The cardiovascular system is a highly complex, well organised system in which signal transduction plays critical physiological and pathophysiological roles. The cellular elements of the heart and vascular wall are equipped with an array of specific receptors and with complex intracellular machinery that facilitates and drives appropriate responses to extracellular stimuli. Understanding the mechanisms through which extracellular stimuli modify the functions of cells in the heart and vascular wall gives valuable insights into how perturbations of signalling systems can cause pathological situations. This knowledge will allow the identification of novel molecular targets for pharmacological intervention and will assist the future development of therapeutic strategies for managing cardiovascular disorders. This brief review will give a general overview of some major intracellular signalling systems operative in cells comprising the heart and vasculature, with particular emphasis on the pleiotropic roles of protein kinases as regulators of cell behaviour.

SENSING THE SIGNAL: THE ROLE OF G PROTEIN COUPLED RECEPTORS

Cells must be able to monitor and respond appropriately to changes in their extracellular environment, a process that is often termed “stimulus-response coupling”. Signal transduction (cell signalling) systems allow cells to detect changes in their extracellular milieu and to mount appropriate responses. Although numerous types of receptor systems have evolved to detect extracellular stimuli, the family of receptors that transmit signals through the activation of heterotrimeric GTP binding proteins (G proteins) are important in many different tissues and play prominent roles in cells and tissues of the cardiovascular system. These proteins represent the largest group of cell surface receptors encoded by the mammalian genome (> 1% of human genes), and in the cardiovascular system G protein coupled receptors (GPCRs) are implicated in more or less every regulatory event. Thus, signalling through GPCRs regulates the degree of peripheral arterial resistance, aspects of renal function, the rate and force of myocardial contraction, and cardiac hypertrophy.¹ GPCRs …