Acute Sodium Loading Research Articles

Renal hyporesponsiveness to brain natriuretic peptide: Both generation and renal activity of cGMP are decreased in patients with pulmonary hypertension

We examined the mechanisms of renal resistance to atrial and brain natriuretic peptides (ANP and BNP) in pulmonary hypertension (PH). Compared to eight controls, nine PH patients showed a reduced ability to excrete an acute sodium load despite increased circulating ANP, BNP and cyclic guanosine monophosphate (cGMP), their second messenger. Patients’ reduced urinary cGMP/BNP and natriuresis/urinary cGMP ratios demonstrated impaired generation of and reduced renal response to cGMP, respectively. Therefore, PH patients hyporesponsiveness to cardiac natriuretic peptides is likely located both upstream and downstream cGMP generation. Natriuretic peptide signalling pathway disruptions might be accessible to therapy.

The role of PPAR‐alpha: in the regulation of blood pressure and renal function in salt‐loaded animals

PPAR-alpha, a member of the super family of nuclear receptors is highly expressed in several tissues including the vasculature and the kidney. Its role in the regulation of renal function and blood pressure (BP) is suggested but there are no definitive studies. However, in our previous study, PPAR-alpha activators increased nitric oxide (NO) production. In this study, we evaluated the contribution of PPAR-alpha to renal function and BP in PPAR-alpha null (KO) mice and wild type (WT) littermates placed on normal (NS; 0.3% NaCI) or high salt (HS; 8% NaCI) diet for 3 weeks. Systolic BP (plethysmography) was greater (124 mmHg) in WT mice placed on HS diet as did nitrite excretion (UNOxV), urinary volume (UV) and sodium excretion (UNaV). However, SBP, UNOxV, UNaV was similar in KO mice placed on NS or HS diet. In KO and WT mice placed on acute sodium load (2.5 ml/100g i.p), 5-hour UV and UNaV was similar (WT, 0.64 ml; KO, 0.50 ml). In amiloride-treated mice, UV and UNaV was greater in KO mice (0.26 ml vs 1.26 ml). These data suggest that PPAR-alpha contributes to the regulation of renal function affecting UNaV via amiloride-insensitive transport mechanisms.

Central hemodynamic responses to an acute sodium load in black and white subjects.

Chronically high dietary sodium intake has been associated with elevated blood pressure (BP). Studies have shown that black adults demonstrate a higher degree of sodium sensitivity than white adults. PURPOSE To examine the acute effects of sodium on BP, cardiac output (Qc), and peripheral vascular resistance (PVR) in black and white subjects. We hypothesized that a hypertonic saline infusion (3% NaCl; HSI) would increase BP more in black subjects. METHODS 19 black (age: 22.9 ± 1.4 yrs) and 16 white (age: 25.9 ± 1.5 yrs) healthy subjects underwent a 60-minute HSI. BP (Finometer), Qc (CO2 rebreathing), serum sodium, and osmolality were assessed throughout the HSI. PVR was calculated. Results are reported as mean ± standard error and a two way repeated measures ANOVA was used to compare the effects of time and race. RESULTS During the HSI there was an increase in serum sodium (135.3 ± 0.4 to 141.1 ± 0.4 mmol/L) and osmolality (287.4 ± 0.7 to 296.6 ± 0.7) that was not different between the races. While the increase in mean BP was not different between the races (black: 10.1 mmHg vs. white: 9.5 mmHg, p = 0.795), the time course for the change in Qc (and hence, PVR) was different (ANOVA race, p < 0.05). CONCLUSION Preliminary analysis suggests that the HSI increased BP in all subjects, but the mechanisms underlying the change in BP were different black and white subjects. Supported by NIH grant RI5 HL074851-01.

