神经肽Y和去甲肾上腺素在杏仁内侧核内影响血压和心率中…

分别向杏仁内侧核（ＭＡＮ）内微量注射去甲肾上腺素（ＮＡ）或神经肽Ｙ（ＮＰＹ）。ＮＡ引起血压长高,心率加快;而ＮＰＹ引起血压降低,心率减慢。如果注入不能改变血压的小剂量ＮＰＹ,则可抑制ＮＡ引起的升压作用,反映ＮＰＹ与ＮＡ共同参与心血管活动的中枢性调节过程。向ＭＡＮ中注射ＮＰＹ后血中ＮＡ的含量也相应降低,表明在ＭＡＮ中注射ＮＰＹ引起的血压、心率反应是通过降低血浆中ＮＡ含量而实现的。     

延髓腹外侧区微量注射L－NNA和SNP对大鼠血压、心率和肾交感神经活动的影响

在麻醉大鼠观察了向延髓腹外侧区微量注射ＮＯ合成酶抑制剂Ｎ－硝基左旋精氨酸（ＬＮＮＡ）和硝普钢（ＳＮＰ）对血压、心率和肾交感神经活动的影响,旨在探讨中枢左旋精氨酸－ＮＯ通路在动脉血压调节中的作用及其机制。实验结果如下：（１）向延髓腹外侧头端区（ＲＶＬＭ）注射Ｌ－ＮＮＡ后,平均动脉压（ＭＡＰ）升高,肾交感神经活动（ＲＳＮＡ）增强;心率（ＨＲ）减慢,但无统计学意义。ＭＡＰ和ＲＳＮＡ的变化持续３０ｍｉｎ以上;此效应可被预先静注左旋精氨酸所逆转。（２）向ＲＶＬＭ微量注射ＳＮＰ,ＭＡＰ降低,ＲＳＮＡ减弱;但ＨＲ的变化无统计学意义。（３）向延髓腹外侧尾端区（ＣＶＬＭ）注射Ｌ－ＮＮＡ,ＭＡＰ降低,ＨＲ减慢,ＲＳＮＡ减弱。（４）向ＣＶＬＭ微量注射ＳＮＰ,ＭＡＰ升高,ＲＳＮＡ增强,而心率无明显变化。以上结果表明,中枢左旋精氨酸－ＮＯ通路对延髓腹外侧部的神经元活动有调变作用。     

L－NNA及NO供体对延髓腹外侧头端区神经元自发放电的影响

在麻醉大鼠观察了静注ＮＯ合成酶抑制剂Ｎ－硝基左旋精氨酸（Ｌ－ＮＮＡ）和ＮＯ供体──硝普钠（ＳＮＰ）和ＳＩＮ－Ｉ对血压、心率和延髓腹外侧头端区（ＲＶＬＭ）神经元自发放电活动的影响,旨在探讨Ｌ－ａｒｇ：ＮＯ通路对动脉血压调节的中枢作用部位。所得结果如下：（１）静注Ｌ－ＮＮＡ后,平均动脉压（ＭＡＰ）升高,心率（ＨＲ）加快,１１个ＲＶＬＭ神经元自发放电频率增加。这些变化发生于给药后５ｍｉｎ,持续时间达３０ｍｉｎ以上。（２）静注ＳＮＰ后,ＭＡＰ降低,ＨＲ加快,２３个ＲＶＬＭ神经元自发放电频率降低,且有剂量依赖性。ＳＮＰ作用发生快,持续时间短。为了排除脑缺血的影响,还特意向一侧颈动脉内注射相同剂量ＳＮＰ,结果引起ＭＡＰ轻度降低,而ＨＲ无明显改变,但ＲＶＬＭ神经元自发放电频率仍显著降低。（３）静注另一ＮＯ供体ＳＩＮ－Ｉ后,ＭＡＰ降低,１１个ＲＶＬＭ神经元自发放电频率降低．与ＳＮＰ的效应基本一致。以上结果提示,ＲＶＬＭ是Ｌ－ａｒｇ：ＮＯ通路实现动脉血压调节的一个中枢作用部位。     

