猫头端延髓腹外侧区微量注射内皮素—1对其血压和心率的影响

为了探讨内皮素-1在头端延髓腹外侧区(the rostral ventrolateral medulla, rVLM)对心血管活动的影响。我们使用立体定位技术和微量注射的方法,用15只猫,观察了内皮素-1在该处对动脉血压(AP)、心率(HR)的影响。结果发现,随着内皮素-1剂量的增加,AP和HR也明显地升高和加快。     

Hypertensive response following stimulation of opiate receptors in the caudal ventrolateral medulla

In urethane-anesthetized rats, vasodepressor neuron pools were located bilaterally in and adjacent to the A1 area of the ventrolateral medulla by injecting the neuroexcitatory amino acid, L-glutamate. Ventrolateral vasodepressor areas included the caudalateral part of the nucleus reticularis gigantocellularis, the rostrolateral part of the nucleus reticularis ventralis, and the dorsal nucleus reticularis lateralis. In the ventrolateral vasodepressor areas L-glutamate elicited a transient fall in blood pressure (BP) and heart rate (HR). The opiate agonist (D-ala2-met5)-enkephalinamide (DAME) was used to stimulate opiate receptors in vasodepressor sites, identified with L-glutamate. In these sites, bilateral injections (0.1 microliter/site) of DAME caused a dose-related (2.5-500.0 ng) increase in blood pressure and heart rate, as well as exaggeration of the response to occlusion of the carotid. The effects of DAME on blood pressure were completely abolished by alpha-adrenergic blockade (phentolamine, 2 mg/kg, i.v.) and all effects of DAME were reversed by the administration of naloxone HCl (1 mg/kg, i.v.). Naloxone reversal was accompanied by an unexpected "rebound" hypertension. Saline had no significant effects when injected, or administered intravenously, in the absence or presence of DAME. It was concluded that stimulation of opiate receptors in the ventrolateral vasodepressor areas activated sympathetic outflow. An enkephalinergic system in this area of the brain stem may serve to modulate blood pressure, heart rate and cardiovascular reflexes.     

Role of nitric oxide on pressor mechanisms within the dorsomedial and rostral ventrolateral medulla in anaesthetized cats

1. The role of nitric oxide (NO) in central cardiovascular regulation and the correlation between NO and glutamate-induced mechanisms is not clear. Microinjection of glutamate (3 nmol/30 nL) into dorsomedial medulla (DM) and rostral ventrolateral medulla (RVLM) increased arterial blood pressure (BP) and sympathetic vertebral nerve activity (VNA). Thus, in the present study, we examined the modulation by NO of glutamate-induced pressor responses in the DM and RVLM of cats. 2. Histochemical methods using nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) as a marker to stain neurons containing NO synthase (NOS), showed positive findings of NOS in both the DM and RVLM. 3. Microinjection of N(G)-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, into the DM or RVLM did not alter resting BP and VNA, but it did cause a dose-dependent attenuation of glutamate-induced pressor responses. Interestingly, the increase in NO levels that resulted from pretreatment with L-arginine (L-Arg) or sodium nitroprusside (SNP) did not alter resting BP and VNA, but still inhibited glutamate-induced pressor responses in the DM and RVLM in a dose-dependent manner. 4. We also examined whether NO modulated the pressor responses induced by activation of different excitatory amino acid receptors. N-Methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA) were used. Consistent with the results from the initial glutamate studies, we observed that not only L-NAME, but also L-Arg and SNP attenuated pressor responses induced by NMDA and AMPA. No difference was found between the effects of NO on NMDA- and AMPA-induced pressor responses. 5. To investigate the possibility of a loss of agonist selectivity, the effects of D-2-amino-5-phosphonovalerate (D-AP5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) on AMPA and NMDA responses in the DM were examined. The results showed that CNQX did not alter NMDA-induced pressor responses, while D-AP5 failed to alter AMPA-induced responses. 6. Our results suggest that activation of the glutamate-induced pressor mechanism is regulated by changes in NO levels in the DM and RVLM. This implies that NO may play a permissive role to allow operation of the glutamate-activation mechanism.     