Renal nerves and nNOS: Roles in natriuresis of acute sodium loading

We investigated the role of renal nerves and nNOS in the response to acute, mild sodium loading in conscious Sprague-Dawley female rat. Animals were subjected either to bilateral renal denervation or sham-operated. The rats were permanently provided with arterial, venous and bladder catheters. Denervated and sham rats were exposed to a hypertonic saline load (50 μmol/kg/min, 120 min.) with and without treatment with a nNOS inhibitor, S-methylthiocitrulline (SMTC, 20 μg/kg/min). Control experiments included isotonic infusion at the same flow of 25 μl/kg/min. Renal denervation decreased MABP (101±2 vs. 112±2 mmHg, mean±SE). SMTC treatment increased MABP in both denervated and sham rats to 110±2 and 118±2 mmHg, respectively. Denervated rats had lower plasma renin concentration (PRC) than sham (14±1 vs. 20±1 mIU/L). The control value of inulin clearance for denervated rats was lower than for sham (2.2±0.2 vs. 2.6±0.1 ml/min). Sodium loading increased MABP similarly in all situations (6-9 mmHg). SMTC treatment lowered PRC control values in sham rats to values similar to denervated. A progressive increase in PAH clearance during sodium loading was absent in both groups with SMTC treatment. In contrast to denervated rats, the treatment of sham rats with SMTC augmented the natriuretic response to the sodium load to a peak value of 16±2 μmol/min compared to 12±1 μmol/min. It is concluded (i) that the renal nerves are unimportant to the present natriuretic response but mediate a tonic pressor effect on MABP, and (ii) that the reputed nNOS inhibitor blunts the renal hemodynamic and augments the natriuretic response to an acute sodium load. Supported by The Danish Research Council

Blood pressure and hemodynamic responses to an acute sodium load in humans

The purpose of this study was to investigate the acute blood pressure (BP) and hemodynamic effects of sodium chloride (3% intravenous solution). Although many studies link a change in dietary sodium to a change in BP, few consider the effects of sodium concentration in the blood on BP. We hypothesized that an intravenous sodium load would increase BP, and we quantified alterations in cardiac output (Qc) and peripheral vascular resistance (PVR). Thirteen subjects (age 27 +/- 2 yr) underwent a 60-min 3% saline infusion (0.15 ml.kg(-1).min(-1)). BP was assessed on a beat-to-beat basis with a Finometer, Qc was assessed via the CO(2) rebreathing technique, and PVR was derived. Serum sodium and osmolality increased, and hematocrit declined during the infusion (ANOVA, P < 0.01). Mean arterial pressure (MAP) increased continuously during the infusion from 81.8 +/- 3.4 to 91.6 +/- 3.6 mmHg (ANOVA, P < 0.01). BP responsiveness to sodium was expressed as the slope of the serum sodium-MAP relationship and averaged 1.75 +/- 0.34 mmHg.mmol(-1).l(-1). BP responsiveness to the volume change was expressed as the slope of the hematocrit-MAP relationship and averaged -2.2 +/- 0.35 mmHg/%. The early change in MAP was mediated by an increase in Qc and the late change by an increase in PVR (P < 0.05), corresponding to a 30% increase in plasma norepinephrine. In conclusion, an acute infusion of hypertonic saline was effective in increasing BP, and both sodium and volume appear to be involved in this increase; acute BP responsiveness to serum sodium can be quantified using a MAP-sodium plot.

Increased dietary sodium inhibits baroreflex-induced bradycardia during acute sodium loading

The present study investigated the effects of increased dietary sodium on the modification of cardiac baroreflex responses induced by acute sodium loading. Changes in blood pressure and heart rate during intravenous phenylephrine and nitroprusside administration were compared using a four-parameter sigmoid logistic function before and after a 30-min infusion of 0.6 or 1.0 M NaCl in conscious male Sprague-Dawley rats consuming only tap water (Tap) or isotonic saline (Iso) for 2-3 wk. In Tap animals, infusion of 1.0 M NaCl increased the baroreflex-induced heart rate minimum, reduced heart rate range, and increased the operating blood pressure. In contrast, infusion of 0.6 M NaCl in Tap rats reduced both heart rate minimum and maximum. However, infusion of 0.6 M NaCl in Iso animals produced responses similar to that shown in Tap rats infused with 1.0 M NaCl. In addition, the decreased heart rate minimum in Tap rats after infusion of 0.6 M NaCl was prevented by intravenous administration of a vasopressin V1-receptor antagonist. Furthermore, cardiac parasympathetic responses were similar in Tap and Iso rats before and after 0.6 M NaCl infusion. However, in animals receiving intravenous atropine, 0.6 M NaCl decreased heart rate minimum and maximum in Tap but did not alter the response parameters in Iso rats. These results demonstrate that the facilitation of cardiac baroreflex responses normally observed during moderate sodium loading is mediated by vasopressin and that increased dietary sodium ingestion reverses this facilitation by reducing sympathetic nervous system withdrawal.

