Early morphological and neurochemical changes of the bed nucleus of stria terminalis (BNST) in gestational protein-restricted male offspring.

BACKGROUND: The bed nucleus of the stria terminalis (BNST) is a structure with a peculiar neurochemical composition involved in modulating anxietylike behavior and fear. AIM: The present study investigated the effects on the BNST neurochemical composition and neuronal structure in critical moments of the postnatal period in gestational protein-restricted male rats' offspring. METHODS: Dams were maintained during the pregnancy on isocaloric rodent laboratory chow with standard protein content [NP, 17%] or low protein content [LP, 6%]. BNST from male NP and age-matched LP offspring was studied using the isotropic fractionator method, Neuronal 3D reconstruction, dendritic-tree analysis, blotting analysis, and high-performance liquid chromatography. RESULTS: Serum corticosterone levels were higher in male LP offspring than NP rats in 14-day-old offspring, without any difference in 7-day-old progeny. The BNST total cell number and anterodorsal BNST division volume in LP progeny were significantly reduced on the 14th postnatal day compared with NP offspring. The BNST HPLC analysis from 7 days-old LP revealed increased norepinephrine levels compared to NP progeny. The BNST blot analysis from 7-day-old LP revealed reduced levels of GR and BDNF associated with enhanced CRF1 expression compared to NP offspring. 14-day-old LP offspring showed reduced expression of MR and 5HT1A associated with decreased DOPAC and DOPA turnover levels relative to NP rats. In Conclusion, the BNST cellular and neurochemical changes may represent adaptation during development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition alters the BNST content and structure and contributes to already-known behavioral changes.

Actin cytoskeletal and functional studies of the proximal convoluted tubules after preservation.

BACKGROUND: Proximal tubule cells have specialized apical membranes with microvilli that provide an extensive surface area for unidirectional transport of solute from lumen to blood. The major structural solute component is F-actin, which interacts with transmembrane proteins, including ion transport molecules related to normal absorptive and secretory functions. Our study was to evaluate F-actin and fluid absorption (Jv) in proximal tubules after exposure to preservation solutions. METHODS: In vitro microperfusion technique and immunohistochemistry analysis. RESULTS: 1. Absorptions were similar in 1- and 24-hour-preserved tubules, as well as in fresh tubules. The exception was tubules for 24 hours in Euro-Collins solution, which did not show absorption, suggesting that it was affected. 2. Fluorescence intensity of actin tubules preserved for 1 hour in both solutions showed similar values to each other and to the control group; tubules preserved for 24 hours in both solutions were similar to each other, although statistically different than the control group and those preserved for 1 hour in Belzer (UW) solution. CONCLUSION: There were differences among groups in the distribution of F-actin; Jv values were different for 24-hour preservation in each solution, whereas fluorescence intensity was similar in both 24-hour solutions. Thus, actin cytoskeleton was not responsible for it, because 24-hour preservation in UW showed Jv results comparable to the control group.

Anxiety-like behavior and structural changes of the bed nucleus of the stria terminalis (BNST) in gestational protein-restricted male offspring.

Animal evidence has suggested that maternal emotional and nutritional stress during pregnancy is associated with behavioral outcomes in offspring. The nature of the stresses applied may differ, but it is often assumed that the mother's hippocampus-hypothalamic-pituitary-adrenal (HHPA) axis response releases higher levels of glucocorticoid hormones. The bed nucleus of the stria terminalis (BNST) is in a pivotal position to regulate the HHPA axis and the stress response, and it has been implicated in anxiety behavior. In the current study, to search whether BNST structural changes and neurochemical alterations are associated with anxiety-related behavior in adult gestational protein-restricted offspring relative to an age-matched normal protein diet (NP) rats, we conduct behavioral tests and, BNST dendritic tree analysis by Sholl analysis, associated to immunoblotting-protein quantification [11ß-HSD2, GR, MR, AT1R, 5HT1A and 5HT2A, corticotrophin-releasing factor (CRH) and CRH1]. Dams were maintained either on isocaloric standard rodent chow [with NP content, 17% casein or low protein content (LP), 6% casein] chow throughout their entire pregnancy. Here, in rats subjected to gestational protein restriction, we found: (a) a significant reduction in dendritic length and impoverished dendritic arborization in BNST neurons; (b) an elevated plasmatic corticosterone levels; and (c) associated with enhanced anxiety-like behavior when compared with age-matched NP offspring. Moreover, altered protein (11ß-HSD2, GR, MR and type 1 CRH receptors) expressions may underlie the increase in anxiety-like behavior in LP offspring. This work represents the first demonstration that BNST developmental plasticity by maternal protein restriction, resulting in fine structural changes and neurochemical alterations that are associated with modified behavioral states.

Impact of long-term high-fat diet intake gestational protein-restricted offspring on kidney morphology and function.

