大鼠脑胆碱能系统对血量扩张引起利尿与尿钠排泄的作用

本工作在清醒大鼠侧脑室注射胆碱能药物,观察脑胆碱能系统对血量扩张引起利尿与尿钠排泄的作用。侧脑室注射人工脑脊液后进行血量扩张引起尿流量、排钠量和排钾量显著增加(P<0.01)。侧脑室注射胆碱能 M 受体阻断剂阿托品后,血量扩张引起尿流量、排钠量和排钾量增加的效应比注射人工脑脊液组的均显著减弱(P<0.01);而侧脑室注射胆碱能 N 受体阻断剂六烃季胺后,血量扩张引起尿流量、排钠量和排钾量增加的效应与注射人工脑脊液组的相比无显著差异(P>0.05)。侧脑室注射人工脑脊液或阿托品大鼠的肾小球滤过率(GFR)与肾血浆流量(RPF)在血量扩张后均无显著变化(P>0.05)。上述结果表明:大鼠脑胆碱能M 受体参与血量扩张引起利尿与尿钠排泄反应的调节。脑 M 受体的这种作用不是通过改变GFR 和 RPF,而可能是通过未明神经液递机制直接影响肾小管对水钠的重吸收。     

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.     

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。     

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.     

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.     

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。     

Evidence for a dopaminergic mechanism for the diuretic and natriuretic action of centrally administered atrial natriuretic factor

1. Intracerebroventricular (IVT) administration of rat atrial natriuretic factor (ANF) (99-126) to conscious male hydrated rats induces a dose-dependent increase in urine and sodium excretion. The possible involvement of brain dopaminergic system in the IVT-ANF-induced diuresis and natriuresis was evaluated. 2. Central sympathectomy (6-OHDA, 250 micrograms/5 microliters, IVT; 72 and 48 hr before IVT-ANF) inhibited both the diuretic and the natriuretic action of centrally administered ANF, suggesting that in the brain ANF requires the integrity of central noradrenergic and/or dopaminergic systems function for its actions. 3. Intracerebroventricular injection of haloperidol and intragastric administration of domperidone prevent the diuretic and natriuretic response to centrally administered ANF. 4. Our data suggest a neuromodulatory action of ANF within the brain and demonstrate an interaction of the peptide with brain dopaminergic systems.     

Role of renal nerves and vasopressin in renal responses to acute volume expansion in rats.

This study was to determine whether the presence or absence of renal nerves and vasopressin altered the diuretic and natriuretic responses to acute volume expansion. Two forms of volume expansion were used: (i) inflation of a small balloon in the veno-atrial junction and (ii) an infusion of isotonic saline at a rate of 1 ml/min for a period of 15 min, approximately 7% of body weight. Balloon inflation produced a significant diuresis from both the intact and denervated kidneys but only produced a significant natriuresis from the intact kidney. Volume expansion (infusion of saline) produced a significant diuresis and natriuresis from both intact and denervated kidneys. Blocking the V2 receptor for vasopressin with a V2-specific receptor blocker d(CH2)5[D-Ile2,Val4]AVP (40 micrograms/kg bolus dose followed by infusion of 4 micrograms/kg/min) did not alter the diuretic and natriuretic responses to volume expansion. However, the absence of renal nerves or the absence of actions of vasopressin produced a significant reduction in the capacity of the kidneys to increase the relative amount of diuresis or natriuresis, thus losing the control over output; i.e., absence of renal nerves only allowed 12-fold increase in diuresis to volume expansion compared with 25-fold in the intact state and absence of vasopressin only allowed 4.6-fold increase in diuresis to volume expansion compared with 25-fold in the intact state. Examining the "volume reflex" in terms of a control system trying to regulate fluid balance, the presence of either renal nerves or actions of vasopressin allows the volume regulating system a greater range in which to control the diuresis and natriuresis (making it possible to fine tune the output to much greater extent).     

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.