Increased dietary sodium enhances activation of neurons in the medullary cardiovascular pathway during acute sodium loading in the rat

Increased sodium ingestion diminishes baroreflex-induced bradycardia in animals during acute sodium loading. These experiments studied effects of high sodium diet on activation of central nervous system sites associated with baroreflex activation and cardiovascular responses to hypernatremia during systemic sodium administration. Fos-like (Fos-Li) protein immunoreactivity was measured to estimate activation of neurons in the medullary baroreflex pathway (nucleus tractus solitarius (NTS), caudal ventrolateral medulla (CVLM), and rostral ventrolateral medulla (RVLM)), and in the hypothalamic paraventricular (PVN) and supraoptic nuclei (SON) in male Sprague–Dawley rats consuming standard chow and either tap water (TAP) or isotonic saline (ISO) for 2–3 weeks. Fos-Li immunoreactivity in the PVN and SON was similar in rats consuming TAP and ISO infused with 0.6 M NaCl. However, there were significantly more Fos-Li positive cells in NTS and CVLM of animals consuming ISO and infused with 0.6 M NaCl than any other experimental group, while Fos-Li immunoreactivity was similar in the RVLM in all animals. In conclusion, these data demonstrate that activation of neurons in the NTS and CVLM was significantly enhanced by moderate sodium loading in animals consuming high dietary sodium. The increased basal activation of neurons in these medullary sites could account for decreased baroreflex-induced bradycardia observed during ingestion of a high salt diet and acute, moderate sodium loading.

Responses to a saline load in gonadotropin-releasing hormone antagonist-pretreated premenopausal women receiving progesterone or estradiol-progesterone therapy.

The effects of estradiol (E(2)) and progesterone (P(4)) on fluid and sodium regulation may have important clinical implications with respect to cardiovascular and renal disease as well as reproductive syndromes such as preeclampsia and ovarian hyperstimulation syndrome. We tested the hypothesis that sodium excretion is reduced in response to a sodium load during combined P(4)-E(2) treatment, but P(4) administration alone has little effect on sodium regulation. Fifteen women (22 +/- 2 yr) used a GnRH antagonist to suppress endogenous E(2) and P(4) for 9 d; for d 4-9, eight subjects used P(4) (200 mg/d), and seven subjects used P(4) with E(2) (two E(2) patches, 0.1 mg/d each). On d 3 and 9, isotonic saline (0.9% NaCl) was infused [120 min at 0.1 ml/kg body weight (BW).min], followed by 120 min of rest. Compared with GnRH antagonist alone, P([P4]) increased from 1.6 +/- 0.8 to 9.4 +/- 2.3 ng/ml (5.1 +/- 2.5 to 29.9 +/- 7.3 nmol/liter, P < 0.05) in the P(4) treated group, with no change in P([E2]). In the P(4)-E(2) treated group P([P4]) increased from 1.6 +/- 0.5 to 6.7 +/- 0.6 ng/ml (5.1 +/- 1.6 to 21.3 +/- 1.6 nmol/liter, P < 0.05 and P([E2]) increased from 17.9 +/- 6.3 to 200 +/- 41 pg/ml (65.7 +/- 23 to 734.6 +/- 150.0 pmol/liter, P < 0.05). Before isotonic saline infusion, renal sodium and water excretion were similar under all conditions, but during isotonic saline infusion, cumulative sodium excretion was lower in the P(4)-E(2) treated women (34.1 +/- 5.1 mEq) compared with GnRH antagonist (50.2 +/- 11.4 mEq). Sodium excretion was unaffected by P(4) treatment (48.0 +/- 8.2 and 41.2 +/- 5.1 mEq, for GnRH antagonist and P(4)). Compared with GnRH antagonist alone, P(4)-E(2) treatment increased distal sodium reabsorption and transiently decreased proximal sodium reabsorption, whereas P(4) treatment did not alter either distal or proximal sodium reabsorption. Before isotonic saline infusion, the plasma aldosterone (Ald) concentration was greater during P(4) treatment (153 +/- 25 pg/ml; 3883 +/- 1102 pmol/liter) and P(4)-E(2) treatment (242 +/- 47 pg/ml; 6373 +/- 1390 pmol/liter) than during their respective GnRH antagonist alone treatments [96 +/- 13 and 148 +/- 47 pg/ml (2598 +/- 475 and 3284 +/- 973 pmol/liter) for P(4) and combined P(4)-E(2), respectively]. Compared with GnRH antagonist alone treatments, preisotonic saline infusion plasma renin activity was greater only with P(4)-E(2) treatment, whereas the plasma atrial natriuretic peptide concentration was lower only with P(4) treatment. Isotonic saline infusion suppressed plasma Ald under all conditions, but decreased plasma renin activity only with P(4)-E(2) treatment (average decrease, 1.3 +/- 0.5 ng/ml angiotensin I.h; P < 0.05). In summary, we found that P(4)-E(2) treatment decreased sodium excretion via either renin-angiotensin-Ald system stimulation or direct effects on kidney tubules. P(4) treatment at these plasma concentrations had no independent effect on the renal response to acute sodium loading. These data suggest that E(2) is the more powerful reproductive hormone involved in sodium retention relative to P(4), and that estrogen-induced up-regulation of P(4) receptors is required for the effects of P(4) on sodium regulation.

