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Mechanism of cerebral blood flow autoregulation: Role of endogenous opioids
WS2-I-4-04 REGULATION OF SUPRA and INFRATENTORIAL CIRCULATION OF THE BRAIN BY BRAINSTEM NUCLEI H. Kim, K. Shimazu, T. Ohkubo, H. Sugimoto, Y. Asano, A.Onoda, Y. Nakazato, M. Sawada, D. Furuya and K. Hamaguchi Department of Neurology, Saitama Medical School, Saitama, Japan
[PURPOSE] Someofbrainstem nuclei send vasoactive fibers toboth supra and infratentorial cerebral vessels. The present study was aimed at elucidating the functional significances of these brainstem nuclei on the cerebrovasomotor responses tochanges in cerebral perfusion pressure. [MATERIAL&METHOD] Thirty-six monkeys (Macaca fuscata, 5.6+2.2kg, mean+S.D.) were stereotaxically operated and a bipolar electrode with 30/~ m tip was inserted to coagulate unilateral nucleus dorsalis nervi vagi, nucleus dorsalis raphes, nucleus centralis superior, or locus ceruleus. Internal carotid blood flow (ICBF) and vertebral blood flow (VBF) were continuously measured with electromagnetic flow probes with simultaneous recordings of blood pressure, heart rate and end-tidal PCO2. CBF autoregulation was quantatively analyzed by using the inde~ (A.I.= A ICBF(V BF)/Z~ MABP,ml/min/mmHg). [RESULTS] A) Carotid vascular system. 1) Induced hypotension : A.I. of the nucleus dorsalis raphes group significantly decreasedafter the lesion (p
WS2-I-4-05 MECHANISM OF CEREBRAL BLOOD FLOW AUTOREGULATION: ROLE OF ENDOGENOUS OPIOIDS KI Nagamachi ~, K. Shitara~, H. Morita1, H. Maeta ~-, S. Tanak~ H. Hosomi t 1) Department of Physiology, Kagawa Medical School, Kagawa, Japan 2) Department of Surgery, Kagawa Medical School, Kagawa, Japan To examine the role of the baroreceptors and the endogenous opioids in maintenance of cerebral blood flow (CBF), CBF was measured continuously using laser-Doppler flowmetry during changes in arterial pressure. Experiments were carried out adult mongrel dogs, anesthetized with pentobarbital sodium. A laser doppler flow probe (tip diameter of 0.3mm) was inserted into cerebral cortex through a hole of parietal bone for measuring CBF. The other laser doppler flow probe was put on temporal muscle for measuring muscle blood flow (MBF). Mean arterial pressure (MAP) was decreased or increased rampwise (+30 or +60 mmHg), by inflating a perivascular occluder around the inferior vena cava or by inflating a perivascular occluder around the descending aorta respectively. MBF decreased with decrease in MAP and increased with increase in MAP. On the other hand, CBF was well maintained despite changes in MAP. Thus, CBF showed a strong autoregulation. Carotid sinus denervation plus vagotomy did not show any significant effect on the MAP-CBF relationship. Baroreceptor reflex had no significant role in controlling of CBF during changes in MAP. However, the increase in MBF induced by the increase in MAP was significantly attenuated. Intravenous (2.5 mmol/kg) injection of naloxone, an opioid receptor antagonist, significantly attenuated the maintenance of CBF during changes in MAP. The effect of naloxone was more significant during the decrease in MAP compared with during the increase in MAP. On the other hand, intravenous injection of methyl naloxone (2.5 mmol/kg), which does not cross the blood-brain barrier, did not show any significant effect on the MAP-CBF relationship. Furthermore, intracerebroventricular injection of naloxone (2.5 nmol/kg) significantly attenuated the maintenance of CBF during the decrease in MAP. The effect was similar to that of intravenous injection of naloxone (2.5 mmol/kg). On the other hand, intravenous injection of naloxone with a small dose, which is the same dose as used in intracerebroventricular injection, did not show any significant effect on the MAP-CBF relationship. These findings suggest that endogenous opioids and central opioid receptors may be partly involve in the autoregulatory mechanisms of CBF. Especially, endogenous opioids may modulate cerebral vasodilation during the decrease in MAP.