孤束核内注NPY抗体对电刺激室旁核引起心血管反应的影响

本实验在乌拉坦麻醉的大鼠上进行。电刺激下丘脑室旁核（ＰＶＨ）使动脉血压升高,心率加快,并伴有瞳孔扩大,胡须抖动等交感反应。向孤束核（ＮＴＳ）微量注射神经肽Ｙ（ＮＰＹ）抗体后,电刺激ＰＶＨ引起的升压反应被阻断５３．８％,心率加快被阻断５７．１％,交感反应也被减弱。兴奋缰核（Ｈｂ）可对抗孤束核内注射ＮＰＹ抗体对室旁核引起的心血管反应的影响。结果提示：孤束核参与电刺激ＰＶＨ引起的心血管作用,其间有ＮＰＹ纤维的参与,同时证明Ｈｂ在其中起一定的作用。     

糖皮质激素在孤束核内对去甲肾上腺素/神经肽Y引起的心血管效应的影响及其机制

本研究观察了糖皮质激素自身在孤束核（ＮＴＳ）内的心血管效应,以及它在ＮＴＳ内对ＮＡＮＰＹ诱导的心血管活动变化的影响及机制。结果发现,大剂量地塞米松（Ｄｅｘ）在大鼠ＮＴＳ内能很快导致血压下降,血清中ＮＯ浓度升高。小剂量Ｄｅｘ在ＮＴＳ内能很快抑制ＮＡＮＰＹ在ＮＴＳ内诱导的心血管效应,并维持较长时间。表明Ｄｅｘ对ＮＡＮＰＹ在ＮＴＳ诱导的心血管效应的抑制作用可能有基因和非基因两种途径参与。进一步分析它的非基因机制发现这种快速抑制作用与胞内糖皮质激素受体无关,而是通过兴奋ＧＡＢＡＡ受体,降低减压反射;或者降低α２受体的敏感性,抑制ＮＯ的形成;或者直接作用于细胞膜上的离子通道以影响它们对ＮＡＮＰＹ的反应;从而抑制ＮＡＮＰＹ在ＮＴＳ内诱导的降压和心率减慢的效应     

选择性切除交感神经对大鼠心内神经节中去甲肾上腺素、乙酰胆碱和NPY的影响

为了探讨心内神经节中去甲肾上腺素（ＮＡ）、乙酰胆碱（ＡＣｈ）和ＮＰＹ的相互作用,本实验应用６－ＯＨ－ＤＡ选择性切除大鼠心脏交感神经纤维,然后应用荧光和酶组织化学法、免疫组织化学结合图像分析法观察了大鼠心内神经节ＮＡ、ＡＣｈＥ活性和ＮＰＹ的变化。结果显示：实验组大鼠心内神经节中儿茶酚胺荧光反应阳性和ＮＰＹ免疫反应（ＮＰＹ－ＩＲ）阳性的神经纤维明显减少,ＡＣｈＥ阳性神经纤维明显增多,ＡＣｈＥ反应性神经元积分光密度增加,而儿茶酚胺荧光反应和ＮＰＹ－ＩＲ阳性神经元变化不明显。结果提示：１．交感神经化学切除后大鼠心内神经节中ＮＡ、ＡＣｈＥ活性和ＮＰＹ出现不同的变化,体现了心脏交感神经和副交感神经的相互抑制作用;２．心内神经节可能含有两种性质的ＮＰＹ,即交感性和非交感性ＮＰＹ。     