More on the sodium saga.

The relationship between sodium (salt) intake and blood pressure has been convincingly established by epidemiological, observational, interventional, physiological, and some genetic evidence for some time. Yet the interaction remains the subject of passionate and heated debate. Even among those who are convinced of the salt–blood pressure interaction, some advocate a population-wide attempt to reduce dietary salt intake, arguing on the basis of epidemiological and interventional evidence, and others who suggest that such interventions should be targeted toward those most likely to benefit: the “salt-sensitive” subpopulation. Studies have characterized such subgroups on the basis of higher blood pressure, increased age or African-American ethnicity.1 The issue is rendered even more compelling by the findings that salt sensitivity can be identified among “normotensive” subjects (ie, those with blood pressure <140/90) as well as those with hypertension1 and the designation of those with blood pressure levels between 120 and 139 mm Hg systolic and 80 and 89 diastolic as prehypertensive2 and at increased risk for development of fixed hypertension and for cardiovascular events compared with those with lower blood pressure.3 Observational data have provided a starting point for the quantitative considerations of dietary salt intake. The most recent (1999–2000) NHANES survey provides an estimated dietary sodium intake based on food records, excluding discretionary sodium, of 135 to 204 mmol per day for men and 100 to 135 mmol per day for women in the United States.4 Questionnaires are acknowledged to underestimate actual intake, and urinary sodium excretion has been shown to provide a more accurate index of total sodium intake because it represents ≈93% of intake at steady-state conditions.5 A recent British survey reported that urinary sodium excretion averaged 187 mmol per day for men and 139 mmol per day for women.5 This was very similar to …

Volume natriuresis vs. pressure natriuresis.