Emerging evidence highlights the far-reaching consequences of high-fat diet (HFD) and obesity on kidney morphological and functional disorders. In the present study, we aim to evaluate the effects of early HFD intake on renal function and morphology in maternal protein-restricted offspring (LP). LP and normal protein-intake offspring (NP) were fed HFD (LPH and NPH, respectively) or standard rodent (LPN and NPN) diet from the 8th to 13th week of age. Blood pressure, kidney function, immunohistochemistry and scanning electron microscopy were analyzed. Increased total cholesterol and low-density lipoprotein serum levels were observed in LPH offspring. The adiposity index was reduced in the (LPN) group and, conversely, increased in the NPH and LPH groups. Blood pressure was higher beyond the 10th week of age in the LPH group compared with the other groups. Decreased urinary sodium excretion was observed in LP offspring, whereas the HFD-treated groups presented a decreased urine pH in a time-dependent fashion. The LPN, NPH and LPH groups showed increased expression of type 1 angiotensin II (AngII) receptor (AT1R), TGF-ß1, collagen and fibronectin in the kidneys. Moreover, the adult fetal-programmed offspring showed pronounced effacement of the podocyte foot process associated with the rupture of cell membranes and striking urinary protein excretion, exacerbated by HFD treatment. To the best of our knowledge, this is the first study demonstrating that young fetal-programmed offspring submitted to long-term HFD intake have increased susceptibility to renal structural and functional disorders associated with an accentuated stage of fibrosis and tubular dysfunction.

Effect of captopril, losartan, and bradykinin on early steps of insulin action.

Insulin initiates its metabolic and growth-promoting effects by binding to the alpha subunit of its receptor, thereby activating the kinase in the beta subunit. This event leads to tyrosyl phosphorylation of its cytosolic substrate, insulin receptor substrate 1 (IRS-1), which in turn associates with and activates phosphatidylinositol (PI) 3-kinase. The clinical use of ACE inhibitors has been associated with increased insulin sensitivity. However, the exact molecular mechanism is unknown. In the present study, we examined the phosphorylation status of the insulin receptor and IRS-1, as well as the association between IRS-1 and PI 3-kinase in the liver and muscle of 20-month-old rats treated acutely with captopril, using immunoprecipitation with antipeptide antibodies to the insulin receptor and IRS-1, and immunoblotting with antiphosphotyrosine and anti-PI 3-kinase antibodies. Insulin stimulation increased receptor autophosphorylation to 462 +/- 253% (P < 0.05) in the liver and 697 +/- 78% (P < 0.001) in the muscle of ACE inhibitor-treated rats. There were also increases to 250 +/- 17% (P < 0.001) and 280 +/- 50% (P < 0.05) in the insulin-stimulated IRS-1 phosphorylation levels in the liver and muscle, respectively, of animals treated with captopril. The insulin-stimulated IRS-1 association with PI 3-kinase rose to 305 +/- 20% (P < 0.001) in liver and 267 +/- 48% (P < 0.05) in muscle. Losartan, an ANG receptor blocker, had no significant effect on insulin-stimulated IRS-1 phosphorylation in both tissues. The acute administration of bradykinin increased insulin-stimulated tyrosine phosphorylation of the insulin receptor and IRS-1 in the liver and muscle. These data demonstrate that ACE inhibitors modulate the early steps of insulin signaling, and that this effect may be simulated by the administration of bradykinin.

Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats.

The present study evaluated the acute effect of the intraperitoneal (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 176.6 +/- 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 163.8 +/- 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 +/- 67 microL min-1 100 g body weight-1) compared to 0.15 M NaCl-treated (890 +/- 26 microL min-1 100 g body weight-1) and captopril-treated (903 +/- 72 microL min-1 100 g body weight-1) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 +/- 0.019% compared to 0.126 +/- 0.041 and 0.66 +/- 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 +/- 0.05%) was significantly lower (P = 0.0063) than in control (0.91 +/- 0.15%) and captopril-treated rats (1.24 +/- 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

Insulin modulates leptin-induced STAT3 activation in rat hypothalamus.

Insulin and leptin have overlapping effects in the control of energy homeostasis, but the molecular basis of this synergism is unknown. Insulin signals through a receptor tyrosine kinase that phosphorylates and activates the docking proteins IRSs (insulin receptor substrates), whereas the leptin receptor and its associated protein tyrosine kinase JAK2 (Janus kinase 2) mediate phosphorylation and activation of the transcription factor STAT3 (signal transducer and activator of transcription). Here, we present evidence for the integration of leptin and insulin signals in the hypothalamus. Insulin induced JAK2 tyrosine phosphorylation, leptin receptor phosphorylation which, in the presence of leptin, augmented the interaction between STAT3 and this receptor. Insulin also increased the leptin-induced phosphorylation of STAT3 and its activation. These results indicate that insulin modulates the leptin signal transduction pathway, and may provide a molecular basis for the coordinated effects of insulin and leptin in feeding behavior and weight control.