中缝大核在刺激视上核镇痛中的作用

运用核团灌流液的放免测定和高压液相色谱法以及核团内注射拮抗剂,观察了化学刺激下丘脑视上核（ＳＯＮ）对中缝大核（ＮＲＭ）灌流液内催产素（ＯＴ）、精氨酸加压素（ＡＶＰ）和５－羟色胺（５－ＨＴ）含量的影响以及ＮＲＭ内注射ＡＶＰ、５－ＨＴ或ＯＴ受体拮抗剂对痛阈（ＰＴ）的影响。结果表明：ＳＯＮ内注射Ｌ－谷氨酸（Ｌ－Ｇｌｕ）１０μｇ后动物痛阈明显升高,ＮＲＭ灌流液中ＯＴ和５－ＨＴ的含量明显高于对照组水平,ＡＶＰ的含量仅有一过性增加。ＮＲＭ内注射ｏＴ或５－ＨＴ拮抗剂可逆转化学刺激ＳＯＮ引起的镇痛作用;而ＡＶＰ的Ｖ＿(１／２)受体拮抗剂也轻度抑制这种镇痛作用,但Ｖ＿１拮抗剂对此作用无影响。以上结果提示：在刺激ＳＯＮ镇痛中,ＯＴ起着重要作用,Ｌ－Ｇｌｕ刺激ＳＯＮ的ＯＴ细胞释放ＯＴ,作用于ＮＲＭ细胞的ＯＴ受体和Ｖ＿２受体而产生镇痛作用,５－ＨＴ在此过程中也发挥重要作用。     

地塞米松对大鼠孤束核压力感受性神经元微电泳NA/NPY所致反应的影响

实验采用多管微电泳记录神经元胞外放电技术,观察地塞米松（Ｄｅｘ）、去甲肾上腺素（ＮＡ）及神经肽Ｙ（ＮＰＹ）对孤束核（ＮＴＳ）压力感受反射性神经元的作用,以及将这些神经元用Ｄｅｘ预处理后对ＮＡ／ＮＰＹ反应的变化。向ＮＴＳ内３８个压力感受神经元微电泳Ｄｅｘ后,压力感受兴奋性神经元主要表现为抑制（８／１９）,压力感受抑制性神经元则主要表现为兴奋（９／１９）。而电泳ＮＡ或ＮＰＹ,压力感受兴奋性神经性元以兴     

侧脑室注射一叶萩碱的心血管效应及作用机制

在麻醉大鼠侧脑室注射左旋一叶Ｑｉｕ碱（Ｌ－Ｓｅｃ）,记录动脉血压（ＡＰ）、心率（ＨＲ）及肾交感神经放电（ＲＳＮＤ）,观察前脑室周系统ＧＡＢＡ能紧张性活动改变引起的心血管效应。结果如下：（１）Ｌ－Ｓｅｃ可引起ＲＳＮＤ增加、ＡＰ升高和ＨＲ加快,并呈一定剂量－效应关系;但Ｌ－Ｓ盈余 于ｂｉｃｕｃｕｌｌｉｎｅ（Ｂｉｃ）。（２）Ｌ－Ｓｅｃ既能拮抗ｍｕｓｃｉｍｏｌ（Ｍｕｓ）,又能拮抗ｂａｃｌｏｆｅｎ（Ｂａｃ）     

内源性一氧化氮在高血压心肌肥厚中的作用

目的和方法：本实验用Ｌ精氨酸和一氧化氮合酶（ＮＯＳ）抑制剂ＬＮＡＭＥ观察内源性一氧化氮（ＮＯ）在高血压性心肌肥厚中的作用。结果：腹主动脉缩窄引起大鼠动脉血压显著升高,左心室重量／体重比值显著增加,左心室ＮＯ含量显著下降;Ｌ精氨酸不影响主动脉缩窄大鼠动脉血压,但减轻左心室重量／体重比值,明显升高左心室ＮＯ含量,加入ＬＮＡＭＥ可消除Ｌ精氨酸的上述作用;主动脉缩窄大鼠给予ＬＮＡＭＥ,动脉血压和左心室／体重比值并没有进一步增加;假手术大鼠给予ＬＮＡＭＥ,血压明显升高,左心室重量／体重比值轻度增加;主动脉缩窄大鼠不论是服用Ｌ精氨酸还是ＬＮＡＭＥ,左心室ｃＧＭＰ含量都明显增加。结论：口服Ｌ精氨酸可减轻主动脉缩窄大鼠心肌肥厚但不影响动脉血压,此作用可能是通过Ｌ精氨酸ＮＯ途径实现的,与ｃＧＭＰ机制无关。     