Body fluid regulation depends on regulation of renal excretion. This includes a fast vasopressin-mediated water-retaining mechanism, and slower, complex sodium-retaining systems dominated by the renin-angiotensin aldosterone cascade. The sensory mechanisms of sodium control are not identified; effectors may include renal arterial pressure, renal reflexes, extrarenal hormones and other regulatory factors. Since the pioneering work of Guyton more than three decades ago, pressure natriuresis has been in focus. Dissociations between sodium excretion and blood pressure are explained as conditions where regulatory performance exceeds the precision of the measurements. It is inherent to the concept, however, that sudden transition from low to high sodium intake elicits an arterial pressure increase, which is reversed by the pressure natriuresis mechanism. However, such transitions elicit parallel changes in extracellular fluid volume thereby activating volume receptors. Recently we studied the orchestration of sodium homeostasis by chronic and acute sodium loading in normal humans and trained dogs. Small increases in arterial blood pressure are easily generated by acute sodium loading, and dogs appear more sensitive than humans. However, with suitable loading procedures it is possible - also acutely - to augment renal sodium excretion by at least one order of magnitude without any change in arterial pressure whatsoever. Although pressure natriuresis is a powerful mechanism capable of overriding any other controller, it seems possible that it is not operative under normal conditions. Consequently, it is suggested that physiological control of sodium excretion is neurohumoral based on extracellular volume with neural control of renin system activity as an essential component.

Dietary sodium and blood pressure.

The importance of dietary sodium chloride in the regulation of blood pressure has received much attention over the past few years. This area of research and knowledge has been controversial for several reasons. The major reason for controversy is that the science of the relationship is difficult to ascertain. Population science is limited by the narrow range of dietary sodium intake by most populations and individuals and the multiple confounders in those populations at the extremes of intake. Results from clinical trials have been difficult to interpret because of the difficulty in maintaining a given level of sodium intake over a period of time sufficient for study. Furthermore, basic science studies have been challenged by identifying appropriate models that mimic salt-sensitive hypertension in humans. Moreover, a lack of a well-funded proponent in industry complicates the research challenges. Guyton’s concept that the role of the kidney in handling sodium is key to the long-term regulation of blood pressure is now generally accepted.1 However, the exact role that dietary sodium plays in this relationship remains controversial. The relationship between renal handling of sodium and blood pressure is apparently influenced by a complex combination of factors including nutritional, other environmental, genetic, neurohormonal, and metabolic factors. The skepticism of many regarding the role of dietary sodium in blood pressure regulation and control has been tempered by the results of the DASH sodium study.2 Most acknowledge that this study reliably confirmed the benefit of dietary sodium restriction in blood pressure management. The study showed a dose-dependent impact of dietary sodium restriction on blood pressure in older hypertensive and nonhypertensive subjects. For many interested in this area of research, the questions have shifted as a result of the DASH sodium study. Rather than questioning whether dietary sodium is important, many investigators have turned their …

The acute sodium loading test revisited: Does determination of plasma renin increase diagnostic accuracy for primary hyperaldosteronism?

The acute sodium loading test revisited: Does determination of plasma renin increase diagnostic accuracy for primary hyperaldosteronism?

Body sodium and volume homeostasis.

maintenance of a “milieu interieur,” which allows our cells to function away from the ancient sea, is one of the most important functions of the body. Maintenance of constant extracellular osmolarity and sodium concentration depends on a precise balance between intake and excretion of sodium and

Sodium loading changes urinary protein excretion: a proteomic analysis.

Plasma sodium concentration is maintained even when sodium intake is altered. Sodium homeostasis may involve changes in renal tubular protein expression that are reflected in the urine. We used proteomic analysis to investigate changes in urinary protein excretion in response to acute sodium loading. Rats were given deionized water followed by hypertonic (2.7%) saline for 28 h each. Urinary protein expression was determined during the final 4 h of each treatment. Acute sodium loading increased urinary sodium excretion (4.53 +/- 1.74 vs. 1.70 +/- 0.27 mmol/day, P = 0.029). Urinary proteins were separated by two-dimensional PAGE and visualized by Sypro ruby staining. Differentially expressed proteins were identified by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry followed by peptide mass fingerprinting. The abundance of a total of 45 protein components was changed after acute sodium loading. Neutral endopeptidase, solute carrier family 3, meprin 1alpha, diphor-1, chaperone heat shock protein 72, vacuolar H(+)-ATPase, ezrin, ezrin/radixin/moesin-binding protein, glutamine synthetase, guanine nucleotide-binding protein, Rho GDI-1, and chloride intracellular channel protein 1 were decreased, whereas albumin and alpha-2u globulin were increased. Some of these proteins have previously been shown to be associated with tubular transport. These data indicate that alterations in the excretion of several urinary proteins occur during acute sodium loading.

