Effects of long-term pretreatment with isoproterenol on inotropic responsiveness to alpha-adrenoceptor stimulation: study in isolated perfused rat hearts.
The effects of chronic pretreatment with isoproterenol (5 mg kg(-1)) daily for 10 days on cardiac alpha-adrenergic responsiveness in Langendorff heart preparations were investigated. Isoproterenol pretreatment caused cardiac hypertrophy (29%) as shown by a significant increase in the ratio of ventricular dry weight to body weight. In preparations from isoproterenol-pretreated rats, both maximum increases in left ventricular systolic pressure and heart rate elicited by isoproterenol (10(-12) to 10(-4) M) were significantly reduced (the isoproterenol concentration producing 50% of the maximum positive inotropic and chronotropic responses was enhanced almost 32- and 4-fold, respectively), while the positive inotropic response to phenylephrine (10(-12) to 10(-4) M) was significantly enhanced (the phenylephrine concentration producing 50% of the maximum positive inotropic effect was reduced almost 100-fold), compared with saline-pretreated rats. In preparations from both groups, phenylephrine infusion induced non-significant changes in heart rate and its positive inotropic response was reduced in the presence of propranolol (10(-7) M) in the perfusion medium. Even under beta-adrenoceptor blockade, the curve for the phenylephrine-induced positive inotropic effect remained shifted upward after isoproterenol pretreatment. Chronic isoproterenol pretreatment induces the expected cardiac beta-adrenoceptor desensitization while simultaneously enhancing the positive inotropic responsiveness to phenylephrine in Langendorff heart preparations. These findings support the hypothesis that cardiac alpha1-adrenoceptor stimulation may contribute to the maintenance of myocardial function under conditions in which beta-adrenoceptor function is compromised.
Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, PE, Brasil.
C O
CO
Silva
W O
WO
Monteiro-Filho
G P
GP
Duarte
S
S
Lahlou
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000473:pathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D011433:Propranolol; D007545:Isoproterenol