Interaction among atrial natriuretic factor (ANF), vasopressin, and renal nerves in terms of renal responses in rats.

The relationship between the renal nerves and vasopressin in terms of the natriuretic and diuretic responses to atrial natriuretic factor (ANF--0.25 microgram/kg/min for 15 min), was investigated in unilaterally denervated anesthetized rats before and after the administration of a vasopressin V2 specific antagonist (AVPX)--(40 micrograms/kg bolus followed by 0.4 microgram/kg/min infusion). Administration of the AVPX or ANF did not alter the arterial pressure. Acute renal denervation or AVPX administration independently produced significant increases in sodium and water excretion. ANF infusion by itself produced a greater increase in urine flow and sodium excretion from the denervated kidney compared to the intact kidney before the administration of AVPX. However, after the administration of AVPX renal responses to ANF from the intact kidneys were enhanced such that they were not significantly different from the denervated kidneys. These results suggest that the full physiological response to ANF may be masked by tonic renal nerve activity or antidiuretic actions of vasopressin. Furthermore, since combined renal denervation and AVPX administration does not produce any greater potentiation of the renal responses to ANF than either of these manipulations alone, it is suggested that they may act via a common mechanism, possibly altering activity in the renal nerves.     

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.     

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.     

Attenuated renal responses to atrial natriuretic factor in streptozotocin-induced diabetic rats

To determine whether the renal responses to atrial natriuretic factor (ANF) are altered in the diabetic state, the diuretic and natriuretic responses to ANF (0.25 microgram.kg-1.min-1, i.v.) were measured in streptozotocin (STZ) induced diabetic (DIA) rats. Urine flow and sodium excretion were measured before and after ANF from innervated and denervated kidneys in anesthetized (Inactin 0.1 g/kg, i.p.) control and DIA rats (Sprague-Dawley rats injected with vehicle or STZ 65 mg/kg, i.p., respectively, 2 weeks prior to the experiment). Blood glucose levels were significantly elevated in the DIA group compared with the control group. ANF produced a significantly blunted diuresis and natriuresis in DIA rats compared with control rats. In addition, reducing the hyperglycemia in DIA rats by treatment with insulin (third group) reversed the blunted urine flow and sodium excretion responses to ANF. This study demonstrates that (i) there is a blunted natriuresis and diuresis to ANF in the STZ-induced DIA rats, and (ii) restoring the glucose levels to normal by insulin treatment in the DIA rats normalized the renal responses to ANF.     

The effects of cardiac denervation on renal function.

Assessment of certain parameters of renal function were carried out before and 1 wk after total denervation of the heart by a method which leaves nerves to other organs intact. No changes in mean blood pressure, central venous pressure, cardiac output, GFR, or RPF were noted after cardiac denervation. UNaV after a low sodium diet was similar during a control period before and after denervation, but in response to expansion of the plasma volume a 3-fold greater natriuresis was seen in the denervated group. Alterations in the filtered load of sodium, the secretion of aldosterone, or most of the recently described physical and compositional factors known to influence sodium excretion cannot adequately explain this natriuresis. Expansion of an already augmented plasma volume after denervation or the possibility of a natriuretic or antinatriuretic factor with afferents interrupted in the process of cardiac denervation must be considered as etiologic factors.     

Four-hour atrial natriuretic peptide infusion in conscious rats: effects on urinary volume, sodium, and cyclic GMP

Atrial natriuretic peptide (ANP) is released from the cardiac atria in response to acute volume loads; when infused acutely ANP causes diuresis and natriuresis. Cyclic GMP (cGMP) appears to be the second messenger for ANP in the kidney. The role that ANP plays in the long-term regulation of salt and water balance is unclear, however, since resistance to ANP's natriuretic and diuretic activity develops during prolonged administration. The purpose of the present study is to examine the relationship between the rate of cGMP excretion in response to ANP and the development of resistance to ANP's diuretic and natriuretic activity. Following a 30-min baseline period of infusion of Ringer's solution conscious rats received ANP at 15 micrograms/kg/hr (n = 6) or Ringer's alone (n = 5) for 240 min. ANP-infused rats had a significant diuresis and natriuresis during the first hour of infusion; urinary cGMP excretion also increased compared to baseline. By 120 min after initiating the infusion in ANP-rats urinary volume and sodium excretion had declined to values not significantly different from those of baseline or control. In contrast, urinary cGMP excretion remained elevated for the duration of the ANP infusion, whether compared to baseline values or the control group. Resistance to the diuretic and natriuretic activity of ANP is not a result of mechanisms that involve cGMP generation.     