Reduced natriuretic response to acute sodium loading in COMT gene deleted mice.

The intrarenal natriuretic hormone dopamine (DA) is metabolised by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). Inhibition of COMT, as opposed to MAO, results in a potent natriuretic response in the rat. The present study in anaesthetized homozygous and heterozygous COMT gene deleted mice attempted to further elucidate the importance of COMT in renal DA and sodium handling. After acute intravenous isotonic sodium loading, renal function was followed. COMT activity in heterozygous mice was about half of that in wild type mice and was zero in the homozygous mice. MAO activity did not differ between the genotypes. Urinary sodium excretion increased 10-fold after sodium loading in wild type mice. In heterozygous and homozygous mice, the natriuretic effects of sodium loading were only 29 % and 39 %, respectively, of that in wild type mice. Arterial pressure and glomerular filtration rate did not differ between genotypes. Baseline norepinephrine and DA excretions in urine were elevated in the homozygous, but not in heterozygous, COMT gene deleted mice. Urinary DA excretion increased after isotonic sodium loading in the wild type mice but not in the COMT gene deleted mice. Mice with reduced or absent COMT activity have altered metabolism of catecholamines and are unable to increase renal DA activity and produce normal natriuresis in response to acute sodium loading. The results support the hypothesis that COMT has an important role in the DA-mediated regulation of renal sodium excretion.

Role of plasma ANG II in the excretion of acute sodium load in a bird with salt glands (Anas platyrhynchos).

This study was designed to further examine the role of plasma ANG II in the excretion of sodium in the Pekin duck, a bird with salt glands. Renal and extrarenal (salt gland) excretion of an intravenously administered isotonic saline load was monitored over a 4-h period in a group of eight birds under two conditions: the control condition, in which isotonic saline infusion decreased endogenous plasma ANG II from 102.6 to 16.5 pg/ml, and the experimental condition, in which ANG II suppression was prevented by intravenous infusion of a 3.5 ng. kg(-1). min(-1) dose of synthetic ANG II. ANG II infusion significantly decreased the total sodium excretion (by 15%), primarily via an inhibition of salt gland output. The results suggest that ANG II suppression facilitates the excretion of an administered sodium load in birds with salt glands.

Reduced natriuresis after oral sodium load in cholestatic rats: role of compartment volumes and ANP.

The purpose of this study was to assess the participation of the atrial natriuretic peptide (ANP)-cGMP system in electrolyte and volume handling of cholestatic rats submitted to an acute oral sodium load. Cholestasis was induced by ligation and section of the common bile duct (n = 51). Control rats were sham operated (n = 56). Three weeks after surgery, 24-hr urinary volume, sodium, potassium, cGMP and creatinine excretion were measured. Three days later, animals received 10 mmol/kg NaCl (1 M) by gavage, and urinary excretion was measured for 6 hr. In parallel groups of rats, plasma volume, electrolytes and ANP concentration, extracellular fluid volume (ECFV), and renal medullary ANP-induced cGMP production were determined in basal conditions or 1 hr after oral sodium overload. As compared with controls, cholestatic rats had a larger ECFV and higher plasma ANP (67.2 +/- 5.2 vs 39.7 +/- 3.5 pg/ml), but lower hematocrit and blood volume, and were hyponatremic. Cholestatic rats showed higher basal excretion of sodium, potassium, and volume than controls, but equal urinary cGMP. After the NaCl overload, cholestatic rats showed a reduced sodium excretion but equal urinary cGMP. One hr after sodium overload, both groups showed hypernatremia, but whereas in control rats ECFV and ANP increased (50.7 +/- 4.1 pg/ml), in cholestatic rats ECFV was unchanged, and plasma volume and ANP were reduced (37.5 +/- 5.8 pg/ml). ANP-induced cGMP production in renal medulla was similar in cholestatic and control nonloaded rats (14.2 +/- 5.2 vs 13.4 +/- 2.6 fmol/min/mg). One hr after the load, medullary cGMP production rose significantly in both groups, without difference between them (20.6 +/- 3.1 vs 22.7 +/- 1. 7 fmol/min/mg). We conclude that the blunted excretion of an acute oral sodium load in cholestatic rats is associated with lower plasma ANP due to differences in body fluid distribution and cannot be explained by renal refractoriness to ANP.