Blockade of excitatory amino acid receptors in the ventrolateral medulla does not abolish the cardiovascular actions of l-glutamate

Summary Injection of l-glutamate into the caudal ventrolateral medulla reduces arterial pressure while injection of l-glutamate into the rostral ventrolateral medulla increases arterial pressure. The present experiments were undertaken to determine whether blockade of excitatory amino acid receptor subtypes in the ventrolateral medulla affects the excitatory action of l-glutamate.In the rabbit and rat caudal ventrolateral medulla, injection of either dl-2-amino-5-phosphonovaleric acid (APV), an N-methyl-d-aspartic acid (NMDA) antagonist, or 6,7-dinitroquinoxaline-2,3-dione (DNQX), an -amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist, increased arterial pressure. Conversely, in the rostral ventrolateral medulla these agents decreased arterial pressure. In the rabbit caudal ventrolateral medulla, injection of APV totally blocked the depressor response to NMDA, and injection of DNQX totally blocked the depressor response to either kainic acid or AMPA. Injection of both APV and DNQX abolished the effects of NMDA, kainic acid and AMPA. However caudal ventrolateral medulla injection of either APV or DNQX, or combined injection of both antagonists, did not affect the relationship between the dose of l-glutamate and the fall in arterial pressure. Similarly, in the rat, combined excitatory amino acid receptor blockade failed to reduce the depressor effect of injected l-glutamate to the caudal ventrolateral medulla. The pressor effect of l-glutamate in the rabbit rostral ventrolateral medulla, when expressed as percentage of baseline level, was unchanged by combined excitatory amino acid receptor blockade.Our results provide evidence that both NMDA and non-NMDA receptors in the caudal ventrolateral medulla and the rostral ventrolateral medulla are tonically activated. If l-glutamate is the endogenous ligand in either the caudal ventrolateral medulla or the rostral ventrolateral medulla, its action must at least partially be via a non-NMDA, non-AMPA receptor.Correspondence to Z. J. Gieroba at the above address     

Cardiovascular response to injections of enkephalin in the pressor area of the ventrolateral medulla

The cardiovascular effects of the injection of an enkephalin analogue, [D-ala2-met5]enkephalinamide (DAME) into the pressor area of the rostral ventrolateral medulla were studied in urethane-anesthetized and decerebrate rats. The excitatory amino acid L-glutamate was used to identify the ventrolateral medulla. The pressor responses to L-glutamate were elicited from an area that included the nucleus reticularis gigantocellularis, the medial aspect of the nucleus reticularis parvocellularis and the dorsal portion of the nucleus reticularis lateralis. Injection (0.1 microliter volume) of DAME (2.5-500.0 ng/site) into the ventrolateral medulla elicited a dose-related decrease in arterial blood pressure and heart rate and attenuated the carotid occlusion response (COR). Control injections (0.1-0.2 microliter vol) of saline into the same area failed to produce any response. The specificity of this opiate response was tested with naloxone HCl, an opiate antagonist, which prevented, as well as reversed, the action of DAME both by intravenous (i.v.) administration and by injection into the ventrolateral medulla. It was concluded that the ventrolateral medulla plays a role in the generation of vasomotor tone and that stimulation of opiate receptors in this area by an enkephalin analogue produced hypotension, bradycardia and modification of cardiovascular reflexes.     

N-METHYL-d-ASPARTATE RECEPTORS IN THE SPINAL CORD MEDIATE PRESSOR RESPONSES TO STIMULATION OF THE ROSTRAL VENTROLATERAL MEDULLA IN THE RAT

1. Activation of bulbospinal neurons projecting from the C1 area of the rostral ventrolateral medulla evokes a pressor response. The nature of the neurotransmitters involved in mediating this response at spinal cord level has not been established. 2. Amino acid antagonists were introduced into the spinal subarachnoid space to investigate the role of spinal amino acid receptors in mediating this pressor response in the anaesthetized rat. 3. Intrathecal administration of the amino acid receptor antagonists 2-amino-phosphono valeric acid (2APV), gamma-glutamyl glycine, kynurenate or glutamic acid diethylester (GDEE) attenuated the pressor responses to stimulation of the C1 area. These compounds have been shown to antagonize N-methyl-D-aspartate (NMDA) sensitive receptors. 4. Intrathecal administration of 2APV significantly attenuated the increase in blood pressure produced by injection of NMDA into the spinal subarachnoid space. 5. These results suggest that the pressor response produced by stimulation in the area of the C1 neurons in the rostral ventrolateral medulla of the rat is mediated at least in part by NMDA receptors in the spinal cord.     

