Norepinephrine (NE) is an endogenous catecholamine and a direct acting adrenergic agonist. It is synthesized from dopamine by dopamine-beta-hydroxylase. NE is the body’s primary adrenergic neurotransmitter. It’s effects are mediated primarily through interaction at α-1 and β-1 receptors. It also has α-2 activity, though this primarily serves as a negative feedback system. NE is notable for its low degree of β-2 effects.
In clinical practice, NE is used for its cardiovascular effects. NE’s pharmacologic activity is exerted primarily through direct α-1 stimulation. Stimulation of the arterial α-1 receptors produces intense vasoconstriction and a resultant marked increase in systemic vascular resistance (SVR) and mean arterial pressure (MAP). Stimulation of venous α-1 receptors results in venoconstriction and increased venous return to the heart. NE also acts on β-1 receptors in the myocardium, resulting in a mild increase in myocardial contractility and myocardial oxygen requirements. However, NE has minimal effect on cardiac output and heart rate as the increase in afterload from α-1 stimulation results in a reflex bradycardia. While NE normally produces only mild increases in cardiac output, it should be noted that this in contrast to effect of a pure α-1 agonist such as phenylephrine, which typically decreases cardiac output.
NE α- 1 stimulation also results in decreased renal, mesenteric, and peripheral blood flow. These deleterious effects along with increased myocardial oxygen consumption can limit the usefulness of NE in treatment of refractory shock.