下丘脑减压区神经降压素对压力感受性反射的影响

于大鼠双侧下丘脑前部减压区注射微量神经降素（ｎｅｕｒｏｔｅｎｓｉｎ，ＮＴ）及其抗血清（ａｎｔｉｎｅｕｒｏｔｅｎｓｉｎｓｅｒｕｍ，ＡＮＴＳ）．观察对压力感受性反射的影响。结果表明，大鼠双侧下丘脑前部减压区注入ＮＴ后，可明显抑制静脉注射新福林所致的升压反应（Ｐ＜０．０１），从而加强压力感受性反射的活动；而注射ＡＮＴＳ则产生相反结果（Ｐ＜０．０１）。揭示下丘脑前部减压区ＮＴ参与压力感受性反射的调节过程。     

高血压病左心室肥厚与血管活性物质的关系及依那普利干预

目的：探讨体循环血液中多种血管活性物质在高血压病左心室肥厚（ＬＶＨ）发生和依那普利（ｅｎａｌａｐｒｉｌ）逆转治疗中的作用。方法：测定高血压病患者４５例合并ＬＶＨ、４５例不合并ＬＶＨ及３０例正常人血流动力学和血浆５种血管活性物质，观察２７例高血压病患者合并ＬＶＨ依那普利治疗２４周后各项参数变化。结果：合并ＬＶＨ组收缩压、血浆内皮素、去甲肾上腺素、内源性洋地黄物质（ＥＤＬＳ）和心钠素高于不合并ＬＶＨ组（Ｐ＜０．０５～０．０１），血管紧张素Ⅱ高于正常人（Ｐ＜０．０１）；对１３个相关因素进行逐步回归分析表明，内皮素、血管紧张素Ⅱ和去甲肾上腺素对ＬＶＨ作用显著（复相关系数０．７６９，Ｐ＜０．００１）；内皮素、血管紧张素Ⅱ、去甲肾上腺素、ＥＤＬＳ之间呈正相关（Ｐ＜０．０５～０．０１）；依那普利干预后，ＬＶＨ消退，血压和血管活性物质同步下降（Ｐ＜０．０５～０．０１）。结论：体循环血液中多种血管活性物质含量改变及其相互作用可能共同参与高血压病ＬＶＨ的形成，依那普利消退ＬＶＨ的机制可能与降低这些物质有关。     

依那普利对充血性心力衰竭患者肾上腺素能通路作用的探讨

３０例充血性心力衰竭患者，应用依那普利口服治疗。３～４周后血淋巴细胞β受体密度上调（Ｐ＜０．０１）；血浆去甲肾上腺素、肾上腺素均下降（Ｐ＜０．０１和Ｐ＜０．０５）；血淋巴细胞内环磷酸腺苷含量下降（Ｐ＜０．０１）。表明依那普利对肾上腺素能通路起良好的调控作用。     

牛磺酸对糖尿病大鼠心肌组织肾素—血管紧张素系统的抑制作用

为探讨牛磺酸对糖尿病的治疗作用，在链脲佐菌素所致糖尿病大鼠模型中观察了大鼠心肌组织肾素血管紧张素系统（ＲＡＳ）的变化以及牛磺酸的治疗作用。结果表明，糖尿病大鼠较正常大鼠心肌组织ＲＡ，ＡＣＥ活性显著升高（Ｐ＜０．０１），ＡＴＩ和ＡＴＩＩ含量均明显增加（Ｐ＜０．０１）。牛磺酸治疗组大鼠较未治疗组大鼠上述各项指标均有不同程度的降低，其中ＡＣＥ活性和ＡＴＩ，ＡＴＩＩ含量的改变差异有显著性（Ｐ＜０．０５，Ｐ＜０．０１），ＲＡ改变差异无显著性。提示：心肌组织ＲＡＳ功能亢进参与糖尿病性心肌病发病过程。牛磺酸抑制心肌组织ＲＡＳ功能对减轻糖尿病心肌损害具有一定的临床治疗意义。     

