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

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.

Role of the Autonomic Nervous System in the Circulatory Response to Acutely Induced Anemia in Unanesthetized Dogs *

“…It was therefore concluded that reflex slowing resulting from vagal stimulation or withdrawal of sympathetic activity had been eliminated; rather, the direct chronotropic effect of norepinephrine was observed (11). Finally, after the conclusion of this series of experiments, the right atrium was biopsied in seven of the eight dogs whose hearts had been denervated, and the norepinephrine concentrations were determined by the trihydroxyindole photofluorometric method, as detailed elsewhere (12). No …”

Correlation between the response of the heart to sympathetic stimulation and the release of endogenous catecholamines into the coronary sinus of the dog.

“…• The release of norepinephrine from the heart in response to direct stimulation of sympathetic nerves has been reported previously, but attempts to correlate the amount of endogenous neurotransmitter liberated with the intensity of physiological responses in vivo have been limited (1)(2)(3)(4)(5). For instance, an overflow of endogenous norepinephrine produced by a short period of stimulation has never been demonstrated at very low stimulation frequencies despite the fact that most innervated tissues respond physiologically to a frequency range of 1 to 3 Hz (6).…”

The effect of sustained stellate ganglion stimulation on left ventricular contractility in the dog.

“…Moreover, we observed that the effect of norepinephrine infusion on left ventricular dP/dt max did not differ after 60 min of left stellate ganglion stimulation (unpublished data). (Harrison et al 1963). These reduction rates are compatible with those seen in the present study.…”