Ipsilateral but not contralateral blockade of excitatory amino acid receptors in the caudal ventrolateral medulla inhibits aortic baroreceptor reflex in rats

Summary The caudal ventrolateral medulla (CVLM) contains vasodepressor neurons which, when activated, decrease vasomotor tone. To investigate whether excitatory amino acid receptors in the CVLM of the rat are involved in mediation of the aortic baroreceptor reflex, we microinjected amino acid antagonists unilaterally into the CVLM and examined their effects on the depressor response to electrical stimulation of the aortic nerve which contains mainly baroreceptor afferent fibers in rats. Male Wistar rats were anaesthetized with urethane, paralyzed and artificially ventilated. To block reflex vagal effects, methylatropine (1 mg/kg) was given intravenously. Kynurenate (227 ng), an excitatory amino acid antagonist, injected ipsilaterally but not contralaterally into the CVLM markedly inhibited the depressor response to aortic nerve stimulation, while both injections produced a similar small increase in basal blood pressure. Muscimol (1 ng), a GABA receptor agonist, injected ipsilaterally into the CVLM partly inhibited the baroreflex response, while it produced a moderate increase in basal blood pressure. 2-Amino-5-phosphonovalerate (APV) (10 ng), a N-methyl-d-aspartate (NMDA) receptor antagonist, and MK-801 (30 ng), a NMDA receptor channel blocker, partly inhibited the baroreflex response. MK-801 (30 ng) injected into the CVLM reduced the depressor response to the NMDA receptor agonist NMDA (0.3 ng) but not to the quisqualate receptor agonist quisqualate (0.1 ng) and the kainate receptor agonist kainate (0.1 ng), while kynurenate (227 ng) inhibited the depressor response to all three excitatory amino acid receptor agonists. These findings provide further evidence for the presence of excitatory amino acid receptors involved in mediating the aortic baroreceptor reflex in the rat CVLM. It appears that neurons other than the vasodepressor neurons in the CVLM, at least in part, play a role in transmitting the aortic baroreceptor reflex. In addition, both NMDA and non-NMDA receptors may be responsible for the mediation of the reflex. Send offprint requests to T. Kubo at the above address     

Inhibitory effects of angiotensin II on barosensitive rostral ventrolateral medulla neurons of the rat

1. The brain renin-angiotensin system can influence arterial baroreceptor reflex control of blood pressure (BP) through both direct and indirect effects on sympathetic premotor neurons of the rostral ventrolateral medulla (RVLM). The present study examined the direct effect of angiotensin (Ang) II applied by microiontophoresis on the ongoing activity of single RVLM neurons. 2. In 26 urethane-anaesthetized Wistar rats, recordings of single unit activities of barosensitive RVLM neurons were made from one barrel of a six-barrel micropipette assembly. The other five barrels were filled with either L-glutamate, AngII, valsartan (an AT1 receptor antagonist), PD 123177 (an AT2 receptor antagonist) and saline. All drugs were applied by microiontophoresis. 3. Mean BP was 83 +/- 3 mmHg. Application of AngII inhibited the ongoing activity of RVLM neurons, identified as barosensitive because their activity was inhibited by a phenylephrine- induced increase in BP, from 12.6 +/- 1.5 to 5.4 +/- 1.1 Hz (n=24; P < 0.001). Angiotensin II also inhibited the glutamate-evoked excitation of barosensitive RVLM neurons from 15 +/- 3 to 5.8 +/- 2.0 Hz (n=6; P < 0.001). Valsartan significantly increased neuronal activity from 9.5 +/- 2.3 to 13.5 +/- 3.2 Hz (n=7, P < 0.01), whereas PD 123177 significantly decreased neuronal activity from 13.5 +/- 3.5 to 9.9 +/- 2.8 Hz (n=13; P < 0.01). 4. The results suggest that AngII exerts a tonic inhibitory effect on barosensitive RVLM neurons, which is presumably mediated through AT1 receptor stimulation.     