Supranormal natriuretic response to volume expansion in vagotomized and renal-denervated rats.

1. To investigate the participation of both vagal cardiopulmonary baroreceptor activity and efferent renal sympathetic nerve activity (ERSNA) in the natriuretic response to saline volume expansion (SVE), three series of experiments were undertaken in anaesthetized rats. 2. In the first two series of experiments, the natriuretic (series A) and ERSNA (series B) responses to SVE were evaluated in both sham operated and cervical bilateral vagotomized rats. The acute experiment consisted of two baseline (BL) periods, treatment (sham control (CTR) or real cervical bilateral vagotomy), a volume expansion phase (Ringer's solution, 10% bodyweight) and a postexpansion phase. The results of these two series indicate that vagotomy significantly enhances basal ERSNA (37 +/- 8%; P < 0.05 vs BL) and significantly attenuates the renal sympathoinhibitory response (by approximately 50%; P < 0.05 vs CTR) but not the natriuretic response to SVE, suggesting the potential expression of a vagotomy induced compensatory natriuretic mechanism. 3. To assess this, the natriuretic response to SVE was evaluated in chronic sham operated or renal denervated groups of rats in which vagotomy was or was not performed (series C). There were no differences among groups in either systemic haemodynamics or plasma protein concentration. Vagotomy plus chronic renal denervation induced a supranormal natriuretic and diuretic response (approximately 30%; P < 0.01) to SVE when compared with similar natriuretic and diuretic responses of the remaining groups. 4. These data support the idea that, in intact rats on a normal sodium diet, neither cardiopulmonary baroreceptors nor renal nerves are necessary for the elimination of an acute intravenous isotonic sodium load and indicate that during SVE the activation of vagal cardiopulmonary baroreceptors exerts an inhibitory effect on both ERSNA and the expression of a natriuretic mechanism. Such a natriuretic mechanism is expressed only when SVE is induced in vagotomized rats (compensating for the vagotomy mediated antinatriuretic effects of an enhanced ERSNA), but is unmasked only when, in addition, renal nerves are chronically transected. All of this offers an efficient element of safety in eliminating an acute isotonic sodium load when cardiopulmonary baroreceptors are severed.

Renal dopaminergic system participates in the natriuretic responses to acute sodium load in black salt-resistant but not in salt-sensitive subjects.

Renal dopaminergic system participates in the natriuretic responses to acute sodium load in black salt-resistant but not in salt-sensitive subjects.

Mechanisms underlying the decrease in circulating angiotensin II concentration after sodium loading.

1. Acute sodium loading causes a rapid decrease in the circulating concentration of angiotensin II (AngII), which is apparent from 5 min after sodium administration. This could result from an increase in AngII catabolism and/or a decrease in AngII synthesis/secretion. However, the major determinant of AngII synthesis is thought to be a change in plasma renin activity, which occurs over a longer time frame (15 min). 2. To investigate the mechanisms underlying the rapid decrease in plasma AngII engendered by sodium administration, we performed metabolic clearance studies in male New Zealand white rabbits before and after a hypertonic sodium load of 1.5 mmol/kg as 0.513 mol/L saline i.v. bolus. 3. The metabolic clearance rate of AngII increased significantly from 42.2 +/- 9.0 mL/min per kg before sodium to 110.8 +/- 33.7 mL/min per kg after sodium administration (P < 0.05). The calculated or theoretical secretion rate decreased from 1470.7 +/- 404.2 to 573.5 +/- 139.5 fmol/min per kg (P < 0.025) in response to sodium. 4. We conclude that an increase in AngII metabolism and a decrease in synthesis/secretion contribute to the reduction in circulating AngII, which occurs in the first 60-90 min after sodium loading.