Comparison of the natriuresis and chlorures is associated with glomerular hyperfiltration induced by atrial natriuretic factor or glucagon

The impact on renal sodium chloride reabsorption of an acute increase in glomerular filtration rate (GFR) induced by atrial natriuretic factor (ANF) or glucagon was examined in the conscious rat. These hormones have no direct effect on proximal solute transport and have opposite effects on distal transport. ANF and glucagon increased GFR to a comparable extent (2.0 ± 0.2 to 3.5 ± 0.4 ml/min, p<0.01, and 1.9 ± 0.1 to 3.3 ± 0.1 ml/min, p<0.001, respectively). While most (95–97%) of the increment in filtered sodium chloride was reabsorbed, a small portion (3–5%) escaped tubular reabsorption. Absolute sodium and chloride urinary excretion rates increased similarly in response to each hormone, by two- to three-fold. Slightly imperfect load-dependent sodium chloride reabsorptive response by the nephron, despite opposite direct effects on distal nephron transport, may account for the observed natriuresis and chloruresis associated with the acute glomerular hyperfiltration induced by ANF or glucagon administration.     

Effect of vasoactive substances on natriuresis induced by atrial natriuretic peptide in isolated perfused rat kidneys

We studied the interaction between synthetic atrial natriuretic peptide (ANP) and various vasoactive substances, which included isoproterenol (ISO), aminophylline (AMI), and dibutyryl cyclic AMP (dBcAMP) as vasodilators, and angiotensin II (AII) and norepinephrine (NE) as vasoconstrictors, and prazosin as an alpha-blocker in isolated perfused rat kidneys (IPK). When 10(-9) mol of ANP was administered in 75 ml of a perfusate, the renal vascular resistance (RVR) was transiently decreased for 5 min, and increased thereafter. Simultaneously, ANP increased the glomerular filtration rate (GFR), urine flow (UV), absolute Na excretion (UNaV) and absolute K excretion (UKV). All of the above mentioned effects of ANP were significantly inhibited by administering ISO, AMI or dBcAMP. On the other hand, the administration of AII and NE significantly enhanced the increases in UV and UNaV and the fractional excretion of Na induced by ANP, although AII and NE had no influence on the changes in RVR and GFR induced by ANP. Prazosin did not modify the renal effects of ANP. These results suggest that the natriuretic effect of ANP is inhibited by agents that increase cyclic AMP in vascular smooth muscle cells. It is also suggested that the natriuretic effects of ANP can be explained by an increase in GFR and changes in intrarenal hemodynamics, rather than by the direct effect of ANP on renal tubules.     

Association of the atrial natriuretic factor receptor with guanylate cyclase in solubilized rat glomerular membranes

The elution profile of solubilized rat glomerular membranes from a gel filtration column showed two peaks of 125I-ANF (atrial natriuretic factor) binding (367 +/- 21, 156 +/- 12 KDa). Over 85% of the total binding for the extract was in the 367 KDa peak. Guanylate cyclase activity was correlated with 125I-ANF specific binding. ANF activation of guanylate cyclase was also observed. As observed previously with particulate membrane, Scatchard-analysis of ANF binding data with the solubilized extract was consistent with a two-site model. Both affinities (Kd's), 4 pM and 1 nM, are within the range of blood concentrations reported for ANF. These observations suggest that most rat glomerular ANF receptors are large molecular complexes coupled with guanylate cyclase in the 300-350 KDa size range.     

Mechanisms of neonatal increase in glomerular filtration rate

To investigate the mechanisms responsible for the neonatal increase in glomerular filtration rate (GFR), renal function studies (whole kidney and micropuncture) were carried out in anesthesized fetal sheep (133-140 days gestation; term = 150 days) and lambs (12-18 days). Fetuses were delivered and placed in a water bath (39.5 degrees C), keeping the umbilical cord moist and intact. Lambs were studied on a thermostatically controlled heating pad. Animals were prepared for either blood flow studies or micropuncture measurements. Expected differences in blood composition and cardiovascular and renal function were observed between fetuses and lambs, and values obtained for most variables were similar to those measured in chronically catheterized unanesthetized animals. Fetal GFR was much lower than that of lambs (0.20 vs. 0.62 ml.min(-1).g kidney(-1), P < 0.001). Free-flow, stop-flow, and net filtration pressures (NFP) were lower in the fetuses than the lambs (NFP 20.8 vs. 23.8 mmHg, P < 0.001), as was the calculated ultrafiltration coefficient (0.014 vs. 0.022 ml.min(-1).g(-1).mmHg(-1), P < 0.001). Thus, we conclude that rises in both net filtration pressure and the ultrafiltration coefficient contribute to the large increase in GFR between fetal life and approximately 2 wk after birth.     

The mechanism of polyethylene glycol-induced natriuresis in rats: role of atrial natriuretic hormone

A putative role of atrial natriuretic hormone (ANH) in a polyethylene glycol (PEG) 200-induced natriuresis was examined in conscious Wistar rats. Low molecular weight PEG 200 (0.5 or 1.0 ml/100g body weight) was orally administered to rats by gavage. Urine was collected during a 3 hr test period and blood was obtained at the end of each experiment for measurement of ANH, PRA, clearance studies and for indirect indices of plasma volume. Urinary excretion of sodium and volume increased while plasma ANH concentrations were markedly decreased in a dose-related manner following PEG 200 administration. The osmotic clearance was also elevated following PEG 200 administration. No significant change was observed in any of the parameters following high molecular weight PEG 8000. The observed decrease in ANH was associated with an apparent contraction of plasma volume despite the increased serum osmolality. These data indicate that the ANH inhibitory influence of the decreased plasma volume takes precedence over the stimulatory effect of the hyperosmolality and the latter is primarily responsible for the increased osmotic clearance and natriuresis observed in this model.     

