© Cambridge University Press 2012. Homeostatic regulation of the cardiovascular system relies on the ability of the heart to recognize and respond to many extracellular signaling molecules, including peptides, biogenic amines, steroid hormones, fatty acid derivatives and a variety of other classes of small molecules (Table 8.1). These extracellular messengers reach their cellular targets by four different signaling routes: endocrine (carried in the bloodstream), neurotransmitter (released from nerve endings), paracrine (diffused from an adjacent cell), and autocrine (released by the same cell). The response to a given extracellular messenger (ligand, “first” messenger) is mediated by receptors, which are proteins that recognize and bind high-affinity specific ligands. After a ligand binds to a receptor, a multi-step signal transduction cascade is set in motion that eventually results in a functional response within the cell. This may be a change in intracellular ion concentration or gene expression, for example. However, the biological pathways that make up the signal transduction cascade generally branch at multiple steps, involve both positive and negative feedback loops, and often interconnect with other receptor signaling pathways to affect disparate pathways in a manner independent of the native ligand. This allows regulatory control to be exercised on signal transduction, which may take the form of amplification of the response, its integration with other responses, or its termination to prevent uncontrolled signaling after receptor binding. Such signal diversification explains how, during hemodynamic stress, neurohormonal-regulatory mediators (catecholamines, endothelin, angiotensin-II and vasopressin) may cause both short-term functional responses (positive inotropic, lusitropic, chronotropic effects, vasoconstriction and fluid retention), and also slower proliferative responses and programmed cell death (apoptosis), which play important (often maladaptive) roles in chronic heart disease.
Kiefer, T; Podgoreanu, MV
- Core Topics in Cardiac Anesthesia, Second Edition
Start / End Page
International Standard Book Number 13 (ISBN-13)
Digital Object Identifier (DOI)