAMP) content and an increase in cyclic GMP (cGMP) content in mice exposed to a continuous flow of the anesthetic carried in air for 15 min. Atropine (up to 20 mg/kg i.p.) did not alter significantly the myocardial cyclic nucleotides content or the effect of halothane on cAMP and cGMP content. Prazosin and yohimbine had no significant effect on cAMP or cGMP content in the absence of halothane. Both alpha adrenergic antagonists inhibited the halothane-induced increase in cGMP content (ID50, 0.24 and 0.54 mumol/kg i.p. for prazosin and yohimbine, respectively). In contrast, the decrease in cAMP content induced by halothane was not altered by alpha adrenergic antagonists. Propranolol (2 mg/kg i.p.) diminished myocardial cAMP level and prevented the halothane effect on myocardial cAMP content. Pretreatment with 6-hydroxydopamine did not change the cGMP response to halothane. Thus, the action of halothane on myocardial cyclic nucleotides content appears to be predominantly a peripheral effect, not related to cellular mechanisms mediated by muscarinic receptors. The results suggest that the increase in cGMP content induced by halothane does not require intact adrenergic nerve endings and that cellular processes associated with the alpha adrenoceptor system may be involved; the decrease in cAMP content may be due to an inhibition of the beta stimulatory action of catecholamines on adenylate cyclase.