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PubMed1973

Effect of volume expansion on sodium excretion in the presence and absence of increased delivery from superficial proximal tubules.

The role of the proximal tubule in the natriuresis after volume expansion was investigated by evaluating sodium excretion both in the presence and absence of increased delivery from the proximal tubule. Proximal delivery was calculated from fractional reabsorption in superficial proximal tubules determined by micropuncture and glomerular filtration rate of the micropunctured kidney. Infusion of Ringer's solution in six dogs increased delivery from the proximal tubule 4.7+/-1 ml/min (P < 0.01) and increased fractional sodium excretion 3.6+/-1.1% (P < 0.025). Infusion of hyperoncotic albumin into the renal artery during sustained volume expansion decreased delivery from the proximal tubule 6.5+/-0.9 ml/min (P < 0.01). Although proximal delivery was restored to below control levels, fractional sodium excretion was significantly increased 2.5+/-0.5% (P < 0.01) as compared with the hydropenic control period. Fractional phosphate excretion was increased 15.5+/-3.7% (P < 0.01) after Ringer's infusion and was decreased 10.5+/-1.6% (P < 0.005) after intrarenal albumin infusion, suggesting that changes in superficial nephron reabsorption were paralleled by changes in reabsorption in deeper nephrons. Similar results were found in six additional dogs in which other factors known to affect phosphate reabsorption were controlled; however, these studies cannot completely eliminate a role for deep nephrons in the natriuresis after intrarenal albumin infusion. Since 70% of the natriuresis after volume expansion was present without increased delivery from superficial proximal tubules, it is likely that increased delivery from the proximal tubule contributes a relatively minor fraction to the natriuresis of volume expansion.

Albumins↗

PubMed1976

Evidence for hormonal participation in the natriuretic and kaliuretic responses to intraventricular hypertonic saline and norepinephrine.

To examine if hypothalamic or pituitary hormones are involved in the induction of the natriuresis which follows the injection of hypertonic saline or norepinephrine into the third ventricle, lesions were placed in the median eminence and the responses to intraventricular norepinephrine or hypertonic saline were evaluated. Sham lesions in which the electrode was lowered into the brain but stopped short of the hypothalamic region did not interfere with the natriuresis, kaliuresis, and antidiuresis induced by the third ventricular injection of either hypertonic sodium chloride or norepinephrine. Lesions in the median eminence which induced diabetes insipidus as evidenced by an increase in water consumption to approximately four times normal completely abolished the natriuresis and kaliuresis in response to intraventricular hypertonic saline or norepinephrine and diminished the antidiuresis. The observations suggest the possibility that a natriuretic hormone(s) is involved in the induction of central natriuresis.

Animals↗

PubMed1991

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).

Angiotensin Receptor Antagonists↗

PubMed2000

Renal mechanisms of angiotensin II-induced hypertension.

The kidneys play a central role in the long-term control of arterial pressure by regulating sodium balance and extracellular fluid volume. The renin-angiotensin system is important in the regulation of the arterial pressure through its chronic effects on the pressure natriuresis relationship. Under physiologic conditions, angiotensin II (Ang II) is important in causing the long-term relationship between arterial pressure and sodium excretion to be very steep, so that minimal changes in arterial pressure are necessary to maintain sodium balance in response to variations in sodium intake. An inability to suppress Ang II formation in response to increases in sodium intake can lead to salt-sensitive hypertension. Excess formation of Ang II, such as in renovascular hypertension, causes the pressure natriuresis relationship to be shifted to higher arterial pressures so that higher arterial pressures are necessary to maintain sodium balance. Ang II decreases pressure natriuresis by enhancing tubular reabsorption and/or reducing glomerular filtration. Because Ang II does not decrease glomerular filtration in most circumstances, the sodium retaining actions of Ang II are usually caused by increased tubular reabsorption. However, there are a number of pathophysiologic conditions where Ang II interacts with various local autocrine and paracrine factors (such as nitric oxide [NO], eicosanoids, adenosine, and superoxide) to influence glomerular filtration rate. Ang II enhances tubular reabsorption either indirectly, through aldosterone stimulation, via alterations in renal hemodynamics (physical factors or medullary blood flow), or by directly enhancing tubular sodium transport. Converting enzyme inhibitors or Ang II receptor antagonists improve pressure natriuresis and are very effective in the treatment of various forms of hypertension associated with normal or enhanced activity of the renin-angiotensin system.