Role of natriuretic factor in central nervous system (CNS)-induced natriuresis

The presence of a natriuretic factor in the plasma of rats in which a 350 mM Na (high Na) artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle was tested. Blood was obtained from control rats and rats which received an infusion of high Na CSF intraventricular (IVT) for 15 min. The plasma was incubated for 30 min at room temperature, acidified, placed in a boiling-water bath, and then centrifuged. The plasma supernate was assayed for natriuretic activity in pentobarbital anesthetized bioassay rats. Sodium excretion increased 6.5 +/- 1.1 mueq/kg X min in rats which received an infusion of a control saline solution, 13.3 +/- 3.2 mueq/kg X min in rats which received infusion of control plasma supernates, and 32.1 +/- 8.3 mueq/kg X min in those rats which received plasma supernates from rats infused with high Na CSF IVT. Blood pressure was unchanged in all groups. The increment in sodium excretion elicited by plasma supernate from the high Na IVT group was significantly greater than that elicited by either control saline solution or control plasma extracts. Therefore, it is concluded that a heat-stable and nonpressor natriuretic factor is present in the plasma of rats infused IVT with high Na CSF.     

Estimating glomerular filtration rate in diabetes using serum cystatin C

Chronic kidney disease (CKD) is a major public health problem, especially for people with diabetes. Not only is it a risk factor for end-stage renal disease (ESRD) but it is also a major cardiovascular disease (CVD) risk factor. Methods that accurately and simply estimate glomerular filtration rate (GFR) are therefore needed to optimise the detection and management of CKD in people with diabetes. One of the main failures of commonly used creatinine-based methods for estimating renal function is that they lack applicability across the full range of GFR values and underestimate GFR levels >60 mL/min/1.73m(2). Methods for accurately estimating an early pathological decline in GFR (i.e. ΔGFR >3.3 mL/min/year before reaching a GFR <60 mL/min/1.73m(2)) are especially needed as appropriate interventions have been shown to retard progression to ESRD and reduce CVD risk in people with diabetes. In contrast, recent studies have suggested that estimates of GFR based on serum cystatin C concentration might provide a simple and accurate method for detecting and monitoring an early decline in renal function.     

Degradation of atrial natriuretic factor in the rat.

The biologically active circulating form of atrial natriuretic factor (ANF) in the rat is the 28-amino-acid peptide ANF-(Ser-99-Tyr-126). Degradation of this peptide in vivo as well as in vitro, in whole blood, in plasma and by the isolated mesenteric artery was investigated. Studies in vivo in the rat demonstrated that the elimination and degradation of ANF was extremely fast: within 3 min more than 95% of the injected immunoreactive material was eliminated from circulation. The production of a short C-terminal peptide was detected on injection of 125I-ANF-(Ser-99-Tyr-126) into the rat. This peptide increased proportionately with incubation time. Experiments in vitro in the presence of whole blood or plasma did not cause any major destruction of ANF even after incubation for 60 min. After this prolonged incubation in plasma, ANF-(Ser-99-Tyr-126) was partially converted into ANF-(Ser-103-Tyr-126), a less potent peptide. Isolated mesenteric-artery preparation appeared to degrade ANF in a manner very similar to the system in vivo. These results suggest that degradation of ANF may occur either after internalization in the vascular cells or by a membrane-bound enzyme in the vasculature.     

The cellular localization of increased atrial natriuretic peptide mRNA and immunoreactivity in diabetic rat kidneys.

Increased intrarenal atrial natriuretic peptide (ANP) mRNA expression has been reported in several disorders. To further investigate the action of renal ANP, we need to elucidate the exact site of its alteration in diseased kidneys. ANP mRNA and ANP were detected by in situ hybridization and immunohistochemistry in the kidneys from five normal and five diabetic rats. Renal ANP mRNA in eight normal and nine diabetic rats was measured by RT-PCR with Southern blot hybridization. In normal and diabetic rats, the distribution of ANP mRNA and ANP-like peptide was mainly located in proximal, distal, and collecting tubules. However, diabetic rats had significant enhancement of ANP mRNA and ANP-immunoreactive staining in the proximal straight tubules, medullary thick ascending limbs, and medullary collecting ducts. ANP mRNA in the outer and inner medulla of nine diabetic rats increased 5.5-fold and 3.5-fold, but only 1.8-fold in the renal cortex. This preliminary study showed that ANP mRNA and ANP immunoreactivity in proximal straight tubules, medullary thick ascending limb, and medullary collecting ducts apparently increased in diabetic kidneys. These findings imply that ANP synthesis in these nephrons may involve in adaptations of renal function in diabetes.     

Role of nitric oxide on atrial natriuretic peptide release induced by angiotensin II in superfused rat atrial tissue

The present study investigated the role of nitric oxide (NO) on atrial natriuretic peptide (ANP) release stimulated by angiotensin II (Ang II) (10(-7) M) in superfused sliced rat atrial tissue. The use of N(G)-nitro-L-arginine methyl ester (L-NAME) at 10(-4) M, an inhibitor of nitric oxide synthase did not modify basal ANP release. In presence of Ang II (10(-7) M), we observed that L-NAME enhanced ANP secretion induced by Ang II. Furthermore, cGMP levels increased significantly in the presence of Ang II and was attenuated by L-NAME. On the other hand, the perfusion of 8 bromo-cGMP (10(-5) M) with Ang II reduced the effect of this octapeptide on ANP secretion. Secondly, we evaluated the effect of authentic NO on ANP release and observed that perfusion of NO reduced significantly the effect of Ang II on ANP release. We propose that the effect of Ang II on ANP secretion was modulated by NO likely via cGMP pathway.