Cardiovascular Effects of Endogenous Opiate Systems

Abstract

Opiates are among the oldest pharmacological substances known to man; their analgesic, euphoric, and addictive effects have been traditional focal points for opiate research. Without doubt, the cardiovascular effects of opiates have also been apparent to the user or abuser of opiate substances for several centuries. Persons seeking analgesic, euphoric, or antidiarrheal actions from opiate alkaloids have probably noted dizziness upon sudden st,anding due to the orthostatic hypotension these substances produce. His­ torically, however, scientific study on the cardiovascular responses to ad­ ministered opiates has lagged behind other areas of opiate research. This is understandable as, relative to doses required for their analgesic actions in humans, the cardiovascular effects of opiates are less noticeable and, indeed, undesirable. Early studies established that cardiovascular responses to morphine var­ ied among species; both autonomic and histamine-releasing properties con­ tributed to their hypotensive and bradycardic actions (1-5). Generally speaking, morphine was shown to produce prominent effects upon brain­ stem and hypothalamic centers that resulted in increased parasympathetic and decreased sympathetic tone (3-6). These effects upon autonomic out­ flow caused a depression of both heart rate and blood pressure. A resurgence of interest in opiate-cardiovascular interactions followed the discovery of endogenous opiate systems (for review see 7). A family of opioid peptides were found to be located at sites suggesting an autonomic action (8); also, opiate receptors were shown to be densely distributed in the brainstem and hypothalamus in close proximity to cardiovascular centers as well as endogenous opiate pathways (9, to). These anatomical findings