Angiotensin II↗

PubMedDate not supplied

Interest of the association clonidine-spironolactone in cirrhotic patients with ascites and activation of sympathetic nervous system.

BACKGROUND: The aim of this study was to examine the effects of spironolactone, clonidine and the association of clonidine-spironolactone on renin-aldosterone and sympathetic systems, renal function, systemic hemodynamics and mobilization of ascites in 32 alcoholic cirrhotic patients with marked increase in sympathetic system. METHODS: Measurements were taken before and after an 8-day treatment with spironolactone (200 mg/day), after an 8-day treatment with clonidine (0.150 mg/day) and 10 days after adjunction of spironolactone (200 mg/day) to clonidine. RESULTS: Three patients abandoned the treatment or were excluded because lack of compliance. Spironolactone alone induced an increase in renin-aldosterone and sympathetic systems without any remarkable increase of natriuresis and body weight loss. Given for 8 days, clonidine alone induced a significant decrease in plasma norepinephrine associated with a significant increase in glomerular filtration rate without effect on natriuresis. In contrast, 10 days after adjunction of spironolactone to clonidine, plasma renin and aldosterone significantly decreased, natriuresis increased (from 7.4 +/- 0.7 to 41.6 +/- 3.2 mEq/24 h) and body weight decreased (from 66.03 +/- 2.3 to 63.5 +/- 2.3 kg) without adverse effects. CONCLUSION: In cirrhotic patients with ascites and marked activation of sympathetic nervous system, spironolactone (200 mg/day) is unable to mobilize ascites. In these patients, after 8 days, clonidine decreases sympathetic activity, increases glomerular filtration rate and after 18 days, decreases plasma renin and aldosterone concentrations allowing a better action of spironolactone. The association clonidine-spironolactone enhances natriuresis and body weight loss.

Adrenergic alpha-Agonists↗

PubMed1987

Comparison of the response of renal sodium excretion to almitrine and hypoxia in conscious normotensive and spontaneously hypertensive rats.

The effect of hypobaric hypoxia and almitrine on renal sodium excretion and systolic blood pressure was investigated in conscious adult normotensive control rats (NCR) and spontaneously hypertensive rats (SHR). Moderate hypoxia caused a significant natriuresis within the first two days in both NCR and SHR. The systolic blood pressure was significantly diminished in SHR only. Oral application of almitrine (1.0 mg/kg b.w.) induced natriuresis in SHR and NCR. However, there are considerable differences in the pattern of natriuresis between the animals of both strains and when compared to the effect of hypoxia. The urinary sodium excretion by almitrine was not associated with a decrease in systolic blood pressure neither in SHR nor in NCR. The results indicate that both hypoxia and almitrine induce a strong natriuresis in conscious rats apparently by different mechanisms. However, there is no real evidence at present as to whether the peripheral arterial chemoreceptors are indeed involved in these mechanisms, or not, and if so, to what degree.

Almitrine↗

PubMed1985

Effects of acute volume loading on kidney function in patients with essential hypertension, as estimated by the lithium clearance method.

This study investigated the mechanism underlying the exaggerated natriuresis seen in patients with essential hypertension. The study used the lithium clearance method, which permits accurate determination of both proximal and distal sodium reabsorption in man. One litre of isotonic sodium chloride, intravenously (i.v.), produced a significant increase in sodium excretion in patients with essential hypertension, both during and after the infusion. This increase in sodium excretion was accompanied by a significant increase in the clearance of lithium, indicating an increased output of isotonic fluid from the proximal tubules. The calculated distal reabsorption of sodium increased during the natriuresis. In the normotensive controls, sodium excretion increased only after the infusion of 1 l isotonic saline. This was accompanied by a modest increase in absolute distal sodium reabsorption. However, when the amount of saline was increased to 2 l, similar changes to those seen in hypertensives given 1 l of saline occurred in normotensive subjects. Furthermore, chronic antihypertensive treatment abolished the phenomenon of exaggerated natriuresis. It is concluded that the exaggerated natriuresis represents the normal response to sodium loading being reset to a lower level. This resetting may be a secondary consequence of the high blood pressure, since lowering the pressure abolishes the phenomenon.