Vagal afferent activity and renal nerve release of dopamine

To investigate the involvement of vagal afferents in renal nerve release of catecholamines, we compared norepinephrine, dopamine, and epinephrine excretion from innervated and chronically denervated kidneys in the same rat. The difference between innervated and denervated kidney excretion rates was taken as a measure of neurotransmitter release from renal nerves. During saline expansion, norepinephrine excretion from the innervated kidney was not statistically greater than from denervated kidneys. Vagotomy increased norepinephrine release from renal nerves. Thus vagal afferents participated in the suppression of renal sympathetic nerve activity during saline expansion. No significant vagal control of dopamine release by renal nerves was detected under these conditions. Bilateral carotid ligation stimulated renal nerve release of both norepinephrine and dopamine in saline-expanded rats. The effects of carotid ligation and vagotomy were not additive with respect to norepinephrine release by renal nerves. However, the baroreflex-stimulated renal nerve release of dopamine was abolished by vagotomy. Electrical stimulation of the left cervical vagus with a square wave electrical pulse (0.5 ms duration, 10 V, 2 Hz) increased dopamine excretion exclusively from the innervated kidney of hydropenic rats. No significant change in norepinephrine excretion was observed during vagal stimulation. Increased dopamine excretion during vagal stimulation was associated with a larger natriuretic response from the innervated kidney than from its denervated mate (p less than 0.05). We conclude that under appropriate conditions vagal afferents stimulate renal release of dopamine and produce a neurogenically mediated natriuresis.     

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。     

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.     

Role of the paraventricular nucleus in renal excretory responses to acute volume expansion: role of nitric oxide

Acute volume expansion (VE) produces a suppression of renal sympathetic nerve discharge (RSND) resulting in diuresis and natriuresis. Recently, we have demonstrated that the endogenous nitric oxide (NO) system within the paraventricular nucleus (PVN) produces a decrease in RSND. We hypothesized that endogenous NO in the PVN is involved in the suppression of RSND leading to diuretic and natriuretic responses to acute VE. To test this hypothesis, we first measured the VE-induced increase in renal sodium excretion and urine flow with and without blockade of NO, with microinjection of NG-monomethyl-L-arginine (L-NMMA; 200 pmol in 200 nl), within the PVN of Inactin-anesthetized male Sprague-Dawley rats. Acute VE produced significant increases in urine flow and sodium excretion, which were diminished in rats treated with L-NMMA within the PVN. This effect of NO blockade within the PVN on VE-induced diuresis and natriuresis was abolished by renal denervation. Consistent with these data, acute VE induced a decrease in RSND (52% of the baseline level), which was significantly blunted by prior administration of L-NMMA into the PVN (28% of the baseline level) induced by a comparable level of acute VE. Using the push-pull perfusion technique, we found that acute VE induced a significant increase in NOx concentration in the perfusate from the PVN region. Taken together, these results suggest that acute VE induces an increase in NO production within the PVN that leads to renal sympathoinhibition, resulting in diuresis and natriuresis. We conclude that NO within the PVN plays an important role in regulation of sodium and water excretions in the volume reflex via modulating renal sympathetic outflow.     

Role of plasma renin activity and the renal nerves in the natriuresis of L-NMMA infusion in rats

The objective of this study was to determine the effect of N(G)-monomethyl-L-arginine (L-NMMA) infusion on plasma renin activity (PRA) in the presence or absence of the renal nerves in normotensive Wistar-Kyoto (WKY) rats and Okamoto spontaneously hypertensive rats (SHR). All rats were unilaterally nephrectomized two weeks before the acute experiment. On the day of the experiment, acute renal denervation (Dnx) of the remaining kidney was performed in one group of WKY rats (Dnx-WKY; n= 10) and one group of SHRs (Dnx-SHR: n=7). The renal nerves were left intact in a group of WKY rats (Inn-WKY; n=8) and SHRs (Inn-SHR; n=9). After a control clearance period, L-NMMA was administered i.v. (15 mg/kg bolus followed by 500 microg/kg/min infusion) and another clearance period of 20 min was taken. In all experimental groups L-NMMA infusion resulted in a significant natriuresis. L-NMMA infusion increased fractional excretion of sodium (FE(Na)) to a greater extent in the Inn-SHR than in the Inn-WKY (delta FE(Na) = 5.23+/-0.87% vs delta FE(Na) = 2.87+/-0.73% respectively; P=0.05), PRA did not change in the SHR with the infusion of L-NMMA. However, in the Inn-WKY group, the natriuresis of L-NMMA infusion was associated with a tendency for lower PRA levels as compared to a group of time control Inn-WKY rats. In Dnx-WKY, the natriuresis of L-NMMA infusion (delta FE(Na) = 4.60+/-0.52%) was associated with a significantly lower level of PRA (4.26+/-1.18 ng AI/ml/hr) as compared to a group of time control Dnx-WKY rats (9.83+/-1.32 ng AI/ml/hr; P<0.05). In the Dnx-SHR, the natriuretic response to L-NMMA infusion was significantly attenuated by renal denervation (delta FE(Na) = 2.36+/-0.34%) and PRA was unchanged. In conclusion, the natriuretic effect of systemic inhibition of nitric oxide (NO) synthesis was associated with decreased PRA in the Dnx-WKY suggesting that a potential interaction exists between NO and the renal nerves in the modulation of PRA in the normotensive WKY rat. Whereas, the natriuretic effect of L-NMMA infusion in the SHR in the presence and absence of the renal nerves, were independent of changes in PRA.     