慢性充血性心力衰竭患者心率变异性与病情的相关性分析

目的：为探讨心力衰竭（心衰）患者心率变异性与病情的关系。方法：本文采用时域及频域２种分析方法，对９２例心衰患者和５１例对照组健康人进行了心率变异性对比分析，并对部分患者（ｎ＝１０）及对照组健康人（ｎ＝２０）进行血浆儿茶酚胺（去甲肾上腺素、肾上腺素）浓度测定及心率变异性随访。结果：心衰患者的心率变异性显著低于对照组健康人；并且与病情及心功能明显相关（Ｐ＜０．０５～０．００１）；心衰患者中近期死亡者心率变异性进一步降低（Ｐ＜０．０５～０．００１）；心衰患者血浆去甲肾上腺素及肾上腺素浓度明显高于健康组（Ｐ＜０．０２～０．０１）。结论：心衰患者心率变异性降低提示，心衰患者心率变异性的数量变化，反应患者病情变化。高的血浆儿茶酚胺浓度间接说明了心衰患者心脏自主神经功能受损是神经激素系统持续激活的结果     

β内啡肽对慢性缺氧大鼠呼吸的影响

目的　探讨β内啡肽（βＥＰ） 在慢性缺氧大鼠呼吸调控中的作用。方法　采用放射免疫法测定慢性缺氧大鼠模型血浆及延髓、桥脑、下丘脑、中央灰质等神经核团中βＥＰ的含量变化，以及不同给药途径给予外源性βＥＰ对慢性缺氧大鼠呼吸功能的影响。正常大鼠侧脑室注射βＥＰ后，观察记录呼吸频率（ＲＲ） ；１０２ 只慢性缺氧大鼠随机分为：（１） 静脉组３６ 只，分别给予阿片受体拮抗剂纳洛酮（ＮＬＸ） 和不同剂量βＥＰ，记录ＲＲ 和潮气量（ＶＴ）；（２） 侧脑室组４８ 只，微量注射ＮＬＸ、βＥＰ，测定ＲＲ、ＶＴ及血气指标；（３） 孤束核组１８ 只，分别注射βＥＰ和人工脑脊液（ＡＣＳＦ） ，测定ＲＲ和ＶＴ。结果慢性缺氧模型延髓、桥脑、下丘脑、中央灰质和血浆βＥＰ的含量较对照组均显著升高（Ｐ＜０－０１）。给正常大鼠侧脑室注射βＥＰ后，ＲＲ 显著下降（ Ｐ＜ ０－０５） 。慢性缺氧大鼠静脉给予不同剂量βＥＰ和ＮＬＸ后，ＲＲ和ＶＴ 变化差异无显著性（Ｐ＞０－０５）。侧脑室注射ＮＬＸ后，ＲＲ显著增高（ Ｐ＜０－０５）。侧脑室及孤束核注射βＥＰ后显著降低ＲＲ、ＶＴ。侧脑室注射ＮＬＸ３０ 分钟时ＭＶ／ＰａＣＯ２ 较对照组显著升高（ｔ＝２－７６ ，     

益心Ⅰ和益心Ⅱ治疗慢性肺心病心衰的临床及实验研究

本文以口服益心Ⅰ、益心Ⅱ治疗２５例慢性肺心病心衰患者，总有效率为９２％。实验表明：两药能明显抑制去甲肾上腺素引起兔肺动脉环收缩（Ｐ＜０．０１）；明显增加兔肾血流量及尿量（Ｐ＜０．０５，＜０．０１）；提高肺心病心衰患者的６－ｋｅｔｏ－ＰＧＦ１α（Ｐ＜０．０５），使血浆ＴＸＢ２／６－ｋｅｔｏ－ＰＧＦ１α降低并接近正常。提示两药治疗肺心病心衰可能通过扩张肺动脉，改善肾血流量及增加尿量，增加血浆ＰＧＩ２含量、恢复ＴＸＡ２／ＰＧＩ２的平衡。     

