On the mechanism of action of phenylephrine in rat atrial heart muscle.
Both in rat left atrial heart and in aortic smooth muscle preparations, phenylephrine (PE) caused a concentration-dependent increase in force of contraction (FC) in the presence of atenolol (10 mumol/l), which was antagonized by phentolamine, prazosin and WB 4101 in a competitive manner. The pA2 values of the antagonists in the cardiac tissue were 10-20fold lower than those in the rat thoracic aorta. In the spontaneously beating right atrium, PE exerted a positive chronotropic action, which was not significantly antagonized by phentolamine or prazosin. It is therefore assumed that the effects of phenylephrine in the left atrium and in the aorta are mediated by different subtypes of alpha 1-adrenoceptors, whereas the effects in the sino-atrial node are probably unrelated to alpha 1-adrenoceptors. To further elucidate the mechanisms of the positive inotropic effect of PE, action potential configuration and 45Ca2+ fluxes were monitored in the rat left atrium. The increase in FC by PE was associated with an increase in action potential duration (APD) and a reduction in resting membrane potential (RP). In the presence of (-)-devapamil (D888), the effects of PE on APD and RP persisted, whereas the increase in FC was antagonized in a non-competitive manner. Forskolin (300 nmol/l) enhanced the positive inotropic effect of PE. PE exerted a significant increase in 45CA2+ uptake in beating preparations, which was abolished in the presence of (-)D888 (1 mumol/l). In addition to the PE-induced increase in 45Ca2+ uptake, a decrease in 45Ca2+ efflux was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Jahnel
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U
Pharmakologisches Institut der Universität, Mainz, Germany.
Duwe
E
E
Pfennigsdorf
S
S
Nawrath
H
H
D008841:Actin Cytoskeleton / Q000187:drug effects; D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002132:Calcium Radioisotopes; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002132:Calcium Radioisotopes; D015221:Potassium Channels; D018340:Receptors, Adrenergic, alpha-1; D017923:Sodium-Hydrogen Exchangers; D010656:Phenylephrine; D002118:Calcium