Alteration of norepinephrine responses in the dog by dual adrenergic blockade

Abstract

Norepinephrine was infused into anesthetized dogs at a rate of 10 μg/kg/min for 2 hr and the animals sacrificed after an additional 2 hr. Measurements were made in the presence and absences of alpha blockade (phenoxybenzamine, 7.5 mg/kg), beta blockade (propranolol, 2 mg/kg), and dual adrenergic blockade (phenoxybenzamine, 7.5 + propranolol, 2 mg/kg). At these dose levels beta blockade alone did not prevent the decrease in blood pH; the increase in hematocrit, serum potassium, serum phosphorus, and blood lactic aicd; or the production of pericardil effusion, cardiac hemorrhage, cardiac arrhythmias and ECG voltage depression. Alpha blockade alone blocked hematocrit, serum phosphoruus, pericardial effusion effects and deaths, and reversed the rise in serum potassium. Dual blockade was unique in eliminating cardiac arrhythmias, decrease in blood pH, changes in serum potassium, rise in blood lactate, and largely reducing blood pressure changes. These data support the concept that certain effects of catecholamines are mediated by a combination of alpha plus beta stimulation.