Role of endogenous opioids and central opioid receptors in cerebral cortical blood flow autoregulation.

Abstract

To examine the role of endogenous opioids in autoregulatory maintenance of cerebral cortical blood flow (CoBF), CoBF was measured continuously by laser-Doppler flowmetry during changes in arterial pressure. Experiments were conducted on pentobarbital sodium-anesthetized adult mongrel dogs. Mean arterial pressure (MAP) was decreased or increased by inflating a perivascular occluder placed around the inferior vena cava or the thoracic descending aorta, respectively. To exclude the influence of the baroreceptor reflex on the autoregulatory maintenance of CoBF, all experiments were conducted on dogs with bilateral carotid sinus denervation plus vagotomy. CoBF was well maintained within its normal range despite large changes in MAP. Intravenous injection of naloxone (2.5 mumol/kg), an opioid receptor antagonist, significantly impaired the autoregulatory maintenance of CoBF during the decrease in MAP. On the other hand, intravenous injection of methyl naloxone (2.5 mumol/kg), which does not cross the blood-brain barrier, did not exert any significant effect on the MAP-CoBF relationship. Furthermore, intracerebroventricular injection of a smaller dose of naloxone (2.5 nmol/kg) significantly impaired the autoregulatory maintenance of CoBF during the decrease in MAP, as the larger dose of intravenous naloxone (2.5 mumol/kg) did. On the other hand, intravenous injection of the smaller dose of naloxone did not exert any significant effect on the MAP-CoBF relationship. These findings suggest that endogenous opioids and central opioid receptors may be partly involved in the CoBF autoregulatory mechanism. The endogenous opioids may modulate the autoregulatory vasodilation of the cerebral cortex during the decrease in MAP.