大鼠脑室内注射氨甲酰胆碱对肾钠,钾,水排出的影响

在麻醉大鼠侧脑室注射胆碱能激动剂氨甲酰胆碱（ＣＢＣ）引起显著的促钠排泄、促钾排泄和利尿反应（Ｐ＜０．０５）,其中促钠排泄反应与剂量之间呈量效关系（ｒ＝０．９９９７,Ｐ＜０．０５）。由脑室注射ＣＢＣ（２．７４×１０－３μｍｏｌ）引起的上述反应可以被胆碱能Ｍ受体阻断剂阿托品或Ｎ受体阻断剂六甲双胺预处理完全阻断（Ｐ＜０．０５）。同样,ＣＢＣ的肾脏效应也可被肾上腺素能α受体阻断剂酚妥拉明预处理所部分阻断（Ｐ＜０．０５）。上述结果表明脑室注射ＣＢＣ引起的促钠排泄、促钾排泄和利尿反应是刺激了脑胆碱能Ｍ或Ｎ受体,有部分效应可能继发刺激去甲肾上腺素能α受体。     

兔脊髓α受体对血量扩张引起肾交感神经活动抑制和促钠排泄的作用

在窦主动脉去神经麻醉兔观察阻断脊髓α受体对血量扩张引起肾交感神经活动（RSNA）抑制和促钠排泄反应的影响。兔脊髓蛛网膜下腔注射a肾上腺素能受体阻断剂酚妥拉明与人工脑脊液后,血量扩张引起RSNA抑制分别为（－25．4±5．4）％与（－42．5±5.2）％（P＜0.05）;兔脊髓蛛网膜下腔注射α1受体阻断剂哌唑嗪与人工脑脊液后血量扩张引起RSNA抑制分别为（－29．3±6.1）％与（－42．5±5.2）％（P＜005）。结果表明,阻断脊髓α受体或α1受体均可减弱血量扩张引起RSNA抑制。脊髓注射哌唑嗪后血量扩张引起促钠排泄与利尿反应也显著减弱（P＜005）。     

脑胆碱能刺激引起的促钠排泄反应和肾的ChAT-IR的变化

目的：观察肾胆碱能系统在大鼠侧脑室注射胆碱能激动剂氨甲酰胆碱（CBC）诱导的促钠排泄反应中的作用。方法：通过整体实验和免疫组化的方法观察大鼠侧脑室注射CBC 0.5μg后,肾排纳量的变化和肾的但碱乙酰转移酶（ChAT）免疫反应活性的变化;阿托品（30μg）阻断脑胆碱能M受体后,对上述效应的影响。结果：侧脑室给予CBC后40min,肾排钠量显著增加,肾近曲小管ChAT-IR显著增强（P〈0．05）;阿托品阻断后,上述反应显著减弱（P〈0．05）。结论：肾小管上皮细胞的胆碱能系统可能参与脑胆碱能刺激引起的肾促钠排泄反应。     

肾神经在扩张心房时对尿量和尿钠排出的作用

单侧肾去神经的麻醉狗,用乳胶小囊扩张肺静脉-心房连接部,观察到神经完好肾的尿流量与排钠量均显著增加(P<0.01);去神经肾的尿流量仍显著增加(P<0 01),但排钠量无明显变化(P>0.05);两侧肾的肾小球滤过率(GFR)及肾血浆流量(RPF)均保持稳定;神经完好肾的静脉血浆肾素活性(PRA)及血管紧张素Ⅱ水平(PAⅡ)均明显降低,PAⅡ降低的幅度与尿流量增加的幅度无相关(r=-0.2975,P>0.05);与排钠量增加的幅度也无相关(r=-0.2359,P>0.05);去神经肾的PRA和PAⅡ都没有显著变化。说明在刺激心房感受器引起的利尿与尿钠排泄的反应中,肾神经主要促进肾对尿钠的排出。肾神经的这种作用既不是通过改变GFR和RPF,也不是抑制肾素的释放,而可能是由于直接影响肾小管对钠的重吸收。     

脑室注射强啡肽A—（1—13）对肾水钠钾排出的影响及其机制

实验在１２％乙醇麻醉大鼠进行,侧脑室注射强啡肽Ａ－（１－１３）（ＤＹＮ）观察对肾水钠钾排出的影响。注射ＤＹＮ１０μｇ可使大鼠尿量明显增加,尿钠,尿钾浓度降低,但排钠量,排钾量无明显变化。注药后２０ｍｉｎ尿量开始增加,持续１２０ｍｉｎ。侧脑室预先注射纳洛酮（ＮＸ２０μｇ／μｌ）或阿托品（Ａｔｒ１０μｇ／μｌ）均可阻断ＤＹＮ的利尿效应。     