Adult↗

PubMed1995

Acute environmental stress overrides cardiac volume receptor reflex in borderline hypertensive rats.

OBJECTIVE: To examine whether acute environmental stress (air-jet stress) modulates the exaggerated natriuresis to volume expansion in conscious borderline hypertensive rats. DESIGN: Intravenous isotonic saline volume expansion was performed with and without superimposed acute air-jet stress in conscious borderline hypertensive rats which had consumed a 1% NaCl diet (normotensive) or an 8% NaCl diet (hypertensive) for 12 weeks. METHODS: Conscious rats were instrumented for measurement of arterial pressure, renal sympathetic nerve activity and collection of bladder urine. RESULTS: Arterial pressure was greater in the 8% NaCl borderline hypertensive rats than in the 1% NaCl borderline hypertensive rats. In the absence of acute air-jet stress the 8% NaCl borderline hypertensive rats exhibited exaggerated natriuresis and exaggerated inhibition of renal sympathetic nerve activity compared with the 1% NaCl borderline hypertensive rats. Acute air-jet stress increased both arterial pressure and renal sympathetic nerve activity reversibly, and attenuated natriuresis in the 8% NaCl but not in the 1% NaCl borderline hypertensive rats. CONCLUSION: Acute environmental stress (air-jet stress) attenuates exaggerated natriuresis in hypertensive but not in normotensive borderline hypertensive rats via increased renal sympathetic nerve activity.

Acute Disease↗

PubMed1994

Reducing effect of atrial natriuretic factor on Na, K-ATPase activity in rat kidney.

This study was designed to examine the effect of the rat atrial extract (RAE) and synthetic rat ANF123-150 (rANF) on the renal Na, K-ATPase activity in Wistar anesthetized rats. Na, K-ATPase activity was assayed by measuring the amount of inorganic phosphate liberated from ATP. RAE from 40.3, 80.6 mg of tissue and rANF in the following doses: 0.043, 0.087, 0.173, 0.260 nM/kg/min reduced Na, K-ATPase activity by 59, 64 and 11, 34, 37, 45% respectively in the renal medulla but not in the cortex. It was associated with the increase in diuresis and natriuresis. Five and ten minutes after the end of rANF administration, Na, K-ATPase activity was decreased by 78 and 57% respectively, diuresis and natriuresis were significantly higher than the control. After fifteen minutes enzyme activity returned to normal, diuresis and natriuresis were increased. After thirty minutes there was a 37% increase in Na, K-ATPase activity but diuresis and natriuresis were still higher than control values. We conclude that the inhibition of Na, K-ATPase in the medulla of the rat kidney is one of the mechanisms of ANF action.

Animals↗

PubMed1996

Renal natriuretic effects of atrial natriuretic peptide in dogs with alloxan-induced acute pulmonary edema.

