Influence of acetylcholine on the positive inotropic effect evoked by alpha- or beta-adrenoceptor stimulation in the rabbit heart
| Autor: | O.-E. Brodde, H.J. Schümann, J. Inui |
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| Rok vydání: | 1982 |
| Předmět: |
Inotrope
Male medicine.medical_specialty Stimulation In Vitro Techniques Isoprenaline Internal medicine Muscarinic acetylcholine receptor medicine Cyclic AMP Animals Pindolol Phenylephrine Cyclic GMP Pharmacology Chemistry Myocardium General Medicine Adrenergic beta-Agonists Papillary Muscles Myocardial Contraction Acetylcholine Stimulation Chemical Electrophysiology Endocrinology Female Sodium nitroprusside Rabbits Adrenergic alpha-Agonists medicine.drug |
| Zdroj: | Naunyn-Schmiedeberg's archives of pharmacology. 320(2) |
| ISSN: | 0028-1298 |
| Popis: | The influence of acetylcholine (ACh) on the positive inotropic responses to α- as well as β-adrenoceptor stimulation was investigated in the isolated electrically driven rabbit ventricular muscle. 1. Stimulation of muscarinic receptors by ACh (10−9–10−4 mol/l) reduced the positive inotropic effect evoked by isoprenaline (10−8 mol/l) via β-adrenoceptor stimulation, but enhanced the positive inotropic effect of the α-adrenoceptor stimulating agent phenylephrine (10−6 mol/l) in the presence of pindolol (3×10−8 mol/l). 2. Sodium nitroprusside (SNP) (10−6–10−3 mol/l) reduced the β-adrenoceptor-mediated positive inotropic effect but did not effect the α-adrenoceptor-mediated one. 3. The depression by ACh (10−6 mol/l) or SNP (10−4 mol/l) of the positive inotropic effects evoked by β-adrenoceptor stimulation was accompanied by a decrease of the cAMP level which has been elevated by isoprenaline. However, the enhancement of the α-adrenoceptor mediated positive inotropic effect by ACh seems to be independent of changes in cAMP- and/or cGMP-levels. 4. ACh (10−6 mol/l) diminished the shortening of the action potential duration induced by isoprenaline (10−8 mol/l) in Tyrode solution and Ca2+-dependent potential restored by β-adrenoceptor stimulation in 27 mmol/l K+ Tyrode solution. In contrast, ACh (10−6 mol/l) affected neither the prolongation of action potential duration nor the Ca2+-dependent potential caused by α-adrenoceptor stimulation. The depression by acetylcholine of the β-adrenoceptor mediated positive inotropic effect may be due to the decrease in cAMP content and to the reduction of the slow inward current while the enhancement by ACh of the α-adrenoceptor mediated positive inotropic effect is not associated with changes in cAMP- and/or cGMP-levels and in electrophysiological phenomena. It is concluded that the accentuated antagonism (Levy 1971) between sympathomimetic and parasympathomimetic agents at the postsynaptic region results mainly from the interaction between β-adrenoceptor- and muscarinic receptor-mediated responses, and that the α-adrenoceptor-mediated responses are able to counteract the accentuated antagonism. |
| Databáze: | OpenAIRE |
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