抑制NO合酶上调大鼠血管α1—肾上腺素受体和三磷酸肌醇受体

探讨ＮＯ系统和血管α１－肾上腺素受体α１－ＡＲ）及三磷酸肌醇受体（ＩＰ３Ｒ）系统在高血压发病中的相互作用。方法在常规饲食中加入Ｌ－ＮＡＭＥ喂饲大鼠１或４周制备大鼠高血压模型；应用放射性配基结合实验观察α１－ＡＲ及ＩＰ３Ｒ的变化。结果应用Ｌ－ＮＡＭＥ处理一周，大鼠动脉血压升高３０（２ｍｍＨｇ（Ｐ＜０．０５），血浆ＮＯｘ含量则下降２５％（Ｐ＜０．０５）。主动脉肌膜α１－ＡＲ及肌浆网ＩＰ３Ｒ密度分别增加１２％和４０％。Ｌ－ＮＡＭＥ处理４周，大鼠血压升高７５±８ｍｍＨｇ（Ｐ＜０．０１），血浆ＮＯｘ含量下降５０％（Ｐ＜０．０１），主动脉肌膜α１－ＡＲ及肌浆网ＩＰ３Ｒ密度分别较对照组高７３％和１３７％（Ｐ＜０．０１），此时尾动脉肌膜ＡＲ及肌浆网ＩＰ３Ｒ密度亦较对照组增加５５％和５６％（Ｐ＜０．０１）。结论提示长期抑制ＮＯＳ引起大鼠持续性高血压的同时，可致大鼠血管α１－ＡＲ及ＩＰ３Ｒ明显上调。     

碘对大鼠大脑去甲肾上腺素和多巴胺影响的实验研究

Ｗｉｓｔａｒ大鼠２个年龄组，每个年龄段随机分为３组。实验１组给碘１．６７μｇ／ｋｇ体重，实验共进行３０天。实验结果：大鼠补碘后，体重为１２０～１５０ｇ的大鼠经３０天喂养后，脑内去甲肾上腺素含量高、低剂量组均与对照组有显著性差异（Ｐ＜０．００１，Ｐ＜０．００２）；体重为５０～７０ｇ的大鼠经３０天喂养后，高剂量组与对照组有显著性差异（Ｐ＜０．０５）。多巴胺含量，２个年龄段大鼠经３０天喂养后，均为高剂量组与对照组有显著性差异（Ｐ＜０．０５）。结论：健康发育的大鼠补碘一段时间后，可提高其大脑神经递质去甲肾上腺素和多巴胺的释放     

经血管转染iNOS基因对大鼠的降血压作用

目的研究经大鼠尾静脉转染ｉＮＯＳ基因对大鼠血压的影响。方法从尾静脉注射经磷酸钙包裹的载有人类全长ｉＮＯＳｃＤＮＡ的表达质粒进入大鼠体内后，检测大鼠血压的改变及培养大鼠腹腔巨噬细胞上清液中ＮＯ的含量。结果（１）大鼠的血压从转染前的１８４．４７±７．８５ｍｍＨｇ，１６２．２３±１４．１３ｍｍＨｇ，于转染后第２天分别下降为１４５．２４±１３．４３ｍｍＨｇ（Ｐ＜０．０５，ｎ＝５）及１２８．９０±１５．０６ｍｍＨｇ（Ｐ＜０．０５，ｎ＝５），血压降低能维持６天以上；（２）转染ｉＮＯＳ基因使培养大鼠腹腔巨噬细胞上清液中ＮＯ水平由０．１２２±０．０１４ＯＤ值上升为０．２５４±０．０３１ＯＤ值３３（Ｐ＜０．０１，ｎ＝５，转染后第３天）及由０．１２５±０．０２１ＯＤ值上升为０．２０９±０．０１９ＯＤ值（Ｐ＜０．０１，ｎ＝５，转染后第６天）。结论静脉注射经磷酸钙包裹的ｉＮＯＳ基因进入大鼠体内，能成功地转染巨噬细胞，也可能转染其他具有吞噬功能的细胞，并表达其产物，使ＮＯ生成持续增加，导致血管舒张，血压降低，并在一段时间内维持较低水平。本实验为整体动物心血管系统的基因转染研究展示一种较为简便的方法     