OBJECTIVE: To test the effect of atrial natriuretic peptide (ANF) in dogs with acute pulmonary edema in the absence of urinary sodium retention. ANF is normally a potent natriuretic agent, although this effect is attenuated in generalized edema or acute renal failure. DESIGN: Animal study. SUBJECTS: Twenty-nine dogs. INTERVENTION: Induction of acute pulmonary edema with intravenously administered alloxan and administration of ANF according to five protocols. OUTCOME MEASURES: Natriuretic effect of ANF before and after the induction of pulmonary edema during the protocols. RESULTS: In six control animals, induction of pulmonary edema was associated with diuresis (mean 0.38, standard error of the mean [SEM] 0.003 mL/min before alloxan administration v. mean 0.75, SEM 0.11 mL/min after); natriuresis (mean 60, SEM 8 mumol/min before v. mean 103, SEM 12 mumol/min after); and a decline in blood pressure (mean 114, SEM 7 mm Hg before v. mean 93, SEM 9 mm Hg after) and in the glomerular filtration rate (mean 52, SEM 3.3 mL/min before v. mean 36, SEM 3.7 mL/min after). When isoncotic dextran solution was infused in dogs with pulmonary edema, blood pressure was maintained but the glomerular filtration rate still declined by 42% and there was natriuresis. When the renal arteries were clamped for 5 minutes during the infusion of alloxan, diuresis and natriuresis were prevented, but the glomerular filtration rate still declined, although blood pressure was maintained. ANF administered intravenously during pulmonary edema induced a further significant natriuresis in all experimental protocols. Catalase, administered intravenously as a bolus just before the alloxan infusion, prevented pulmonary edema and the associated renal changes. CONCLUSIONS: Although alloxan appears to be directly nephrotoxic, renal damage caused by this compound does not impair the natriuretic effect of ANF in acute pulmonary edema.

Acute Disease↗

PubMed1991

Control of blood pressure by the renin-angiotensin-aldosterone system.

Modification of the renin-angiotensin system, part of a powerful feedback system for long-term control of arterial pressure and volume homeostasis, through use of angiotensin-converting enzyme (ACE) inhibitors, offers a powerful means of reducing blood pressure in many hypertensive patients. There is considerable evidence to suggest that the chronic renal and blood pressure actions of ACE inhibitors are mediated mainly by blockade of angiotensin II formation, rather than by other effects such as increased levels of kinins or prostaglandins. The long-term actions of angiotensin II and aldosterone on blood pressure are closely intertwined with their effects on volume homeostasis and the renal pressure natriuresis mechanism. In most instances, changes in angiotensin II and aldosterone act to amplify the effectiveness of pressure natriuresis and minimize changes in blood pressure needed to maintain sodium balance. When angiotensin II or aldosterone levels are inappropriately elevated, the antinatriuretic effects of these hormones shift pressure natriuresis to higher levels, thereby necessitating increased blood pressure to maintain sodium balance. Control of renal excretory function and modulation of pressure natriuresis by angiotensin II is mediated by intrarenal and extrarenal effects, including stimulation of aldosterone secretion. Current evidence indicates that the intrarenal effects of angiotensin II are quantitatively more important than changes in aldosterone in regulating renal excretion and arterial pressure. The intrarenal actions of angiotensin II include a direct effect on tubular sodium transport as well as a potent constrictor action on efferent arterioles, which increases reabsorption by altering peritubular capillary forces. The constrictor effect of angiotensin II on efferent arterioles also helps to stabilize glomerular filtration rate and therefore excretion of metabolic waste products, an action that may be particularly important when renal perfusion is impaired (e.g., in renal artery stenosis or heart failure).

Angiotensin II↗

PubMed1996

The renal paracrine peptide system--possible urologic implications of urodilatin.

