No evidence for involvement of endogenous opioid peptides in effects of clonidine on blood pressure, heart rate and plasma norepinephrine in anesthetized rats.

Endogenous opioid peptides have been implicated in the cardiovascular depressant actions of clonidine. The effects of clonidine have therefore been examined in anesthetized rats after pretreatment with naloxone, in morphine-dependent rats to determine if cross-tolerance operates and in hypophysectomized rats to determine whether circulating beta-endorphin may play a role. In normotensive and spontaneously hypertensive rats, naloxone (2 mg/kg i.v.) did not alter the blood pressure and heart rate response curves to successive doubling doses of clonidine (0.625-10 micrograms/kg i.v.). In normotensive and spontaneously hypertensive rats made morphine-dependent (3 X 75-mg morphine pellets s.c.), the cardiovascular responses to clonidine were not inhibited but rather enhanced with a greater maximal response of blood pressure and an increase in both the slope and the maximal response of the dose-heart rate response curve. Plasma clonidine levels were similar in normotensive and spontaneously hypertensive rats and corresponding morphine-dependent rats. In hypophysectomized rats, the effect of clonidine on blood pressure was also enhanced with an increase in the maximal response. The reduction in circulating norepinephrine concentrations produced by clonidine was similar in all groups. These results do not support a role for endogenous opioid peptides in the cardiovascular actions of clonidine but do suggest that factors in addition to a reduction in sympathetic nerve activity may be operating.