糖皮质激素在孤束核内去甲肾上腺素／神经肽Y引起的心血管效应的影响及其机

本研究观察了糖皮质激素自身在孤束核ＮＴＳ内的心血管效应,以及它在ＮＴＳ内对ＮＡ／ＮＰＹ诱导的心血管活动变化的影响及机制。结果发现,大剂量地塞米松在大鼠ＮＴＳ的内能很快导致血压下降,血清中ＮＯ浓度升高。小剂量Ｄｅｘ在ＮＴＳ内能很快抑制ＮＡ／ＮＰＹ在ＮＴＳ内诱导的心血管效应,并维持较长时间。表明Ｄｅｘ对ＮＡ／ＮＰＹ在ＮＴＳ诱导的心血管效应,并维持较长时间。表明Ｄｅｘ对ＮＡ／ＮＰＹ在ＮＴＳ诱导的心血管效     

Cardiovascular effects of neuropeptide Y in the nucleus tractus solitarius of rats: relationship with noradrenaline and vasopressin

The central haemodynamic effects of neuropeptide Y (NPY), both alone and together with either noradrenaline (NA) or vasopressin (AVP), have been investigated by microinjecting synthetic peptide into the nucleus tractus solitarius (NTS) of anaesthetized rats. NPY alone elicited dose-dependent changes in blood pressure (BP) and heart rate (HR); 470 fmol inducing a pressor response, and 4.7 pmol a fall in BP. The hypotensive response to 20 nmol NA was significantly modified by both simultaneous and prior injection of an ineffective dose (47 fmol) of NPY. Prior injection of a similar dose of NPY also modified the NTS pressor effect of 10 ng AVP. A relationship between the action of AVP and NPY in the NTS was further indicated by the finding that prior injection of an ineffective dose of AVP (1 ng) reduced the hypotensive response to 4.7 pmol NPY, and by the demonstration of contrasting effects of 4.7 pmol NPY in AVP-deficient Brattleboro rats compared to parent strain LE rats. These results, taken together with the recent localization of NPY-like immunoreactivity in the NTS, suggest a role for NPY in central cardiovascular control. In addition, NPY has been shown to exhibit functional interactions with both an amine neurotransmitter and a neuropeptide present in the NTS of rats.     

Vasoconstrictor effects in vivo and plasma disappearance rate of neuropeptide Y in man

Vascular effects of neuropeptide Y (NPY) and noradrenaline (NA) were studied in six human volunteers. Systemic infusion of human NPY for 40 min (5 pmol X kg-1 X min-1) increased arterial plasma NPY-like immunoreactivity (NPY-LI) from 12 +/- 2 to 356 +/- 30 pM. This concentration caused no systemic cardiovascular effects. The disappearance curve for NPY-LI was biphasic; the slopes of the two phases corresponding to half lives of 4.1 +/- 0.4 and 20 +/- 2 min respectively. Close i.a. infusion of human NPY in the forearm caused a slowly developing and dose dependent decrease in forearm blood flow (FBF) and increase in venous tone with maximal values of 44 +/- 6 and 235 +/- 81% of control respectively at 5 nmol X min-1. The corresponding values for NA (5 nmol X min-1) were 21 +/- 9 and 489 +/- 78% of control. A threshold concentration for a decrease in FBF was obtained at a plasma NPY-LI of 3.7 +/- 0.6 nM. The decrease in FBF caused by NPY was maintained for a much longer period compared to that of NA.     