Job strain, ethnicity, and sympathetic nervous system activity

Several studies have demonstrated that blacks have heightened pressor sensitivity in response to the alpha-agonist, phenylephrine. However, studies examining whether psychosocial factors contribute to this difference are scarce. We examined the effects of job strain on pressor sensitivity in 76 whites and 46 blacks who were enrolled in a study of stress, sleep, and blood pressure. Responses to phenylephrine were examined at an inpatient clinical research center. After a 3-minute baseline period, a 100-microgram phenylephrine bolus was administered to participants intravenously. To measure catecholamines, 24-hour urine samples were also collected from participants. There was a significant relationship between job strain and pressor sensitivity, such that individuals with low decisional control and high job demands experienced a greater increase in diastolic pressure after receiving phenylephrine. Low decisional control was also associated with decreased baroreflex sensitivity. There was an interaction between ethnicity and job control on blood pressure responses to phenylephrine and on 24-hour urinary norepinephrine levels. Blacks who perceived less control experienced a greater increase in diastolic pressure after receiving phenylephrine and had elevated norepinephrine levels. These findings suggest possible mechanisms by which job strain may be associated with cardiovascular disease.     

Brainstem norepinephrine neurons mediate ethanol-evoked pressor response but not baroreflex dysfunction

BACKGROUND: Ethanol elicits strain-dependent blood pressure and baroreflex sensitivity responses in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats; the mechanisms underlying these divergent effects are not clear. The authors tested the hypothesis that differential neuronal actions of ethanol may account for these strain-dependent responses. To this end, the authors investigated the direct effects of ethanol on norepinephrine (NE)-containing neurons in the rostral ventrolateral medulla (RVLM), which modulate sympathetic neuronal activity, and on c-Jun-expressing neurons in the nucleus tractus solitarius (NTS), whose activity is inversely correlated with baroreflex sensitivity. METHODS: In a newly developed model system in conscious, freely moving rats, the effect of intra-RVLM or intra-NTS ethanol was investigated on neuronal NE at the microinjection site (in vivo electrochemistry), blood pressure, heart rate, spontaneous baroreflex sensitivity, and c-Jun expression in the NTS. RESULTS: Ethanol (1, 5, or 10 microg) microinjection into the RVLM elicited dose-dependent increases in RVLM NE and blood pressure in SHRs but not in WKY rats. Ethanol had no effect on the activity of the NE-containing neurons in the NTS of either strain. However, baroreflex dysfunction elicited by intra-NTS ethanol in conscious WKY rats was associated with enhanced expression of c-Jun in the NTS. CONCLUSIONS: (1) Ethanol activation of the NE-containing neurons in the RVLM of SHRs contributes to the centrally mediated pressor response, (2) the NE-containing neurons in the NTS are not involved in ethanol-induced baroreflex dysfunction, and (3) direct activation of the c-Jun-containing neurons in the NTS is implicated in baroreflex dysfunction elicited by ethanol in normotensive rats.     

Arterial baroreflex sensitivity, plasma catecholamines, and pressor responsiveness in essential hypertension

Arterial baroreflex sensitivity, plasma norepinephrine (NE) and epinephrine (E), and pressor and depressor responses were assessed in 25 patients with essential hypertension and 29 normotensive control subjects. Sensitivity of the cardiac limb of the baroreflex was determined by blood pressure and interbeat interval responses associated with the Valsalva maneuver, externally applied neck suction and pressure, and injection of phenylephrine and nitroglycerin. By all these techniques, patients with essential hypertension had significantly decreased baroreflex sensitivity, even after adjustment for age mismatching between the hypertensive and normotensive groups. Hypertensive patients also had significantly higher mean levels of plasma NE and E in both brachial arterial and antecubital venous blood (246 vs 154 pg/ml arterial NE, 286 vs 184 pg/ml venous NE, 99 vs 55 pg/ml arterial E, and 65 vs 35 pg/ml venous E) and significantly larger pressor responses to injected phenylephrine (30.9 mm Hg/100 micrograms vs 16.7 mm Hg/100 micrograms). When baroreflex-cardiac sensitivity values measured by the various techniques were averaged, there was a significant inverse relationship between sensitivity and venous NE and between sensitivity and pressor responsiveness. The results indicate that decreased baroreflex-cardiac sensitivity, increased sympathetic outflow, and pressor hyperresponsiveness tend to occur together in some patients with essential hypertension. Decreased arterial distensibility and altered central neural integration can account for these findings.     