Responses to microinjections of endomorphin and nociceptin into the medullary cardiovascular areas

1. Cardiovascular effects of microinjections of nociceptin and endomorphin-2 into the following medullary areas were studied in urethane-anaesthetized rats: chemoreceptor projection site (CPS), intermediate portion of the nucleus tractus solitarius (I-NTS), caudal ventrolateral medullary depressor area (CVLM) and rostral ventrolateral medullary pressor area (RVLM). 2. Microinjections of nociceptin or endomorphin-2 (0.6 mmol/L each) into the CPS and RVLM elicited depressor and bradycardic responses, whereas similar injections into the I-NTS and CVLM elicited pressor and tachycardic responses. 3. The mechanism of cardiovascular responses to microinjections of these opioid peptides into different medullary areas involved in cardiovascular function can be postulated as follows: the direct effect of nociceptin and endomorphin-2 on neurons is usually inhibitory. Because the activation of CPS and RVLM by microinjections of L-glutamate results in pressor and tachycardic responses, inhibition of these areas by nociceptin and endomorphin-2 elicits depressor and bradycardic responses. Similarly, activation of neurons in the I-NTS and CVLM by microinjections of L-glutamate elicits depressor and bradycardic responses. Therefore, inhibition of these areas by microinjections of these opioid peptides elicits an increase in blood pressure and heart rate.     

Excitatory amino acid receptors in the rostral ventrolateral medulla mediate hypertension induced by carotid body chemoreceptor stimulation

The rostral ventrolateral medulla (RVLM) is involved in the mediation of cardiovascular responses to peripheral chemoreceptor stimulation. To investigate whether excitatory amino acid inputs in the RVLM are related to the responses to chemoreceptor stimulation, we microinjected kynurenate, an amino acid antagonist, unilaterally into the RVLM and examined its effects on the pressor response to stimulation of carotid body chemoreceptors. Male Wistar rats were anesthetized with urethane, paralyzed and artificially ventilated. The carotid chemoreceptors were stimulated with isotonic solutions of inorganic phosphate solution.Stimulation of carotid body chemoreceptors produced increases in blood pressure. Kynurenate injected ipsilaterally but not contralaterally into the RVLM markedly inhibited the pressor response to chemoreceptor stimulation. In rats with spinal transection, stimulation of carotid body chemoreceptors also produced increases in blood pressure. The pressor response in rats with spinal transection was inhibited by intravenous injection of a vasopressin antagonist or by kynurenate injected ipsilaterally into the RVLM. Kynurenate injected into the RVLM inhibited the pressor response to NMDA, AMPA and kainate but not to acetylcholine in intact rats. These findings indicate that excitatory amino acid receptors are involved in mediating the pressor response to carotid body chemoreceptor stimulation in the rat RVLM. It appears that the chemoreceptor stimulation produces an increase in vasopressin release and the enhancement of vasopressin release is also mediated by an increase in excitatory amino acid inputs in the RVLM. Correspondence to: T. Kubo at the above address     

Glutamate circuits in selected medullo-spinal areas regulating cardiovascular function

1. The importance of the medullo-spinal neuronal pools in the regulation of cardiovascular function has been known for a long time. However, important groups of these neurons, interconnections between them and the neurotransmitters released at their projections have been identified with certainty only during the past two decades. 2. Some of the medullo-spinal neuronal pools mediating cardiovascular function include the nucleus tractus solitarius, caudal ventrolateral medullary depressor area, rostral ventrolateral medullary pressor area, nucleus ambiguus and intermediolateral cell column of the thoracolumbar spinal cord. Interactions between these selected neuronal groups and neurotransmitters in the pathways connecting them are discussed in the present short review.     