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     

Cyclical edema in a patient with hypothalamic disorders and chronic glomerulonephritis: arginine vasopressin-dependent atrial natriuretic hormone release.

A 28-year-old woman had hypothalamic disorders (amenorrhea, obesity, psychiatric abnormalities, polydipsia and fever) and chronic glomerulonephritis. She also suffered from general edema associated with cyclical oliguria and polyuria. Her body weight and plasma osmolality increased during the oliguria phase lasting 2 to 8 days and decreased after paroxysmal polyuria accompanied by the natriuresis. These episodes occurred repeatedly, regardless of the treatment with or without diuretics. The release of arginine vasopressin in response to increased plasma osmolality was exaggerated, but changes in plasma volume did not affect arginine vasopressin release. Plasma atrial natriuretic hormone increased in response to a rise in plasma arginine vasopressin and plasma volume during the oliguria phase, thereby resulting in the diuresis and natriuresis. The renin-angiotensin-aldosterone system was secondarily activated by body fluid depletion and diuretics, and this might play an additive role in general swelling. Plasma gonadal hormones did not change to explain the edema. The mechanism of this cyclical edema remains unknown, but it is likely that hypothalamic dysfunction related to psychiatric abnormalities may exaggerate arginine vasopressin release, and enhanced renal sympathetic activity may cause retention of Na and water, and the increase in atrial natriuretic hormone release responding to the plasma volume expansion may bring about the diuresis and natriuresis.     

Regulation of arterial pressure: role of pressure natriuresis and diuresis

The importance of the renal pressure natriuresis and diuresis mechanisms in long-term control of body fluid volumes and arterial pressure has been controversial and difficult to quantitate experimentally. Recent studies, however, have demonstrated that in several forms of chronic hypertension caused by aldosterone, angiotensin II (AngII), vasopressin, or norepinephrine and adrenocorticotropin, increased renal arterial pressure is essential for maintaining normal excretion of sodium and water in the face of reduced renal excretory capability. When renal arterial pressure was servo-controlled in these models of hypertension, sodium and water retention continued unabated, causing ascites, pulmonary edema, or even complete circulatory collapse within a few days. Apparently, other mechanisms for volume homeostasis, such as the various natriuretic and diuretic factors that have been postulated, are not sufficiently powerful to maintain fluid balance in the absence of increased renal arterial pressure when renal excretory function is reduced in these forms of hypertension. The intrarenal mechanisms responsible for pressure natriuresis and diuresis are not entirely clear, but they seem to involve small increases in glomerular filtration rate and filtered load as well as reductions in fractional reabsorption in proximal and distal tubules. During chronic disturbances of arterial pressure additional factors, especially changes in AngII and aldosterone formation, act to amplify the effectiveness of the basic renal pressure natriuresis and diuresis mechanisms in regulating arterial pressure and body fluid volumes.     

Potentiation of the natriuretic effect of clonidine following indomethacin in the rat.