兔室旁核对血量扩张引起促钠排泄与利尿的作用

在室旁核(PVN)假损毁兔与PVN损毁兔血量扩张(VE)引起尿流量增加,峰值分别为0.59±0.09与0.31±0.03 ml/min (P<0.01),排钠量增加峰值分别为66.76±6.74与36.05±3.44μmol/min (P<0.01),而在PVN假损毁兔与PVN完好兔对VE的反应无显著差别(P>0.05),表明PVN损伤可明显减弱 VE 引起的促钠排泄与利尿效应.颈迷走神经切断并不能改变 PVN损伤的上述作用.双侧肾神经切断兔损毁 PVN对VE引起促钠排泄效应无显著影响,但显著减弱其利尿效应 (P<0.02).PVN损毁对VE时肾小球滤过率(GFR)与肾血浆流量(RPF)无显著影响.结果表明PVN参与VE通过迷走传入神经引起促钠排泄与利尿反应的调节,而肾交感传出神经参与其中促钠排泄的作用.     

脑胆碱能刺激引起的促钠排泄反应和蓝斑ChAT-IR的变化

目的：观察大鼠侧脑室注射胆碱能激动剂氨甲酰胆碱（CBC）后蓝斑胆碱能神经元活性变化及其与促钠排泄反应的关系。方法：选用SD雄性大鼠通过整体实验和免疫组化方法,观察侧脑室给予氨甲酰胆碱（0．5μg）和俄阿托品（30μg）后肾排钠量的变化及蓝斑胆碱乙酰转移酶（CHAT）免疫反应活性的变化。结果：侧脑室给予氨甲酰胆碱后40min,肾排钠量显著增加,蓝斑的CHAT-IR明显增强（P〈0．05）;阿托品预处理后可明显抑制上述反应。结论：蓝斑的胆碱能神经元参与侧脑室注射氨甲酰胆碱引起的促钠排泄反应。     

雨蛙肽中枢促胃酸分泌作用机制的初步分析

利用特异的受体阻断剂能够拮抗相应的受体激动剂的效应的原理,分析雨蛙肽中枢促胃酸分泌作用的受体机制。向大鼠侧脑室内注射微量雨蛙肽(67ng/鼠),可引起急性灌流大鼠胃酸分泌明显增加。预先向大鼠侧脑室内注射肾上腺素受体阻断剂酚妥拉明或心得安,20min后再向侧脑室内注射雨蛙肽,预处理对雨蛙肽的促胃酸分泌作用影响不大。但事先向侧脑室内注射乙酰胆碱受体阻断剂阿托品或胆囊收缩素(CCK)受体阻断剂二丁酰环化-磷酸鸟苷(Bt_2 cGMP)则可有效地阻断雨蛙肽的作用。以上结果提示,脑内雨蛙肽促胃酸分泌机制中,可能有 CCK 受体和胆碱能受体参与,而与肾上腺素能系统关系不大。     

兔室旁核对血量扩张引起促纳排泄与利尿的作用

在室旁核 (PVN)假损毁兔与PVN损毁兔血量扩张 (VE)引起尿流量增加 ,峰值分别为 0 5 9± 0 0 9与0 3 1± 0 0 3ml/min (P <0 0 1) ,排钠量增加峰值分别为 66 76± 6 74与 3 6 0 5± 3 4 4μmol/min (P <0 0 1) ,而在PVN假损毁兔与PVN完好兔对VE的反应无显著差别 (P >0 0 5 ) ,表明PVN损伤可明显减弱VE引起的促钠排泄与利尿效应。颈迷走神经切断并不能改变PVN损伤的上述作用。双侧肾神经切断兔损毁PVN对VE引起促钠排泄效应无显著影响 ,但显著减弱其利尿效应 (P <0 0 2 )。PVN损毁对VE时肾小球滤过率 (GFR)与肾血浆流量 (RPF)无显著影响。结果表明PVN参与VE通过迷走传入神经引起促钠排泄与利尿反应的调节 ,而肾交感传出神经参与其中促钠排泄的作用     