大鼠尾端延髓腹外侧区非NMDA受体参与压力反射传导

目的:探讨大鼠尾端延髓腹外侧区(CVLM)非N-甲基-D-天门冬氨酸(non-NMDA)受体在介导压力反射中的作用。方法:在戊巴比妥钠和氨基甲酸乙酯麻醉、制动和人工呼吸的SD大鼠,观察CVLM内局部给予non-NMDA受体选择性阻断剂CNQX对刺激主动脉神经导致的减压反应和头端延髓腹外侧区(RVLM)神经元的压力敏感性的作用。结果:双侧CVLM微量注射CNQX(每侧200 pmol/100 nL)后明显(P<0.01)地增高基础血压(BP)和心率,而且显著(P<0.01)地减弱刺激主动脉神经导致的降压反应。单侧CVLM内给予CNQX(200 pmol/100 nL)明显(P<0.01)增高同侧RVLM压力敏感性神经元的基础放电频率,但显著(P<0.01)减弱刺激主动脉神经和升高血压导致的神经元活动的抑制效应和部分抑制神经元的心性节律。结论:大鼠尾端延髓腹外侧区non-NMDA受体在维持紧张性兴奋的心血管活动和传递压力感受器信息中具有重要的意义。     

Nitric oxide modulates cardiovascular function in the rat by activating adenosine A2A receptors and inhibiting acetylcholine release in the rostral ventrolateral medulla

1. Nitric oxide (NO), a gas transmitter, modulates many physiological processes, including the central regulation of cardiovascular activity. However, the mechanisms underlying the regulation of cardiovascular activity remain relatively unexplored. In the present study, we hypothesized that central NO-dependent sympathetic inhibition is mediated by activation of adenosine A(2A) receptors (A(2A)R) and inhibition of acetylcholine (ACh) release in the rostral ventrolateral medulla (RVLM). 2. L-Arginine (L-Arg; an NO donor; 100 nmol/100 nL) was microinjected into the RVLM of male Sprague-Dawley rats and heart rate variability (HRV) was assessed as an index of cardiac sympathovagal balance. Following microinjection of L-Arg, decreases were seen in mean arterial pressure (MAP), heart rate (HR) and the ratio of the low- to high-frequency components (LF/HF) of HRV. Pretreatment of rats with SCH58261 (40 pmol/60 nL into the RVLM), a competitive antagonist of the A(2A) R, attenuated these effects. 3. Western blot analysis and ELISA revealed that adenosine and A(2A)R levels increased in the RVLM following L-Arg microinjection, whereas ACh and muscarinic M(1) receptor levels decreased significantly, in parallel with the cardiovascular responses to L-Arg microinjection. The decrease in ACh levels was abolished by SCH58261 pretreatment. 4. Microinjection of N(G)-nitro-L-arginine methyl ester (a non-selective inhibitor of NO synthase; 15 nmol/100 nL) into the RVLM significantly increased MAP, HR and sympathetic activity, as evidenced by HRV (LF, HF and the LF/HF ratio were all increased). 5. The results indicate that the central NO/NO synthase system in the RVLM may modulate cardiovascular activity by activating the A(2A)R, which subsequently inhibits activation of the muscarinic M(1) receptor.     

Differential contributions of NOS isoforms in the rostral ventrolateral medulla to cardiovascular responses associated with mevinphos intoxication in the rat

The organophosphate poison mevinphos (Mev) elicits cardiovascular responses via nitric oxide (NO) produced on activation of M2 muscarinic receptors (M2R) in the rostral ventrolateral medulla (RVLM), where sympathetic vasomotor tone originates. This study further evaluated the contribution of nitric oxide synthase (NOS) isoforms at the RVLM to this process, using adult Sprague-Dawley rats. Bilateral co-microinjection into the RVLM of the selective NOS I inhibitor (250 pmol), 7-nitroindazole or N(omega)-propyl-L-arginine antagonized the initial sympathoexcitatory cardiovascular responses to Mev (10 nmol). Co-administration of a selective NOS II inhibitor, N6-(1-iminoethyl)-L-lysine (250 or 500 pmol) further enhanced these cardiovascular responses and reversed the secondary sympathoinhibitory actions of Mev. A potent NOS III inhibitor, N5-(1-iminoethyl)-L-ornithine (46 or 92 nmol) was ineffective. We also found that M2R co-localized only with NOS I- or NOS II-immunoreactive RVLM neurons. Furthermore, only NOS I or II in the ventrolateral medulla exhibited an elevation in mRNA or protein levels during the sympathoexcitatory phase, with further up-regulated synthesis of NOS II during the sympathoinhibitory phase of Mev intoxication. We conclude that whereas NOS III is not engaged, NO produced by NOS I and II in the RVLM plays, respectively, a sympathoexcitatory and sympathoinhibitory role in the cardiovascular responses during Mev intoxication.     