Reduced baroreflex changes in muscle sympathetic nerve activity during blood pressure elevation in essential hypertension.

To determine whether the baroreflex control of sympathetic nerve activity is altered in patients with essential hypertension, muscle sympathetic nerve activity (MSNA) was recorded microneurographically from the tibial nerves of 23 normotensive subjects and 23 patients with essential hypertension. When phenylephrine (2 micrograms/kg) was injected intravenously, although the pressor response of mean arterial blood pressure (MAP) was significantly enhanced in the hypertensives as compared with the normotensives, the reflex decrease in MSNA was significantly smaller in the hypertensives. Furthermore, the baroreflex slope for MSNA, used as an index of baroreflex sensitivity and calculated by relating the change in MSNA to the change in MAP, was significantly less in the hypertensives. Following the injection of nitroglycerin (2 micrograms/kg), there were no significant differences between the normotensives and hypertensives in the depressor response, the reflex increase in MSNA or the baroreflex slope for MSNA. These observations suggest that the baroreflex change in sympathetic nerve activity is reduced during phenylephrine-induced blood pressure elevation but not during nitroglycerin-induced hypotension in the hypertensives, and that the blunted response of sympathetic nerve activity occurring during hypertension in these hypertensive patients may underlie the maintenance of high blood pressure in essential hypertension.     

Functional interaction between nucleus tractus solitarius NK1 and 5-HT3 receptors in the inhibition of baroreflex in rats

OBJECTIVE: Previous data showed that in the nucleus tractus solitarius (NTS), 5-HT(3) receptors are critically involved in the inhibition of cardiac baroreceptor reflex response occurring during the defense reaction. Since stimulation of NTS NK(1) receptors has been found to inhibit the baroreflex bradycardia, we examined in this study whether this reflex response is inhibited during the defense reaction via an interaction between NK(1) and 5-HT(3) receptors. METHODS: For this purpose, we analyzed in urethane-anaesthetized rats the effects of intra-NTS GR205171, a selective NK(1) receptor antagonist, on the baroreflex bradycardia inhibition observed either during the defense reaction triggered by electrical stimulation of the dorsal periaqueductal grey matter (dPAG) or after NTS 5-HT(3) receptor activation. RESULTS: Intra-NTS GR205171, reversed, in dose-dependent manner, the inhibitory effect of dPAG stimulation on baroreflex bradycardia. This reversion was of 49% when both sinus carotid and aortic baroreceptors were stimulated by phenylephrine, and of 84% when aortic depressor nerve was stimulated. Similarly, intra-NTS GR205171 reversed partially or almost totally the inhibitory effect of local microinjections of phenylbiguanide, a 5-HT(3) receptor agonist, on baroreflex bradycardia induced either by phenylephrine administration or aortic nerve stimulation, respectively. CONCLUSION: These results strongly suggest that NK(1) receptors contribute downstream to the 5-HT(3) receptor-mediated inhibition of the aortic but not carotid cardiac baroreflex response occurring during the defense reaction, therefore implying that baroreceptor afferent inputs may be differentially modulated depending on their origin. This differentiation may be useful for a better understanding of baroreflex dysfunction in disease-induced conditions.     