Increased plasma levels of neuropeptide Y-like immunoreactivity and catecholamines in severe hypertension remain after treatment to normotension in man

Circulating levels of neuropeptide Y (NPY)-like immunoreactivity (-LI), adrenaline and noradrenaline (NA) were analysed in 17 patients admitted to the emergency ward due to severe hypertension; blood pressure mean 204/127 mmHg. The levels of NPY-LI and NA were significantly higher (P less than 0.001) in the hypertensives as compared to a normotensive control group. HPLC analysis revealed that the plasma contained besides NPY-LI also several NPY-LI fragments of low hydrophobicity. Following 2 to 3 weeks treatment the blood pressure had decreased to a mean of 150/89 mmHg. However, circulating levels of NPY-LI (P less than 0.001) and NA (P less than 0.01) were still significantly higher than in controls in spite of the marked reduction in blood pressure. Simultaneous measurements of adrenaline did not reveal any significant changes and these values did not differ compared with those in the normotensive subjects. The findings suggest that peripheral markers of the sympathetic system (NPY-LI and NA) in severe hypertension is not directly related to the blood pressure level.     

Stress-induced changes of circulating neuropeptide Y in the rat: comparison with catecholamines

Circulating concentrations of neuropeptide Y-like immunoreactivity (NPY), noradrenaline (NA) and adrenaline (AD) were measured in conscious, chronically catheterized rats submitted to various stress protocols. Basal plasma levels of NPY, NA and AD (194 +/- 52 fmol/ml, 0.90 +/- 0.11 pmol/ml and 0.52 +/- 0.07 pmol/ml) were increased by handling (+132%, +76% and +629%, respectively) and rose further during electric shock treatment. Adrenalectomy resulted in the complete disappearance of circulating adrenaline but did not alter either control or stress values of noradrenaline. In comparison circulating levels of NPY were reduced, but not significantly in adrenalectomized animals. Insulin stress induced a large increase in plasma AD levels and cold stress induced an increase in plasma NA levels, without any parallel change in NPY concentrations. These results demonstrate that NPY, which is colocalized with catecholamines in the peripheral nervous systems, is also released during stress responses and that its release parallels more closely changes in circulating NA than AD. Furthermore, stress-induced changes in circulating NPY-like immunoreactivity do not originate from the adrenal gland but mainly from the peripheral nervous system, and the release of NPY is dependent upon the nature of the stimulus.     

Central neuropeptide Y induces proximal stomach relaxation via Y1 receptors in the dorsal vagal complex of the rat

Effects of neuropeptide Y (NPY) on motility of the proximal stomach was examined in anesthetized rats. Intragastric pressure was measured using a balloon situated in the proximal part of the stomach. Administration of NPY into the fourth ventricle induced relaxation of the proximal stomach in a dose-dependent manner. Administration of an Y1 receptor (Y1R) agonist [Leu31, Pro34]NPY induced a larger relaxation than NPY. The administration of an Y2 receptor agonist (NPY 13-36) did not induce significant changes in motility. Microinjections of [Leu31, Pro34]NPY into the caudal part of the dorsal vagal complex (DVC) induced relaxation of the proximal stomach. In contrast, similar injections into the intermediate part of the DVC increased IGP of the proximal stomach. Administration of NPY into the fourth ventricle did not induce relaxation after bilateral injections of the Y1R antagonist (1229U91) into the caudal DVC. These results indicate that NPY induces relaxation in the proximal stomach via Y1Rs situated in the DVC. Because bilateral vagotomy below the diaphragm abolished the relaxation induced by the administration of NPY into the fourth ventricle, relaxation induced by NPY is probably mediated by vagal preganglionic neurons. Intravenous injection of atropine methyl nitrate reduced relaxation induced by administration of NPY. Therefore, relaxation induced by NPY is likely mediated by peripheral cholinergic neurons.     