CVLM咪唑啉-I和α_2-肾上腺素受体共同参与可乐定的降压效应

目的　探讨大鼠尾端延髓腹外侧区 (CVLM)咪唑啉 I受体 (I1R)和α2 肾上腺素受体 (α2 AR)在介导可乐定中枢降压机制中的作用。方法　在氨基甲酸乙酯麻醉SD大鼠中 ,观察CVLM内局部给予I1R和α2 AR阻断剂后对基础血压(BP)、心率 (HR)以及外周给予可乐定导致降压效应的变化。结果　双侧CVLM分别微量注射选择性α2 AR阻断剂育亨宾 (单侧剂量 5 0 0 pmol·L-1,10 0nl,n =8)或I1R和α2 AR混合性阻断剂idazoxan(单侧剂量 2nmol·L-1,10 0nl,n =10 )后不仅明显降低BP和HR(P <0 0 1) ,而且能明显减弱静脉给予可乐定 (5 μg·kg-1)导致的降压效应 (P <0 0 1) ,此外 ,idazoxan对可乐定降压效应的减弱作用高于育亨宾 (P <0 0 1)。结论　CVLM内I1R和α2 AR共同参与维持紧张性心血管活动和介导可乐定的降压效应     

Differential regulation of brown adipose and splanchnic sympathetic outflows in rat: roles of raphe and rostral ventrolateral medulla neurons

1. The medullary premotor neurons determining the sympathetic outflow regulating cardiac function and vasoconstriction are located in the rostral ventrolateral medulla (RVLM). The present study sought evidence for an alternative location for the sympathetic premotor neurons determining the sympathetic nerve activity (SNA) controlling brown adipose tissue (BAT) metabolism and thermogenesis. 2. The tonic discharge on sympathetic nerves is determined by the inputs to functionally specific sympathetic preganglionic neurons from supraspinal populations of premotor neurons. Under normothermic conditions, BAT SNA was nearly silent, while splanchnic (SPL) SNA, controlling mesenteric vasoconstriction, exhibited sustained large-amplitude bursts. 3. The rostral raphe pallidus (RPa) contains potential sympathetic premotor neurons that project to the region of sympathetic preganglionic neurons in the thoracic spinal cord. Disinhibition of neurons in RPa elicited a dramatic increase in BAT SNA, with only a small rise in SPL SNA. 4. Splanchnic SNA was strongly influenced by the baroreceptor reflex, as indicated by a high coherence with the arterial pressure wave, a significant amplitude modulation over the time-course of the cardiac cycle and a marked inhibition of SPL SNA during a sustained increase in arterial pressure. When activated, the bursts in BAT SNA exhibited no correlation with arterial pressure and were not affected by increases in arterial pressure. 5. Because these characteristics and reflex responses in sympathetic outflow have been shown to arise from the on-going or altered discharge of sympathetic premotor neurons, the marked differences between SPL and BAT SNA provide strong evidence supporting the hypothesis that vasoconstriction and thermogenesis (metabolism) are controlled by distinct populations of sympathetic premotor neurons, the former in the RVLM and the latter, potentially, in the RPa.     