AT1受体在脑内胆碱能刺激引起的钠水排泄反应中的作用

目的和方法 :本工作通过整体实验和免疫组化的方法 ,观察脑血管紧张素能AT1受体在侧脑室注射氨甲酰胆碱引起的促钠排泄反应中的作用和下丘脑室旁核TH IR的变化。结果 :用脑血管紧张素能AT1受体阻断剂Losar tan( 2 0 μg)预处理 ,可部分阻断侧脑室注射氨甲酰胆碱引起的促钠排泄反应和利尿作用 (P <0 .0 5)。免疫组化实验显示侧脑室给予氨甲酰胆碱后 40min ,下丘脑室旁核 (PVH)、室周核 (Pe)、弓状核 (Arc)和下丘脑前区后部 (AHP)的酪氨酸羟化酶 (TH )免疫反应活性明显增强。Losartan预处理后侧脑室再注射氨甲酰胆碱 ,除PaPo的免疫反应活性未发生明显变化外 ,上述其余神经核团的TH免疫反应活性明显下降。结论 :在脑胆碱能刺激引起的钠水排泄反应中有AT1受体的参与 ;阻断脑血管紧张素能AT1受体对胆碱能刺激引起Arc、Pe和AHP的儿茶酚胺能神经元兴奋性有下调作用。提示脑血管紧张素能和儿茶酚胺能神经通路在下丘脑室旁核等脑区共同参与介导了脑内胆碱能刺激引起的促钠排泄反应 ,同时血管紧张素能神经元还影响儿茶酚胺能神经元的功能活动     

大鼠脑胆碱能系统对血量扩张引起利尿与尿钠排泄...

The role of brain cholinergic system on diuresis and natriuresis induced by volume expansion was studied in conscious rats. In a series of experiments, the diuretic, natriuretic and kaliuretic responses induced by volume expansion were compared in three groups of conscious rats pretreated respectively with intracerebroventricular (icv) injection of artificial cerebrospinal fluid (ACSF), atropine and hexamethonium. The natriuretic, kaliuretic and diuretic responses induced by volume expansion were much less in the animals with icv injection of atropine than in the control group with injection of ACSF (P less than 0.01). While the group pretreated with icv injection of hexamethonium showed no significant decrease in these responses of volume expansion than that of the control (P greater than 0.05). Volume expansion produced no change in insulin and PAH clearance in both the atropine and the ACSF group. Thus the atropine suppressed diuresis, natriuresis and kaliuresis are independent of changes in GFR and RPF. It is inferred from the results of the present investigation that volume expansion induced diuresis and natriuresis appear to be due to inhibition of water and sodium reabsorption in the renal tubules and regulated by certain brain cholinergic system.     

Role of transmitters in mediating hypothalamic control of electrolyte excretion.

Changes in urinary volume and electrolyte excretion were monitored after the injection of cholinergic and monoaminergic drugs into the third cerebral ventricle of conscious male rats made diuretic by an intravenous infusion of 5% dextrose. A natriuretic and kaliuretic response was induced by the intraventricular injection of norephrine (NE) or carbachol, whereas dopamine (DA) had no effect. The beta-receptor stimulator isoproterenol (ISO) induced an antinatriuretic and antikaliuretic effect. Intraventricular injection of the alpha-adrenergic blocker phentolamine abolished the natriuretic response to NE and carbachol and to intraventricular hypertonic saline (HS). By contrast, the beta-adrenergic blocker propranolol induced a natriuresis and kaliuresis when injected alone and an additive effect when its injection was followed by NE or HS. Propranolol potentiated the natriuretic response to carbachol. Cholinergic blockade with atropine diminished the response to NE and blocked the natriuretic response to HS. It is suggested that sodium receptors in the ventricular wall can modify renal sodium excretion via a stimulatory pathway involving cholinergic and alpha-adrenergic receptors and can inhibit sodium excretion via a tonically active beta-receptor pathway.     

Endogenous central kappa-opioid systems augment renal sympathetic nerve activity to maximally retain urinary sodium during hypotonic saline volume expansion

Intracerebroventricular injection of kappa-opioid agonists produces diuresis, antinatriuresis, and a concurrent increase in renal sympathetic nerve activity (RSNA). The present study examined whether endogenous central kappa-opioid systems contribute to the renal excretory responses produced by the stress of an acute hypotonic saline volume expansion (HSVE). Cardiovascular, renal excretory, and RSNA responses were measured during control, acute HSVE (5% body weight, 0.45 M saline over 30 min), and recovery (70 min) in conscious rats pretreated intracerebroventricularly with vehicle or the kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI). In vehicle-pretreated rats, HSVE produced a marked increase in urine flow rate but only a low-magnitude and delayed natriuresis. RSNA was not significantly suppressed during the HSVE or recovery periods. In nor-BNI-treated rats, HSVE produced a pattern of diuresis similar to that observed in vehicle-treated rats. However, during the HSVE and recovery periods, RSNA was significantly decreased, and urinary sodium excretion increased in nor-BNI-treated animals. In other studies performed in chronic bilateral renal denervated rats, HSVE produced similar diuretic and blunted natriuretic responses in animals pretreated intracerebroventricularly with vehicle or nor-BNI. Thus removal of the renal nerves prevented nor-BNI from enhancing urinary sodium excretion during HSVE. These findings indicate that in conscious rats, endogenous central kappa-opioid systems are activated during hypotonic saline volume expansion to maximize urinary sodium retention by a renal sympathoexcitatory pathway that requires intact renal nerves.     

