MORPHINE-INDUCED VENODILATION IN HUMANS

Morphine has been extensively used in the treatment of pulmonary edema , and its action is believed to be mediated in part by its ability to produce peripheral venodilation. This study investigated whether opiat es produce venodilation in human hand veins and explored the underlyin g mechanism(s). Fifteen healthy volunteers (11 men and four women) mer e studied with use of the dorsal hand vein compliance technique. After preconstriction with the selective alpha(1)-adrenergic receptor agoni st phenylephrine, dose-response curves were constructed to (1) opiate receptor agonists morphine (1 to 30 mu g/min) or fentanyl (0.07 to 1 m u g/min), (2) a combination of morphine and the mu-opiate receptor ant agonist naloxone, and (3) morphine and a combination of histamine (H-1 and H-2) receptor antagonists. Infusion of morphine caused venodilati on in a dose-dependent manner, whereas fentanyl did not produce venodi lation. Confusion of naloxone and morphine impaired the venodilation o nly slightly. Coinfusion of the H-1- and H-2-antagonists completely ab olished the venodilatory effect of morphine. These results suggest tha t the venodilatory effect of morphine is mediated through histamine re lease and that mu-opiate receptors have little or no involvement in th is process.