The diverse molecular mechanisms responsible for the actions of opioids on the cardiovascular system.

The actions of opioid agonist and antagonist drugs have not been well characterized in the heart and cardiovascular system. This stems from the limited role opioid receptors have been perceived to have in the regulation of the cardiovascular system. Instead, the focus of opioid receptor research, for many years, relates to the characterization of the actions of opioid drugs in analgesia associated with receptor activation in the CNS. However, recent studies suggest that opioid receptors have a role in the heart and cardiovascular system. While some of these actions may be mediated by activation of peripheral opioid receptors, others are not, and may result from direct or receptor-independent actions on cardiac tissue and the peripheral vascular system. This review will outline some of the diverse molecular mechanisms that may be responsible for the cardiovascular actions of opioids, and will characterize the role opioid receptors have in several cardiovascular pathophysiological disease states, including hypertension, heart failure, and ischaemic arrhythmogenesis. In many instances, it would appear that the effects of opioid agonists (and antagonists) in cardiovascular disease models may be mediated by opioid receptor-independent actions of these drugs.