Possible Involvement of Cyclic Adenosine Monophosphate–independent Mechanism in the Positive Chronotropic Effect of Norepinephrine in the Isolated Guinea Pig Right Atrium
| Autor: | Mieko Asada, Masayuki Endou |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Chronotropic
medicine.medical_specialty Phosphodiesterase Inhibitors Guinea Pigs Cesium In Vitro Techniques Amrinone Norepinephrine (medication) Norepinephrine chemistry.chemical_compound Chlorides Heart Rate Internal medicine Cyclic AMP Animals Medicine Cyclic adenosine monophosphate Heart Atria Forskolin business.industry Colforsin Calcium Channel Blockers Adenosine Stimulation Chemical Anesthesiology and Pain Medicine Endocrinology Verapamil chemistry Catecholamine Milrinone business Adrenergic alpha-Agonists medicine.drug |
| Zdroj: | Anesthesiology. 95:437-444 |
| ISSN: | 0003-3022 |
| DOI: | 10.1097/00000542-200108000-00028 |
| Popis: | Background Although both positive chronotropic and inotropic effects of beta-adrenergic stimulation are thought to be mediated by cyclic adenosine 3'5'-monophosphate, phosphodiesterase III inhibitors such as amrinone and milrinone potentiate the positive inotropic effect of catecholamines with minimum influence on the heart rate in clinical setting. The aim of the current study was to compare the positive chronotropic effect of norepinephrine with that of forskolin to elucidate whether cyclic adenosine monophosphate is relevant to the chronotropic effect of norepinephrine. Methods Concentration-response curves for the positive chronotropic effects of norepinephrine and forskolin on the spontaneously beating right atria of guinea pigs were determined in the absence and presence of phosphodiesterase inhibitors or ion channel inhibitors. In some experiments, the left atria driven electrically were used to determine the positive inotropic effect of norepinephrine. Results Norepinephrine and forskolin increased the beating rate in a concentration-dependent manner. The positive chronotropic effect of forskolin was potentiated by amrinone and 3-isobutyl-1-methylxanthine, whereas the positive chronotropic effect of norepinephrine was not potentiated by the phosphodiesterase inhibitors. In contrast, the positive inotropic effect of norepinephrine was potentiated by amrinone. The hyperpolarization-activated inward current inhibitor cesium chloride and L-type voltage-dependent Ca2+ current inhibitor verapamil suppressed the chronotropic effect of norepinephrine, whereas these inhibitors did not affect the chronotropic effect of forskolin. Conclusion Norepinephrine increases the spontaneously beating rate by a different mechanism from that of forskolin, suggesting that cyclic adenosine monophosphate is causally unrelated to the positive chronotropic effect of norepinephrine in the guinea pig heart. |
| Databáze: | OpenAIRE |
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