Central opioid mechanisms and cardiovascular control in hemorrhagic hypotension.

Bleeding volume during standardized hemorrhagic hypotension was studied in anesthetized, artificially ventilated rats after specific stimulation or blockade of opiate receptor systems. Hypotension was produced by stepwise bleeding to 80, 60, and 40 mmHg systemic arterial pressure. Subcutaneous administration of morphine 15 min before the bleeding resulted in a decrease, whereas subcutaneous administration of naloxone resulted in a significant increase in the required bleeding volume. Intracerebroventricularly administered met-enkephalin, dynorphin, or specific antisera against these peptides caused no characteristic alterations of the bleeding volume although met-enkephalin and dynorphin caused a significant decrease at the 40 mmHg level. Bleeding volume, however, was markedly reduced when beta-endorphin was intracerebroventricularly administered and significantly elevated by intracerebroventricular administration of a diluted beta-endorphin antiserum. These data suggest that 1) opioid mechanisms are participating in the control of blood pressure and of bleeding volume during blood loss, 2) these control mechanisms might be activated centrally, and 3) beta-endorphin or a closely related peptide plays a major role in these control mechanisms.