Basal and Stimulated Sympathetic Responses After Epinephrine

Abstract

Abstract-Delayed facilitation of norepinephrine release through the action of epinephrine (NE) at presynaptic ␤-adrenoceptors has been postulated to account for the delayed hemodynamic effects of epinephrine and to be a mechanism causally related to the development of hypertension. To determine whether a short-term increase in epinephrine concentrations resulted in subsequent facilitation of sympathetic responses, 9 healthy subjects (age, 21Ϯ0.9 years) were studied at rest and during physiological stress on 2 occasions when they received an infusion of either saline or epinephrine (20 ng/kg per minute) in random order. Heart rate, blood pressure, forearm blood flow, epinephrine concentrations, and NE spillover were measured at rest, during mental stress (Stroop test), and during a cold pressor test. Measurements were performed before, during the 1-hour infusion of epinephrine or placebo, and 1 hour after the infusion. A radioisotope dilution method was used to measure NE spillover. Hemodynamic measurements and NE spillover were increased during the infusion of epinephrine, but 1 hour after discontinuation of epinephrine there was no significant augmentation of hemodynamic or sympathetic responses. NE spillover 1 hour after saline or epinephrine infusion was similar (0.85Ϯ0.2 versus 0.87Ϯ0.2 g/min; Pϭ0.92). In addition, there was no delayed facilitation of stress-induced hemodynamic or NE responses after epinephrine. These findings do not support the hypothesis that epinephrine results in delayed facilitation of NE release. (Hypertension. 1998;32:1016-1021.)Key Words: epinephrine Ⅲ norepinephrine Ⅲ sympathetic nervous system Ⅲ stress I t has been suggested that epinephrine plays a role in the pathogenesis of hypertension. [1][2][3][4] According to the "epinephrine hypothesis" of hypertension, epinephrine, released from the adrenal medulla during physiological stress, is taken up into sympathetic nerve terminals and later rereleased with norepinephrine (NE) as a cotransmitter. The epinephrine that has been rereleased stimulates further NE release through its action on presynaptic ␤-adrenergic receptors and in this way amplifies and prolongs sympathetic responses.1,4,5 Therefore, a brief increase in epinephrine concentrations, such as occurs in response to stress, could, through the mechanisms of uptake, rerelease, and stimulation of NE release, amplify and prolong sympathetic responses and facilitate the development of hypertension. 1,3,4 Experimental evidence supports the existence of functional presynaptic ␤-adrenergic receptors as well as the process of uptake and rerelease of epinephrine in the nerve terminal [5][6][7][8][9][10] : mechanisms that would allow epinephrine to produce a delayed and sustained facilitatory effect on NE release. Support for the physiological relevance of these mechanisms comes from studies that have demonstrated that short-term, systemic infusion of epinephrine resulted in prolonged tachycardic and/or pressor responses [11][12][13][14] and that low doses of epinephrine infused direct...

Determination of the Maximum Nonlethal Dose of Lidocaine and Epinephrine Based on Subcutaneous Injection in Rabbits

“…Although the injection of saline and epinephrine is frequently used in liposuction, few experimental studies were found in the literature. 15,16 The late deaths (after 48 hours) were not expected because we believed that epinephrine had a short-lasting action. 14 Our study conducted in rabbits demonstrates that a dose of 1.21mg/kg of body weight was safe when injected subcutaneously in the abdominal region.…”

“…3,12,13 All aspects of the changes caused by epinephrine in the human body have been widely published in the literature. 1,[14][15][16] Countless studies on the dose of epinephrine have considered only the intravenous administration. Because of its frequent use in surgery, particularly in plastic surgery, after the introduction of liposuction by Illouz in 1977 for the treatment of lipodystrophy and body contouring and because of the increase in the number of this type of surgery, there has been also a need to increase the dose of epinephrine in combination with the anesthetic substance for subcutaneous administration.…”