激活脑内交感抑制系统防治高血压、心肌缺血的作用机制

The influence of activation of sympathetic inhibitory system in the brain on prevention and treatment of hypertension and cardiac ischemia was observed, and its mechanisms were anglicized by using techniques of physiological, pharmacological, morphological, molecular biological sciences, and etc. The results are as followings: (1) In stress-induced hypertensive and cardiac ischemia rats, electroacupuncture (EA) of Zusanli acupoint could reverse the increment of blood pressure (BP) and cardiac functions, and improve their condition of cardiac ischemia. Microinjection of nitric oxide (NO) synthase inhibitor into the ventral periaqueductal gray matter (vPAG) could attenuate the inhibition of EA. These results suggest that the effect of EA is mediated by the activation of sympathetic inhibitory system via NO in the vPAG. (2) Electric stimulation of the deep peroneal nerve (DPN) could reverse the increment of BP in stress-induced hypertensive rats. EA at Neiguan-Jianshi aucpoints could abolish the pressor response induced by inflation of the stomach, whereas microinjection of naloxone into the rostral ventrolateral medulla (rVLM) could attenuate the depressor effects induced by somatic nerve (e.g. DPN) inputs and EA. These results suggest that the depressor response is mediated by activation of endogenous opioid receptors. The further studies indicated that b-endorphin and enkephalin and their corresponding receptors (m and d opioid receptor, respectively) in the rVLM may play an important role in the modulation of cardiovascular reflex responses by EA, and dynorphin and its corresponding receptor (k receptor) may not involve these responses. (3) Immunofluorrescence double labeling combined with confocal microscopic observation demonstrated that the majority of the glutamatergic, g-aminobutyric acid (GABA) -ergic and tyrosine hydroxylase positive neurons in the rVLM coexist with angiotensin II (ANG II) type 1 receptor (AT1) in both Wistar rats and spontaneously hypertensive rats (SHR). Immunohistochemistry combined with image analytic observation demonstrated that the mean optical density of AT1 receptor on the neuron surface in the rVLM is higher in SHRs than that in Wistar rats. These results suggest that higher expression of AT1 receptor on the membrane in SHRs may be related to their increased sensitivity to the acute stimulation of ANG II. The further experiments indicated that ANG II induced glutamate release in the spinal cord might arise from the AT1 receptor-containing glutamatergic spinally projecting neurons in the rVLM. The excitatory effect of ANG II onto the neurons in the rVLM may be through stimulating the release of excitatory transmitters by presynaptic neurons and (or) enhancing the responsibility of excitatory postsynaptic receptor (AT1 receptor). (4) Microinjection of ANG- (1-7) into the rVLM could elevate arterial pressure accompanied by an increase in the release of excitatory amino acid glutamate in rat rVLM. EA at Zusanli acupoint could attenuate the above action of ANG- (1-7). Whereas, microinjection of a selective antagonist of ANG- (1-7) receptor ANG 779 into the rVLM caused an opposite effect, i.e. attenuated arterial pressure accompanied by a decrease in the release of excitatory amino acid glutamate and an increase in the release of inhibitory amino acid glycine and GABA. Bilateral application of EA at Zusanli acupoint could attenuate the inhibitory effect of ANG 779 also. (5) Microinjection of antagonists of glutamatergic receptors into the caudal ventrolateral medulla (cVLM) could significantly block the depressor response elicited by the greater splanchnic nerve (GSPL) afferent stimulation. Electrical stimulation of the GSPL inputs excited the majority of cardiovascular neurons in the cVLM, which suggests that the neurons and glutamatergic receptors in the cVLM are involved in the sympathetic inhibitory activities. (6) Microinjection of melatonin (MT) into the anterior hypothalamic area (AHA) could cause a decrease in arterial pressure, pretreated with MT1 receptor antagonist luzindole could com

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