在大鼠牵拉心房和急性扩张血容量所致的肾效应

在28只麻醉大鼠,观察了牵拉心房和急性扩容时的肾效应。用5—7g的砝码牵拉大鼠右心房30min(n=6)时,尿量、尿钠和尿钾分别增加98％、127％和59％;牵拉左心房(n=4)所致的肾效应与牵拉右心房的基本相同。切断双侧迷走神经后,牵拉右心房的肾效应无明显改变。在切断迷走神经的大鼠,观察了双线结扎右心耳对急性扩容后肾效应的影响。急性扩容在假手术大鼠引起明显的利尿、钠尿和钾尿效应(P<0.01);而结扎右心耳的大鼠,钠尿效应约为假手术大鼠的一半,但尿量和尿钾排泄量与假手术组无明显异差。上述肾效应不受切断迷走神经的影响,因此不是通过容量感受性反射引起的。根据以上结果,我们推测,牵拉心房或急性扩容引起的尿量、尿铜和尿钾的增多,可能是心房钠尿因子释放增多所致,而结扎右心耳则导致释放入血流的心房钠尿因子减少。     

Effects of adrenalectomy and aldosterone on the action of centrally administered rat atrial natriuretic peptide-(99-126)

Intracerebroventricular (i.v.t.) administration of rat atrial natriuretic peptide-(99-126) (rANP) increases urinary volume and sodium excretion, but the mechanism is undefined. A diminished mineralocorticoid effect on the kidneys may explain the natriuretic phenomenon. This hypothesis was tested by i.v.t. rANP injection (1.25 micrograms/5 microliters) in conscious, hydrated rats pretreated beforehand with d-aldosterone (20 micrograms/kg, i.p.). Although the absolute amount of sodium excreted was reduced, aldosterone did not affect rANP-induced sodium output at 1 and 3 h. Rats which were sham-operated or bilaterally adrenalectomized (ADX) after four days were pretreated with aldosterone and given an oral water load followed by i.v.t. rANP or saline. In ADX rats natriuresis and diuresis after rANP were still evident. Our results indicate that the natriuretic effect of i.v.t. rANP is unrelated to plasma levels of mineralocorticoids. Likewise, diuresis and natriuresis can occur in the absence of the adrenal glands.     

Natriuretic and diuretic action of centrally administered rat atrial natriuretic peptide (99-126): possible involvement of aldosterone and the sympathoadrenal system

Intracerebroventricular (ICV) administration of rat atrial natriuretic peptide (99-126) (rANP) to conscious male hydrated rats resulted in a dose-related increase in urinary volume and sodium excretion over a 6-h period of urine collection. A diminished mineralocorticoid effect on the kidneys may explain the natriuretic phenomenon. This hypothesis was tested by ICV rANP injection (1.25 microgram/5 microL) in conscious hydrated rats pretreated beforehand with d-aldosterone (20 micrograms/kg, ip). Although the absolute amount of sodium excreted was reduced, aldosterone did not affect rANP-induced sodium output at 1 and 3 h. Rats that were sham-operated or bilaterally adrenalectomized after 4 days were pretreated with aldosterone and given an oral water load followed by ICV rANP or saline. The possible participation of the peripheral sympathetic nervous system in the central action of rANP was evaluated in rats pretreated with 6-hydroxydopamine. In sympathectomized and adrenalectomized rats natriuresis and diuresis were still evident after rANP. Our results indicate that the natriuretic effect of ICV rANP is independent of mineralocorticoids. Likewise, diuresis and natriuresis can occur in the absence of the adrenal glands and are independent from the neural tone that the adrenergic system exerts on sodium reabsorption.     

