Attenuation by atenolol of myocardial acidosis during ischemia in dogs: contribution of beta-1 adrenoceptors to myocardial acidosis.
Coronary artery occlusion produces myocardial acidosis, which can be attenuated by propranolol or sotalol. The present study was undertaken to determine which beta adrenoceptors, beta-1 or beta-2, contribute to the ischemic myocardial acidosis. Dogs anesthetized with pentobarbital were used. In the first series of experiments, blood flow in the left anterior descending coronary artery was reduced by an occluder to about one-third of the original flow. Myocardial pH was measured by means of a micro pH electrode inserted into the left anterior descending coronary artery area at the depth of about 8 mm. The myocardial pH decreased from 7.44 to 7.55 to 6.73 to 6.89, 30 min after partial occlusion being the time immediately before an i.v. injection of drugs. Atenolol (1 mg/kg) attenuated significantly the decrease in myocardial pH that had been induced by partial occlusion, whereas IPS 339 (360 micrograms/kg) and ICI 118,551 (300 micrograms/kg) did not. The pH effect of atenolol was confirmed even in the paced heart. In the second series of experiments, the antagonistic action of these drugs on the isoproterenol-induced increase in heart rate and myocardial contractile force and the decrease in diastolic blood pressure was investigated. By this experiment, it was confirmed that atenolol has the beta-1 adrenoceptor antagonistic action, and the IPS 339 and ICI 118,551 have the beta-2 antagonistic action. These results suggest that the activation of beta-1 adrenoceptors contribute to the myocardial acidosis during ischemia.
Sakai
K
K
Abiko
Y
Y
D000138:Acidosis / Q000209:etiology / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism*; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008297:Male; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C026777:ICI 118551; D001262:Atenolol; C014898:IPS 339