Rabkin S W
University of British Columbia, Vancouver, Canada.
Life Sci. 1994;54(22):1649-57. doi: 10.1016/0024-3205(94)00605-9.
The purpose of this study was to examine the roles of brain opioid receptors, using the opioid receptor antagonist naloxone, and brain alpha 2 adrenergic and imidazole receptors, using their agonist clonidine, in the hypertension and tachycardia induced by electrical stimulation of the AHA and PHA area. Unanesthetized and unrestrained Wistar rats 300-400 g that had previously had catheters inserted into the lateral cerebral ventricle and femoral artery and electrodes in AHA or PHA areas received intracerebral (ICV) administration of naloxone or clonidine prior to hypothalamic stimulation. AHA and PHA stimulation with current strength from 0.5 to 2.0 mA produced a significant (p < 0.05) and dose dependent increase in BP and heart rate. Naloxone reduced the increase in BP with AHA stimulation at all but the highest stimulation current intensity. Clonidine also blunted the BP increase to AHA stimulation but to a lesser degree than naloxone. The combination of both naloxone and clonidine completely prevented the increase in BP even at high current intensities. Both naloxone and clonidine prevented the increase in heart rate with AHA stimulation. In contrast to AHA stimulation, naloxone did not alter the BP increase produced by PHA stimulation while clonidine prevented the effects of PHA stimulation. Heart rate did not increase with PHA stimulation. These data suggest that (i) the mechanisms involved in the hypertensive response to AHA are different from that of PHA. (ii) the endogenous opioid system is more operative in mediating the BP elevation produced by AHA but not PHA stimulation (iii) activation of the central alpha adrenergic or imidazole receptors can suppress hypertensive response to both AHA and PHA but is more effective for PHA than AHA stimulation.
本研究的目的是，使用阿片受体拮抗剂纳洛酮来研究脑阿片受体的作用，以及使用激动剂可乐定来研究脑α2肾上腺素能受体和咪唑受体在电刺激前下丘脑前部（AHA）和下丘脑后部（PHA）区域所诱发的高血压和心动过速中的作用。体重300 - 400克、未麻醉且未束缚的Wistar大鼠，此前已将导管插入侧脑室和股动脉，并在AHA或PHA区域植入电极，在进行下丘脑刺激前接受脑室内（ICV）注射纳洛酮或可乐定。以0.5至2.0毫安的电流强度刺激AHA和PHA会导致血压和心率显著（p < 0.05）且呈剂量依赖性升高。除了最高刺激电流强度外，纳洛酮在所有刺激电流强度下均能减轻AHA刺激引起的血压升高。可乐定也能减弱AHA刺激引起的血压升高，但程度小于纳洛酮。即使在高电流强度下，纳洛酮和可乐定联合使用也能完全阻止血压升高。纳洛酮和可乐定均能阻止AHA刺激引起的心率升高。与AHA刺激不同，纳洛酮不会改变PHA刺激引起的血压升高，而可乐定可阻止PHA刺激的作用。PHA刺激不会引起心率升高。这些数据表明：（i）对AHA高血压反应的机制与PHA不同。（ii）内源性阿片系统在介导AHA而非PHA刺激产生的血压升高方面作用更大。（iii）中枢α肾上腺素能或咪唑受体的激活可抑制对AHA和PHA的高血压反应，但对PHA刺激比对AHA刺激更有效。
