Fundamentals of receptor theory: basics for shock research

A variety of inflammatory mediators [e.g., tumor necrosis factor-alpha (TNF alpha)], endogenous hormones (e.g., epinephrine), and neurotransmitters (e.g., norepinephrine) are elevated as either a cause or a consequence of circulatory shock. The pathophysiologic responses observed during circulatory shock are the direct result of a complex interplay between the individual responses produced by the various mediators that interact with specific receptors. For example, as part of a compensatory response in circulatory shock, sympathetic outflow increases, which results in elevated synaptic levels of norepinephrine, which will activate alpha- and beta-adrenoceptors in the synaptic cleft. Additionally, plasma epinephrine and norepinephrine concentrations are elevated to a level sufficient to stimulate alpha- and beta-adrenoceptors in the heart, vasculature, and kidney, leading to profound changes in heart rate, cardiac output, peripheral vascular resistance, renal blood flow, and urine output. As such, the nature of the interaction between inflammatory mediators, hormones, and neurotransmitters with specific receptors in the cardiovascular system is fundamental to understanding the changes in circulatory status that occur during the shock state.