Cardiodilatin/atrial natriuretic peptide (CDD/ ANP) is a hormone system of great clinical importance. The prohormone CDD/ANP-1-126 is a peptide synthesized in the heart and cleaved during exocytosis into the circulating form CDD/ANP-99-126. Urodilatin (CDD/ ANP-95-126) is a homologue natriuretic peptide that differs from CDD/ANP-99-126 by four amino acids. Whereas CDD/ANP-99-126 circulates in blood plasma and is not excreted into the urine, urodilatin is detected only in urine. Urodilatin exerts its renal effects in a paracrine fashion. After its secretion from cells in the distal tubule, it interacts with luminally located receptors in the collecting duct, resulting in increased diuresis and natriuresis. Results suggest that urodilatin plays an important role in the physiologic regulation of fluid-balance and sodium homeostasis. Pharmacology studies reveal significant differences when urodilatin and CDD/ANP-99-126 are given intravenously, showing that stronger diuresis and natriuresis are induced by urodilatin as compared with those induced by CDD/ANP-99-126. Clinical studies indicate the prophylactic and therapeutic effect of urodilatin in patients suffering from acute renal failure following heart and liver transplantation. A significant reduction in requirements for hemodialysis/hemofiltration can be achieved using urodilatin. Postobstructive diuresis and natriuresis is probably due to a defective urinary concentrating mechanism and is usually resistant to treatment with antidiuretic hormone. The distal tubule and collecting duct have often been considered to be the site of altered sodium and water excretion following relief of obstruction. Since circulating CDD/ANP-99-126 levels are markedly elevated during obstruction and decrease upon relief of the obstruction, natriuretic peptides may play an important role in this clinical feature. On the basis of recent findings attributing an important role in sodium homeostasis to urodilatin in contrast to CDD/ANP-99-126, future studies have to clarify whether urodilatin, not CDD/ANP-99-126, might be responsible for the altered renal sodium excretion observed in postobstructive diuresis. In the past decade a considerable amount of research has led to the identification and characterization of hormones of the natriuretic peptide family [13]. These peptides are involved in the regulation of salt and water homeostasis. The prototype of the natriuretic hormones is cardiodilatin/atrial natriuretic peptide (CDD/ANP), or A-type natriuretic peptide. CDD/ANP is primarily produced in the heart [6]. It is synthesized as a precursor molecule, CDD/ ANP-1-126, in specific granules in atrial myoendocrine cells [15]. The prohormone, upon appropriate stimuli for release, is cleaved into the C-terminus CDD/ANP-99-126 and excreted into the circulation via exocytosis [16]. Further members of the natriuretic peptide family are brain natriuretic peptide (BNP, or B-type natriuretic peptide) [45] and C-type natriuretic peptide (CNP) [46]. All the members of this family share many common features, including tissue distribution of gene expression, biosynthetic pathways, and pharmacologic effects in target organs [13,26]. The main biologic effects of these hormones are natriuresis, diuresis, and vasodilation [5, 6, 14, 22], but these vary among the individual peptides. Natriuretic effects such as increased glomerular filtration, inhibition of aldosterone production, and secretion result from direct inhibition of sodium absorption in the collecting duct. Urodilatin (INN: Ularitide) is a member of the natriuretic peptide family, discovered in 1988 by Schulz-Knappe et al. [43]. This hormone is presumably synthesized in the kidney and exerts potential paracrine renal effects [17]. Results of clinical phase I-II trials suggest a potent therapeutic effect of urodilatin in the treatment of acute renal failure in patients following organ transplantation [4, 27, 33].

Acute Kidney Injury↗

PubMed1986

Additive effects of atrial natriuretic polypeptide and of renal vasodilating agents in the anesthetized dog.

In order to examine the contribution of an increase in renal papillary plasma flow to the mechanism of natriuresis by atrial natriuretic polypeptide (ANP), we compared the natriuretic effects of ANP administered into the renal artery of the dog together with secretin or acetylcholine (ACh). At an equivalent renal vasodilating dose, ACh increased urinary excretion of sodium (UNaV) to 212 +/- 36% of the control associated with a decrease in urine osmolality (62 +/- 6%), whereas secretin did not change UNaV (113 +/- 12%) or urine osmolality (101 +/- 14%). This result was compatible with the view that ACh causes natriuresis mainly by increasing papillary plasma flow. Combined administration of ANP with secretin caused a marked increase in UNaV to 407 +/- 55%, in association with a decrease in urine osmolality to 55 +/- 9%, suggesting that ANP may cause natriuresis by a mechanism similar to that of ACh. Combined administration of ANP with ACh further increased UNaV to 323 +/- 67% and decreased urine osmolality to 50 +/- 6%. These observations suggest that ANP and ACh share common but not identical mechanisms of natriuretic action since ANP caused additional natriuresis during ACh infusion. These findings, however, do not necessarily exclude the possibility that ANP also inhibits renal sodium reabsorption by a direct action.

Acetylcholine↗

PubMed1997

Effect of rilmenidine on arterial pressure and urinary output in the spontaneously hypertensive rat.