Effects of melatonin on blood pressure in stress-induced hypertension in rats

Melatonin, acting through its receptors, is involved in numerous physiological processes, including blood pressure (BP) regulation. In present study, the effect of melatonin inhibition on stress-induced hypertension was investigated. The hypertensive model consisted of male Sprague-Dawley rats subjected to electrical foot-shock combined with noise. Microinjection of melatonin (0.1 and 1.0 mmol/L) into the anterior hypothalamic area (AHA) produced a fall in BP in nomortensive rats and stress-induced hypertensive rats (SIHR). Luzindole (10 mmol/L), a competitive antagonist of melatonin MT1 and MT2 receptors, almost completely abolished the depressor effect of melatonin, the MT2 receptor-specific antagonist 4-phenyl-2-propionamidotetralin (10 mmol/L) partially blocked (by approximately 60%) the depressor effect of melatonin, whereas the MT3 receptor-selective antagonist prazosin (10 mmol/L) failed to antagonize the effects of melatonin. Brain microdialysis was performed in the AHA and the rostral ventrolateral medulla (RVLM). Melatonin and amino acids in the dialysate samples collected were detected by high-performance liquid chromatography combined with fluorescence detection. The results indicated that melatonin concentrations in the AHA were reduced in SIHR. Microinjection of melatonin into the AHA decreased glutamate release and increased GABA and taurine release in the RVLM, which were paralleled by a decrease in arterial pressure. The mRNA expression of MT2 in the AHA of SIHR was higher than that in normotensive control rats, whereas there was no significant difference in MT1 mRNA expressin between the two groups. The results of the present study suggest that both a decrease of melatonin and an increase in the MT2 receptor in the AHA are involved in the manifestation of stress-induced hypertension. Both MT1 and MT2 receptors participated in the antihypertensive effect of melatonin in the AHA. The antihypertensive effect of melatonin was related to the decreases in the excitatory amino acid glutamate and increases in the inhibitory amino acids taurine and GABA in the RVLM.     

Contribution of peroxynitrite to fatal cardiovascular depression induced by overproduction of nitric oxide in rostral ventrolateral medulla of the rat

We evaluated the contribution of peroxynitrite to the fatal cardiovascular depression induced by overproduction of nitric oxide (NO) after activation of inducible NO synthase (iNOS) in the rostral ventrolateral medulla (RVLM), the origin of sympathetic vasomotor tone. In Sprague-Dawley rats maintained under propofol anesthesia, microinjection of E. coli lipopolysaccharide (LPS) bilaterally into the RVLM elicited significant hypotension, bradycardia, reduction in sympathetic vasomotor tone and mortality. There was also a discernible elevation of iNOS expression in the ventrolateral medulla, followed by a massive production of nitrotyrosine, an experimental index for peroxynitrite. Co-administration bilaterally into the RVLM of the selective iNOS inhibitor, S-methylisothiourea (50, 100 or 250 pmol), an active peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis- (N-methyl-4'-pyridyl)-porphyrinato iron (III) (10 or 50 pmol), a peroxynitrite scavenger, L-cysteine (5, 50 or 100 pmol), or a superoxide dismutase mimetic, Mn(III)-tetrakis-(4-benzoic acid) porphyrin (1 or 10 pmol), significantly prevented mortality, reduced nitrotyrosine production and reversed the NO-induced cardiovascular suppression after application of LPS into the RVLM. We conclude that the formation of peroxynitrite by a reaction between superoxide anion and NO is primarily responsible for the fatal cardiovascular depression induced by overproduction of NO after activation of iNOS at the RVLM.     

猫延髓头侧腹外侧区注射内皮素-1对猫心血管活动的影响

研究内皮素－１（ＥＴ－１）在猫延髓头侧腹外侧区（ｒＶＬＭ）对心血管活动的影响．方法：采用脑立体定向和脑内微量注射技术．结果：ｒＶＬＭ内微量注射 ＥＴ－１（４μｍｏｌ·Ｌ－１, ０．５μＬ）后,平均动脉压（ＭＡＰ）升高（３．７±１．３）ｋＰａ,心率增加（２９±７）ｂｅａｔｓ·ｍｉｎ－１,肾神经活动增加 ４５％±１０％,量－效呈正相关．双颈部迷走神经切断后不影响上述结果．静脉预先给予酚妥拉明 ５ ｍｇ·ｋｇ－１能显著抑制ＥＴ－１的升压作用．血浆精氨酸升压素（Ａｒｇ）含量由（１２．４± ６． ５） ｎｇ· Ｌ－１增加到（７０．３± ２４． ２）ｎｇ·Ｌ－１,并与ＭＡＰ变化显著相关,使缺血心脏心律紊乱（ＨＲｈＤ）,ＨＲｈＤ出现在结扎后（４．８±２．９）ｍｉｎ,评分为 ４．４±１．６,与对照组差异显著．结论：ｒＶＬＭ内注射ＥＴ－１影响了心血管和交感神经活动的中枢调节。