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[PURPOSE] Someofbrainstem nuclei send vasoactive fibers toboth supra and infratentorial cerebral vessels. The present study was aimed at elucidating the functional significances of these brainstem nuclei on the cerebrovasomotor responses tochanges in cerebral perfusion pressure. [MATERIAL&METHOD] Thirty-six monkeys (Macaca fuscata, 5.6+2.2kg, mean+S.D.) were stereotaxically operated and a bipolar electrode with 30/~ m tip was inserted to coagulate unilateral nucleus dorsalis nervi vagi, nucleus dorsalis raphes, nucleus centralis superior, or locus ceruleus. Internal carotid blood flow (ICBF) and vertebral blood flow (VBF) were continuously measured with electromagnetic flow probes with simultaneous recordings of blood pressure, heart rate and end-tidal PCO2. CBF autoregulation was quantatively analyzed by using the inde~ (A.I.= A ICBF(V BF)/Z~ MABP,ml/min/mmHg). [RESULTS] A) Carotid vascular system. 1) Induced hypotension : A.I. of the nucleus dorsalis raphes group significantly decreasedafter the lesion (p
WS2-I-4-05 MECHANISM OF CEREBRAL BLOOD FLOW AUTOREGULATION: ROLE OF ENDOGENOUS OPIOIDS KI Nagamachi ~, K. Shitara~, H. Morita1, H. Maeta ~-, S. Tanak~ H. Hosomi t 1) Department of Physiology, Kagawa Medical School, Kagawa, Japan 2) Department of Surgery, Kagawa Medical School, Kagawa, Japan To examine the role of the baroreceptors and the endogenous opioids in maintenance of cerebral blood flow (CBF), CBF was measured continuously using laser-Doppler flowmetry during changes in arterial pressure. Experiments were carried out adult mongrel dogs, anesthetized with pentobarbital sodium. A laser doppler flow probe (tip diameter of 0.3mm) was inserted into cerebral cortex through a hole of parietal bone for measuring CBF. The other laser doppler flow probe was put on temporal muscle for measuring muscle blood flow (MBF). Mean arterial pressure (MAP) was decreased or increased rampwise (+30 or +60 mmHg), by inflating a perivascular occluder around the inferior vena cava or by inflating a perivascular occluder around the descending aorta respectively. MBF decreased with decrease in MAP and increased with increase in MAP. On the other hand, CBF was well maintained despite changes in MAP. Thus, CBF showed a strong autoregulation. Carotid sinus denervation plus vagotomy did not show any significant effect on the MAP-CBF relationship. Baroreceptor reflex had no significant role in controlling of CBF during changes in MAP. However, the increase in MBF induced by the increase in MAP was significantly attenuated. Intravenous (2.5 mmol/kg) injection of naloxone, an opioid receptor antagonist, significantly attenuated the maintenance of CBF during changes in MAP. The effect of naloxone was more significant during the decrease in MAP compared with during the increase in MAP. On the other hand, intravenous injection of methyl naloxone (2.5 mmol/kg), which does not cross the blood-brain barrier, did not show any significant effect on the MAP-CBF relationship. Furthermore, intracerebroventricular injection of naloxone (2.5 nmol/kg) significantly attenuated the maintenance of CBF during the decrease in MAP. The effect was similar to that of intravenous injection of naloxone (2.5 mmol/kg). On the other hand, intravenous injection of naloxone with a small dose, which is the same dose as used in intracerebroventricular injection, did not show any significant effect on the MAP-CBF relationship. These findings suggest that endogenous opioids and central opioid receptors may be partly involve in the autoregulatory mechanisms of CBF. Especially, endogenous opioids may modulate cerebral vasodilation during the decrease in MAP.
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