Rilmenidine is an antihypertensive agent acting at the imidazoline receptor that may have both central effects in the ventral lateral medulla and direct effects on the kidney to alter Na+ excretion. The present experiments examined whether rilmenidine induces a leftward shift or change in the slope of the pressure-natriuresis curve in the spontaneously hypertensive rat (SHR). A single oral gavage dose indicated that 3 and 10 mg/kg rilmenidine significantly lowers arterial pressure at 4-12 h after administration by oral gavage. The effect of rilmenidine on pressure-natriuresis was studied using twice daily doses of 1 and 3 mg/kg for control and treated SHR drinking tap water or 1% NaCl for 3 days. Na+ excretion was measured over 24 h, and mean arterial pressure was measured 6-8 h after the morning dose of rilmenidine. The results indicate that 1 mg/kg had no effect, while the pressure-natriuresis relationship for the rats receiving the 3 mg/kg dose was shifted to the left and was not significantly different from the vertical slope of the untreated SHR. This experiment also suggested that rilmenidine may attenuate the salt preference of the rats. This was confirmed in an additional series of experiments in which the rats had access to both tap water and 1% NaCl. Thus, rilmenidine shifts the pressure-natriuresis relationship to the left and reduces salt preference in SHR.

Administration, Oral↗

PubMed1997

Comparison of the effects on urinary sodium excretion of indomethacin and of carbidopa in normal volunteers given an intravenous saline infusion.

1. Dopamine and prostaglandins are putative endogenous natriuretic hormones. The role of each in facilitating natriuresis induced by intravenous saline infusion was examined in normal volunteers in relation to administration of carbidopa, a dopadecarboxylase inhibitor, and indomethacin, an inhibitor of prostaglandin synthetase. 2. In a placebo-controlled, randomized study, 13 subjects received carbidopa (100 mg) and 12 received indomethacin (50 mg). Proximal and distal renal tubular Na+ reabsorption were determined using exogenous lithium clearance. 3. On the control day, 2 litres of 0.9% saline (308 mmol Na+) given intravenously in 3 h, resulted in volume expansion and natriuresis. Carbidopa reduced the urinary dopamine/noradrenaline ratio but showed no anti-natriuretic effect and no effect on fractional Na+ reabsorption. Indomethacin diminished natriuresis and increased distal fractional Na+ reabsorption in proportion to the antinatriuretic effect. 4. The changes in plasma concentrations of albumin, aldosterone, atrial natriuretic peptide and renin activity associated with volume expansion were not modified by either carbidopa or indomethacin. Urinary prostaglandin E2 excretion was decreased transiently by indomethacin and was unaffected by carbidopa. 5. This study suggests that prostaglandins may modulate urinary Na+ excretion during saline-induced natriuresis through inhibition of distal tubular Na+ reabsorption. No role for free dopamine as a modulator of renal Na+ handling could be assigned on the basis of the findings with carbidopa.

Adult↗

PubMed1991

Long-term effect of nifedipine and hydrochlorothiazide on blood pressure and sodium homeostasis at varying levels of salt intake in mildly hypertensive patients.

To elucidate and compare the effects of nifedipine (NIF) and hydrochlorothiazide (HCTZ) on blood pressure (BP) and sodium (Na) balance, we conducted a randomized, double-blind, crossover study with 50 mg/day HCTZ and 90 mg/day NIF (as the sustained-release gastrointestinal therapeutic system preparation) in 10 mildly hypertensive patients over approximately 8 weeks. Prior to treatment, the subjects were brought into balance at an intake of 150 mmol/day. During treatment, Na intake was lowered and raised to 50 and 300 mmol/day, respectively, in random order. Then, the subjects were brought into balance on treatment at a level of 150 mmol/day. Balance observations were made during and after the drugs were discontinued. Both HCTZ and NIF lowered BP similarly. When Na intake was lowered from 150 to 50 mmol/day, a significant decrease in diastolic BP was observed with HCTZ. Increasing Na intake to 300 mmol/day did not affect BP. At an intake of 150 mmol/day, HCTZ caused prompt natriuresis, with a negative balance of 150 mmol by 3 days. No initial natriuresis could be shown with NIF. Decreasing Na intake to 50 mmol/day caused prompt negative Na balance with both drugs; increasing it to 300 mmol/day was associated with +150 mmol Na balance with HCTZ while no significant increase was seen with NIF. Discontinuing both drugs caused prompt increase in BP and Na retention over 6 days, which was not different for the drugs. Plasma renin activity (PRA) increased with HCTZ but not with NIF. Further, changing Na intake affected PRA with HCTZ. With NIF, PRA appeared to be uncoupled from the effects of dietary Na intake. In contrast to HCTZ, no adverse metabolic effects were observed with NIF. The data suggest that NIF results in chronic mild natriuresis similar in magnitude to HCTZ. The PRA appears inactivated, although not lowered. The effects of NIF on BP may be at least in part related to the natriuresis and blunting of PRA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2005

