The cardiovascular actions of morphine and the endogenous opioid peptides.

T HE DISCOVERY, in 1973, of specific opiate receptors in the brain and, later, in the pituitary, sympathetic ganglia, kidney, liver, gastrointestinal tract, and heart suggested that there were endogenous substances that interacted specifically with these receptors.“’ Subsequently, a series of compounds that exhibited specific binding to these receptors were isolated from different tissues, including the brain, and were named enkephalins and endorphins or “endogenous opioids.“” I9 The first two such compounds to be discovered were the pentapeptides, methionine enkephalin (metenkephalin) and leutine enkephalin (leuenkephalin), differing only in a single amino acid, methionine or leucine.‘2,‘3 Shortly thereafter, the potent endogenous opioid, beta-endorphin, was isolated from the pituitary gland and was shown to be a polypeptide of 31 amino acids.“-*’ Beta-endorphin is derived from a 31,000 molecular weight glycoprotein, pro-opiocortin, found in the pituitary. This molecule contains not only beta-endorphin, but also adrenocorticotrophic hormone (ACTH) and enkephalins (Fig l).“-” This explains why ACTH and betaendorphin are found in the same cells of the anterior pituitary gland and why they are released in response to similar stimuli.‘8m37 Although the five N-terminal amino acids of beta-endorphin are identical with metenkephalin, suggesting that metenkephalin is derived from beta-endorphin, the amounts of the two compounds in various locations of rat brain and pituitary differ, suggesting that metenkephalin may also originate independently of beta-endorphin.” It has been suggested that growth hormone and metenkephalin or leuenkephalin may share a common precursor.3g Beta-endorphin, like morphine, possesses strong analgesic activity”-*’ and since the morphine antagonist naloxone can increase pain, it appears that release of beta-endorphin and/or other endogenous opioids may modulate the perception of pain.4M5 It also is clear that endogenous opioids have other physiologic properties. For example, they can affect respiration, vasopressin release, and free water clearance by the kidney.46mh5 Recently, they have been shown to have important cardiovascular actions and have been implicated in the pathogenesis of endotoxic or hemorrhagic shock, as well as hypertension. In this review, we will outline the distribution of opiate receptors and describe the actions of the principal endogenous opioids. Next, the cardiovascular effects of morphine, beta-endorphin, and the enkephalins will be discussed and contrasted. Finally, the possible roles of the endogenous opioids in the pathogenesis of circulatory shock and hypertension will be discussed.