Central Mechanisms in Doc-Salt Hypertensive Rats

These experiments were intended to elucidate the role of central mechanisms in the maintenance of high blood pressure produced by deoxycorticosterone (DOC) and salt in rats. We investigated the central effect of angiotensin (AII) on systemic arterial blood pressure and plasma arginine vasopressin (AVP) in DOC-salt and control rats. There was a pronounced augmentation of the pressor responsiveness to centrally injected AII in DOC-salt hypertensive rats; but there was no difference in AII induced AVP release in DOC-salt hypertensive rats compared to sham controls. The increase in vascular resistance of the perfused hindquarters induced by stimulation of the lumbar sympathetic chains did not change in DOC-salt hypertensive rats although the increases induced by norepinephrine (NE) were potentiated at the higher doses. Pressor responsiveness of the DOC-salt hypertensive rats to i.v. administration of AII, AVP and NE was shown to be augmented by factors of 3.6, 2.5 and 1.8 respectively in DOC-salt rats. Reflex bradycardia to these pressor responses was attenuated indicating impairment of baroreflex function. The potentiation of pressor responses to centrally injected AII in DOC-salt hypertensive rats was greater than could be explained by augmented pressor responsiveness to iv NE and AVP. Neither baroreflex dysfunction, facilitated release of NE at sympathetic terminals, nor augmented release of AVP into the circulation could explain the potentiation. Therefore, our data suggested that selective central amplification of sympathetic vasomotor responses to centrally injected AII stimuli may play a role in the hypertension after 3 weeks of DOC-salt treatment in rats.     

Modulatory effects of carbon monoxide on baroreflex activation in nucleus tractus solitarii of rats

Recent studies suggest that carbon monoxide (CO), which is produced in significant quantities in many brain regions, may function as a neurotransmitter. Heme oxygenase catalyzes the metabolism of heme to CO and biliverdin; however, the physiological role of CO in central cardiovascular regulation was not well understood. In the present study, we evaluated the baroreflex response of CO in the nucleus tractus solitarii (NTS) of rats. Male Sprague-Dawley rats were anesthetized with urethane, and blood pressure and heart rate were monitored intra-arterially. Unilateral microinjection (60 nL) of hematin, a heme molecule cleaved by heme oxygenase to yield CO, into the NTS produced prominent dose-related depressor and bradycardic effects. Baroreflex responses were elicited by increasing doses of phenylephrine (10 to 30 microg/kg IV) before and after intra-NTS administration of zinc deuteroporphyrin 2,4-bis-glycol (ZnDPBG) (1 nmol), an inhibitor of heme oxygenase activity, or vehicle alone. The reflex bradycardia elicited by phenylephrine was significantly inhibited by pretreatment with ZnDPBG. Furthermore, the inhibitory effect of ZnDPBG on baroreflex activation was dose dependent. These results suggest CO formed by brain heme oxygenase plays a significant role in central cardiovascular regulation and that inhibition of heme oxygenase attenuated baroreflex activation.     

Altered Cardiovascular Responses to Glutamate and Acetylcholine Microinjected into the Nucleus Tractus Solitarii of the SHR

L-glutamate (GLU) or acetylcholine (ACh) injected into the nucleus tractus solitarii (NTS) of rat elicits a decrease in arterial pressure (AP) and heart rate (HR) similar to that seen with activation of the baroreflex. Both compounds may play a role in the mediation of the baroreflex at the level of NTS. The baroreflex may be disturbed in the spontaneously hypertensive rat (SHR). Thus we sought to determine if the dose-related responses to microin-jection (50 nl) of the two putative transmitters into NTS may be altered in     

Effects of insulin on pressor responsiveness and baroreflex function in diabetes mellitus

The effects of insulin on pressor responsiveness to alpha agonist (phenylephrine) and angiotensin II, and baroreflex function were studied in fifteen diabetic patients without autonomic neuropathy. The dose of phenylephrine required to increase systolic pressure by 25 mmHg (PD25) was significantly increased from 38 +/- 7 to 62 +/- 9 micrograms (p less than 0.05) after IV injection of 4 U of Actrapid monocomponent insulin. The dose of angiotensin II required to increase systolic pressure by 30 mmHg (AD30) was also increased from 0.29 +/- 0.07 to 0.48 +/- 0.10 micrograms (p less than 0.01). Following insulin administration, the dose-response curves for phenylephrine and angiotensin II were shifted to the right. The baroreflex sensitivity was not affected by insulin. In contrast, there was no significant change in PD25, AD30 or baroreflex sensitivity after the injection of saline. These results suggest that insulin attenuates the pressor responsiveness to alpha agonist and angiotensin II, which may be one of the significant mechanisms in insulin-induced vasodilation.