Renal responses to atrial natriuretic peptide are preserved in bilateral ureteral obstruction and augmented by neutral endopeptidase inhibition.

PURPOSE: Atrial natriuretic peptide (ANP) contributes to post-obstructive diuresis in bilateral ureteral obstruction (BUO). In this study we examined the activity of neutral endopeptidase (NEP), an enzyme responsible for degradation of ANP, in the kidney in rats subjected to BUO for 24 hours. MATERIALS AND METHODS: Renal function was examined by the clearance method in sham operated rats and BUO rats after obstruction release. Renal responses to an intravenous bolus injection of ANP (5 microg/kg) were studied in sham operated and BUO rats with or without pretreatment with intravenous phosphoramidon (100 microg/kg per minute), a NEP inhibitor. RESULTS: In BUO rats natriuresis and diuresis occurred despite a marked decrease in the glomerular filtration rate (GFR). ANP administration increased GFR and induced marked natriuresis and diuresis in sham operated and BUO rats. Inhibition of ANP degradation by phosphoramidon induced natriuresis and diuresis, and accentuated these renal responses to ANP. CONCLUSIONS: Renal responses to ANP and renal NEP activity were preserved in 24-hour BUO. NEP inhibition to attenuate ANP degradation augmented responses to ANP in increasing GFR, natriuresis and diuresis. These findings provide the theoretical potential for facilitating the recovery of GFR after BUO release by inhibiting ANP degradation by pharmacological means.

Animals↗

PubMed1997

Role of the renal medulla in volume and arterial pressure regulation.

The original fascination with the medullary circulation of the kidney was driven by the unique structure of vasa recta capillary circulation, which Berliner and colleagues (Berliner, R. W., N. G. Levinsky, D. G. Davidson, and M. Eden. Am. J. Med. 24: 730-744, 1958) demonstrated could provide the economy of countercurrent exchange to concentrate large volumes of blood filtrate and produce small volumes of concentrated urine. We now believe we have found another equally important function of the renal medullary circulation. The data show that it is indeed the forces defined by Starling 100 years ago that are responsible for the pressure-natriuresis mechanisms through the transmission of changes of renal perfusion pressure to the vasa recta circulation. Despite receiving only 5-10% of the total renal blood flow, increases of blood flow to this region of the kidney cause a washout of the medullary urea gradient and a rise of the renal interstitial fluid pressure. These forces reduce tubular reabsorption of sodium and water, leading to a natriuresis and diuresis. Many of Starling's intrinsic chemicals, which he named "hormones," importantly modulate this pressure-natriuresis response by altering both the sensitivity and range of arterial pressure around which these responses occur. The vasculature of the renal medulla is uniquely sensitive to many of these vasoactive agents. Finally, we have found that the renal medullary circulation can play an important role in determining the level of arterial pressure required to achieve long-term fluid and electrolyte homeostasis by establishing the slope and set point of the pressure-natriuresis relationship. Measurable decreases of blood flow to the renal medulla with imperceptible changes of total renal blood flow can lead to the development of hypertension. Many questions remain, and it is now evident that this is a very complex regulatory system. It appears, however, that the medullary blood flow is a potent determinant of both sodium and water excretion and signals changes in blood volume and arterial pressure to the tubules via the physical forces that Professor Starling so clearly defined 100 years ago.

Animals↗