Epinephrine accounts for 80%, while norepinephrine accounts for 20% of the total hormone secreted from the adrenal medulla. Further, in certain situations epinephrine may be released as a co-transmitter with norepinephrine from postganglionic sympathetic nerves. Epinephrine is known as a prime mover in the “fight or flight” response with epinephrine elevating heart rate, augmenting neurogenic vasoconstriction, reducing blood flow to the skin and the kidneys, increasing the production of sweat, and widening the smaller bronchioles in the lungs. Its action raises blood-sugar levels by stimulating glucose production in the liver, and blood fatty-acid levels in adipose tissue. These effects on the cardiovascular system could perhaps play an important role in the onset and maintenance of hypertension, obesity and the metabolic syndrome (type 2 diabetes). The “epinephrine hypothesis” proposes that circulating epinephrine is taken up by sympathetic nerves, thereby promoting norepinephrine release during sympathetic nervous system stimulation. It is suggested that binding of co-released epinephrine to pre-synaptic β-adrenoceptors augments exocytotic release of norepinephrine and contribute to high blood pressure (hypertension). Thus, the “epinephrine hypothesis” might explain how the adreno-medullary hormonal system could contribute to the development of essential hypertension by augmenting sympathoneuroral norepinephrine release. There is evidence that the sympathetic nerves of hypertensive patients do release epinephrine as a co-transmitter. In this review, results will be presented which suggest that epinephrine is synthesized in situ in sympathetic nerve endings via the action of phenylethanolamine-N-methyltransferase (PNMT), which is induced by chronic mental stress exposure. Accordingly, this represents a biomarker of chronic mental stress, rather than a specific mechanism of hypertension, as proposed in the “epinephrine hypothesis”.
Keywords: Epinephrine, epinephrine hypothesis, hypertension, obesity, cardiovascular effect, sympathetic nervous system, catecholamine, body homeostasis, skeletal muscle, adipose tissue
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