Neuropeptide Y and peptide YY mediate nonadrenergic vasoconstriction and modulate sympathetic responses in rats

The modulation of cardiovascular sympathetic responses by neuropeptide Y (NPY) and peptide YY (PYY) was assessed in vivo, in pithed rats. Both peptides (0.02-2 nmol/kg) caused similar dose-dependent pressor responses, resistant to adrenergic blockade but antagonized by the calcium channel blocker, nifedipine. Only NPY, at the lowest dose, slightly accelerated heart rate (by 10 +/- 4 beats/min). At the pressor dose (0.6 nmol/kg) but not subpressor dose (0.2 nmol/kg), the increase in blood pressure induced by stimulation of the sympathetic outflow (ST: 0.3 Hz, 50 V, 1 min) was attenuated by PYY (by 40%), whereas ST-evoked tachycardia was reduced by NPY (by 35%). Neither NPY- nor PYY-pretreatment affected ST-induced increments in plasma norepinephrine (NE) and epinephrine concentrations. In addition, regional hemodynamic effects of NPY were studied in conscious rats instrumented with Doppler flow probes. The hypertension caused by NPY was attended by reflex bradycardia and marked rise in peripheral vascular resistance in renal (+ 233 +/- 59%), superior mesenteric (+ 183 +/- 65%) and hindquarter (+ 65 +/- 10%) circulation. The pattern of hemodynamic responses of NPY was similar to that of NE but, unlike the latter, persisted after adrenergic blockade.     

Differential cardiovascular effects mediated by mu and kappa opiate receptors in hindbrain nuclei

To further investigate the role of opioid peptides and specific opiate receptor subtypes in central cardiovascular regulation by hindbrain nuclei, mu (D-Ala²,MePhe⁴,Gly-ol⁵ enkephalin, DAGO), delta (D-Ala²,D-Leu⁵ enkephalin, DADL) or kappa (MRZ 2549) agonists were microinjected into hindbrain nuclei of spontaneously or artificially respired, pentobarbital-anesthetized rats. In the nucleus tractus solitarius (NTS), DAGO and DADL (0.3 nmol) elicited pressor responses and tachycardia. MRZ (3.0–16 nmol) depressed blood pressure in spontaneously breathing rats, but accelerated heart rate in artificially ventilated animals. Blood pressure and heart rate of spontaneously breathing animals were not altered following nucleus ambiguus (NA) injection of DAGO or DADL (0.3 nmol), but were elevated in artificially respired animals; MRZ (3.0–10 nmol) injected into the NA depressed blood pressure in both groups. These data suggest that in the absence of respiratory depression, NTS and NA mu receptors mediate pressor responses and tachycardia; kappa receptors in the NA mediate a decrease in blood pressure but cardioacceleration in the NTS.     

Cardiac function in neuropeptide Y Y4 receptor-knockout mice

Autonomic control of cardiovascular function in neuropeptide Y (NPY) Y4 receptor-knockout mice was investigated using pancreatic polypeptide (PP), NPY and specific agonists and antagonists for other NPY receptors well characterised in cardiovascular function. Y4 receptor-knockout mice, anaesthetised with sodium pentobarbitone, displayed slower heart rate, indicated by a higher pulse interval and lower blood pressure compared to control mice. After vagus nerves were cut heart rate increased but was still significantly slower than in control mice. PP had no effect on blood pressure or cardiac vagal activity in either group of mice, which was consistent with earlier studies in other species. Injection of NPY evoked an increase in blood pressure but the response was significantly reduced in Y4 receptor-knockout mice compared to the controls. The reduction in pressor activity was not Y1 mediated as the selective Y1 antagonist, BIBP 3226, was effective in blocking NPY pressor activity in knockout mice. In addition, cardiac vagal inhibitory activity evoked by low doses of NPY was also reduced when compared to control responses. As N-acetyl [Leu(28, 31)] NPY 24-36 inhibited vagal activity dose dependently in both groups of mice with no difference in response at any dose, it is unlikely that this effect also is receptor mediated. We propose that the reduced vasoconstrictor and vagal inhibitory activity evoked by NPY in Y4 receptor-knockout mice is due to a lack of adrenergic tone bought about by a proposed reduction in sympathetic activity, possibly resulting from altered NPY activity secondarily affecting adrenergic transmission. We conclude that Y4 receptor deletion disrupts autonomic balance within the cardiovascular system.