Relationships Between the Release and Tissue Depletion of Norepinephrine from the Heart by Guanethidine and Reserpine

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Abstract
The release of norepinephrine from the heart of anesthetized open-chest dogs has been determined both after the intravenous administration of guanethidine (15 mg/kg) and after reserpine (3 mg/kg) by measuring the plasma norepinephrine concentration with the fluorometric method (THI) in bloods obtained simultaneously from the coronary sinus and femoral artery. In four dogs following the administration of guanethidine, norepinephrine release into the coronary sinus blood occurred and persisted for two to three hours. This release of norepinephrine was accompanied by and adrenergic response of similar duration. The norepinephrine content of atrial appendage was reduced by 24% of control at four hours in these dogs and to extremely low levels in three other dogs 24 hours after guanethidine administration. Thus, the reduction of the tissue content of norepinephrine continued after measurable release of norepinephrine into the coronary sinus blood had ceased. In four dogs following reserpine administration the adrenergic response was consistently smaller, and detectable release of norepinephrine into the coronary sinus blood was found transiently only in one dog. However, the norepinephrine content of atrial appendage was reduced by an average of 65% of control values at four hours. These findings suggest a difference in the mechanism of norepinephrine depletion in the period immediately after administration of guanethidine and reserpine.