Previous studies have demonstrated a diuretic effect of clonidine at low intrarenal infusion rates with a natriuretic effect being observed at high infusion rates (greater than or equal to 3 micrograms.kg-1.min-1). The natriuresis at high infusion rates may have been secondary to increased renal prostaglandin production. We therefore evaluated the effects of indomethacin (a cyclooxygenase inhibitor) on the response to clonidine in the anesthetized rat. Intrarenal infusions of saline (vehicle) or clonidine (0.1, 0.3, 1, and 3 micrograms.kg-1.min-1) were examined both in the presence and absence of pretreatment with indomethacin (5 mg/kg, i.p.). Clonidine produced a dose-related increase in urine volume and free water clearance at 0.3, 1, and 3 micrograms.kg-1.min-1 as compared with the vehicle group. Sodium excretion and osmolar excretion were increased only at the highest infusion rate investigated. Following indomethacin pretreatment, clonidine produced a greater increase in urine volume at each infusion rate investigated. The indomethacin pretreatment also resulted in a potentiation of the natriuretic effect of clonidine at all infusion rates. Interestingly, this was associated with an increase in osmolar clearance but not free water clearance. These effects of indomethacin were reversed by infusion of prostaglandin E2. An infusion of prostaglandin E2 attenuated the indomethacin-induced increase in both urine flow rate and sodium excretion, indicating that the effects of indomethacin were mediated by prostaglandin inhibition. These results suggest that endogenous prostaglandin production attenuates the renal effects of clonidine, and as well, that in the presence of alpha 2-adrenoceptor stimulation, prostaglandin E2 mediates an antidiuretic and antinatriuretic effect.     

Attenuated diuretic and natriuretic effects of atrial natriuretic peptide in rats with heart failure

Plasma levels of atrial natriuretic peptide (ANP) and renal responses to ANP were examined in rats with chronic cardiac failure produced by coronary artery ligation and in sham-operated controls. Plasma ANP levels were elevated in the rats with severe cardiac failure as compared with the controls (P less than 0.001). ANP injections at the doses of 1, 5, 25 and 50 micrograms/kg increased water and sodium excretion significantly at all but the lowest dose in the controls; only the two largest doses caused clear diuresis and natriuresis in the heart failure group. The diuretic and natriuretic effects of ANP were significantly weaker at the doses of 5 and 25 micrograms/kg in the rats with heart failure as compared with the controls. We conclude, that natriuretic and diuretic effects of ANP are attenuated in this chronic heart failure mode.     

The renal excretory activity of atrial natriuretic factor is independent of renal prostaglandins in humans.

Since renal prostaglandins may contribute to natriuresis induced by endogenous atrial natriuretic factor (ANF), acute volume expansion (AVL), a known stimulus of ANF and prostaglandins, was induced in 8 healthy women in order to test whether the consequent sodium and water diuresis is altered by prostaglandin inhibition. AVL (i.v. infusion of a 2 liter 5% glucose solution in 1 h) was infused after placebo and after inhibition of prostaglandins with diclofenac (200 mg/day orally for 4 days), in a double blind randomized cross-over fashion. Urinary eicosanoids (PGE2, PGF2 alpha, 6-ketoPGF1 alpha, TXB2--RIA), plasma ANF (RIA) and urinary electrolytes were determined before, during and after AVL under both placebo and diclofenac regimes. During placebo, AVL induced sustained increases in plasma ANF (174% at peak, p less than 0.001 ANOVA), excretion of the four eicosanoids (149%-1172%, p less than 0.005-0.001), urinary volume (UV, 815%, p less than 0.001), natriuresis (UNa, 98%, p less than 0.005) and in kaliuresis (UK, 90%, p less than 0.001). Cyclooxygenase inhibition resulted in a reduction of over 70% in both baseline values and AVL-induced increase of eicosanoids. It did not alter either baseline levels or AVL-stimulated ANF, UV, UNa and UK in relation to placebo. The present results suggest that the diuretic and natriuretic activity of ANF is not mediated by renal PGs in humans.     

Atrial natriuretic factor (ANF) increases urinary protein excretion in patients with essential hypertension: a possible role of ANF for renal handling of protein

Low dose iv infusion (0.01 and 0.03 micrograms/kg per min, for 30 min each) of alpha-human atrial natriuretic factor (alpha-hANF) produced a significant increase (+300%) in urinary protein excretion in patients with essential hypertension but not in normotensive controls, when their renal function was normal. The major component of excreted proteins induced by alpha-hANF infusion was presumed to be albumin on the basis of molecular weight (69,000) analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Urine output and sodium and potassium excretion rates were increased dose-dependently by alpha-hANF infusion in the hypertensive patients in a similar fashion to those in the controls. Glomerular filtration rate (GFR) remained unchanged in the controls but was slightly increased in the patients (+33%) during the infusion. These results suggest that besides its previously recognized physiological functions such as natriuresis and diuresis, ANF plays an important role in the regulation of renal handling of proteins in patients with essential hypertension.