Changes in urine volume and urinary electrolyte excretion after intracerebroventricular injection of arecoline and hemicholinium-3

Activation of cholinergic neurons in specific brain regions evokes a hypernatriuretic response, which appears to be atropine-sensitive and, perhaps, independent from the renal innervation. However the role of cholinergic neurons in central control of renal function is not well understood. The purpose of this study was to further investigate whether brain acetylcholine stores are able to influence kaliuresis and natriuresis in conscious rats. Therefore, the renal response to cholinergic drugs was examined in Wistar rats which underwent to a 0.15 M NaCl solution (saline) load administered by gavage. Central injection of arecoline, a muscarinic agonist, produced a dose-dependent reduction in water diuresis and a highly significant increase in sodium excretion within two hours from the oral saline load. An intracerebroventricular (ICV) injection of methylatropine completely blocked both the antidiuretic and the natriuretic response induced by arecoline. Hemicholinium-3 (HC), centrally administered at a dose (34.8 nmol) known to be capable of inducing a maximal depletion of brain acetylcholine, elicited a time-dependent antidiuretic effect accompanied by a highly significant reduction in potassium and sodium urinary excretion. Therefore, we suggest that brain cholinergic neurons are involved in the regulation of the electrolyte balance.     

Studies on the role of the pituitary in the control of atrial natriuretic factor secretion and sodium excretion

Recent work suggests that hypophysectomized (HYPOX) rats show low levels of atrial natriuretic factor (ANF) and an attenuated diuresis and natriuresis to blood volume expansion. The purpose of this was (i) to examine the effect of various hormone replacements on ANF and renal excretion in HYPOX rats and (ii) to compare the renal responses to exogenous ANF in intact and HYPOX rats. Groups of rats received subcutaneous pellet implant of either dexamethasone (DEX), thyroxine (T4), or a placebo. Approximately 1 week later, they were anesthetized and subjected to a 20% blood volume expansion. DEX rats had a higher mean arterial pressure than placebo-treated rats while both MAP and heart rate were higher in T4 rats. Only the DEX rat showed augmented renal responses to volume expansion while no group showed significant changes in plasma ANF concentration during volume expansion. In a second series, groups of HYPOX rats received renal capsular transplants of either six hemi-pituitaries or six pieces of muscle which markedly raised serum prolactin levels in the hemi-pituitary group. The hemi-pituitary rats showed a greater diuresis and natriuresis during volume expansion than the muscle group and also showed a transient increase in plasma ANF. In addition, groups of either intact or HYPOX rats were anesthetized and received intravenous bolus injections of ANF. Both intact and HYPOX rats showed a very similar diuresis and natriuresis to exogenous ANF. However, potassium excretion was markedly reduced in HYPOX rats. The results show that DEX augments the renal responses to volume expansion by some mechanism which does not involve changes in plasma ANF. Thyroxine increases mean arterial pressure and heart rate in HYPOX rats but does not augment the renal or ANF responses to volume expansion. Chronic elevations in prolactin increase the renal response to volume expansion. Finally, the kidneys of HYPOX rats are capable of increasing sodium and water output in response to large doses of exogenous ANF.     

Effects of atrial appendectomy on circulating atrial natriuretic factor during volume expansion in the rat

This study examined the changes in the circulating level of endogenous atrial natriuretic factor during diuresis and natriuresis produced by acute volume expansion in anesthetized rats with either bilateral atrial appendectomy (n = 9) or sham operation (n = 9). Following control measurements in the sham-operated rats, 1% body weight volume expansion with isotonic saline produced an increment in urinary sodium excretion of over 4 mueq/min (P less than 0.05) while urine volume increased by more than 20 microliter/min (P less than 0.05). These responses were associated with a significant increase in immunoreactive plasma atrial natriuretic factor from a baseline value of 82 +/- 10 pg/ml to a level of 120 +/- 14 pg/ml (P less than 0.05). In contrast, in the group of rats with bilateral atrial appendectomy an identical degree of volume expansion increased urinary sodium excretion and urine volume by only 0.61 mueq/min (P less than 0.05) and 3.07 microliter/min (P less than 0.05), respectively. In this group, immunoreactive plasma atrial natriuretic factor remained statistically unchanged from a control value of 70 +/- 12 pg/ml to a level of 82 +/- 16 pg/ml (P greater than 0.05). Comparison of the two groups indicates that the natriuresis, diuresis, and plasma atrial natriuretic factor levels during volume expansion were significantly reduced in the rats with bilateral atrial appendectomy. No differences in mean arterial pressure and heart rate were observed between the two groups. These data demonstrate that removal of both atrial appendages in the rat attenuated the release of atrial natriuretic factor during volume expansion; and this effect, in turn, was associated with a reduction in the natriuretic and diuretic responses.