Histologic and functional renal alterations caused by Bothrops moojeni snake venom in rats.

Acute renal failure (ARF) is the main cause of death following snake bites by Bothrops species. In this study, we investigated the morphologic and functional renal disturbances caused by Bothrops moojeni venom in rats. Renal function was assessed based on creatinine and lithium clearances and on histologic examination of renal tissue 5 hr after the intravenous administration of 0.2 mg of venom/kg and 5 hr, 16 hr, and 48 hr after 0.4 mg of venom/ kg. A venom dose of 0.4 mg/kg produced renal tubule disturbances, including acute impairment of proximal and post-proximal tubule sodium handling associated with acute tubule necrosis. The glomerular filtration rate (GFR) decreased significantly and was accompanied by severe morphologic disturbances in the renal glomeruli. These functional and morphologic findings were observed in the absence of any change in mean arterial blood pressure. The decrease in GFR was not related to the presence of fibrin deposits in the glomerular capillary loops. These results suggest an early nephrotoxic action of B. moojeni venom involving significant morphologic and functional changes similar to those observed in snakebite-induced ARF in humans.

Reduced renal sodium excretion in primary hypertensive patients after an oral glucose load.

This study was designed to determine urinary sodium excretion in response to an oral glucose load in hypertensive patients. Fifteen hypertensive patients and eighteen normotensive subjects were studied after an overnight fast and for 4 h after the ingestion of 100 g glucose. A subgroup of untreated, nonobese, primary hypertensive patients (five of the 15 hypertensive patients) became hyperinsulinemic (total area under the insulin curve [TAUC]: 33,080 +/- 3348 microU ml(-1) 120 min-1) in response to an oral glucose load compared to normotensive subjects (TAUC: 3670 < 13.731 < 23,693 microU ml(-1) 120 min-1) or to be other subgroup of normoinsulinemic hypertensive individuals TAUC: 10,221 +/- 1615 microU ml-1 120 min-1) despite a similar serum glucose concentration in both groups. A significant decrease in renal sodium excretion in the entire hypertensive group (47.1 +/- 4.7%, P < 0.019) compared to the normotensive (20.0 +/- 10.5%) subjects was also observed during the oral glucose tolerance test. Decreased renal sodium excretion was followed by a transient increase in urinary acid excretion. We speculate that the increase in insulin secretion may be responsible for the sodium-dependent increase in intracellular Ca2+, cellular H+ output and blood pressure in a subgroup of salt-sensitive patients with hypertension. New studies should be designed to identify the precise mechanisms involved in the interaction between hypertension, serum insulin-glucose levels and the magnitude of the renal tubule reabsorption abnormality.

Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats.

The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of N G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each) of male Wistar-Hannover rats weighing 200 to 250 g: 1) sham-operated vehicle-treated, 2) sham-operated L-NAME-treated, 3) denervated vehicle-treated, and 4) denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1) progressively increased arterial pressure from 108 +/- 6.0 to 149 +/- 12 mmHg (P<0.05) in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 +/- 18 to 222 +/- 59 microl min-1 100 g body weight-1 (P<0. 05) and a rise in fractional urinary sodium excretion from 0.2 +/- 0. 04 to 1.62 +/- 0.35% (P<0.05) and in sodium post-proximal fractional excretion from 0.54 +/- 0.09 to 4.7 +/- 0.86% (P<0.05). The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 +/- 0.04 to 4.5 +/- 1.6% and from 0.1 +/- 0.015 to 1.21 +/- 0.37%, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an unchanged creatinine clearance and Na+ filtered load. These results suggest that bilateral renal denervation delayed and attenuated the L-NAME-induced hypertension by promoting an additional decrease in tubule sodium reabsorption in the post-proximal segments of nephrons. Much of the hypertension caused by chronic NO synthesis inhibition is thus dependent on renal nerve activity.

Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance.

Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g). Chronic acidosis (pH 7.16 +/- 0.13) caused a sustained increase in renal fractional Na+ excretion (267.9 +/- 36.4%), accompanied by an increase in fractional proximal (113.3 +/- 3.6%) and post-proximal (179.7 +/- 20.2%) Na+ and urinary K+ (163.4 +/- 5.6%) excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 +/- 4.6 g) and pair-fed (225 +/- 3.6 g) rats compared to the controls (258 +/- 3.7 g). In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 +/- 0.05 g) compared to the other experimental groups (control, 1.46 +/- 0.05 g; pair-fed, 1.4 +/- 0.05 g). We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

Renal tubular sodium handling determined by lithium clearance in partially hepatectomized rats.

Decreased renal sodium excretion was observed 2 to 5 days after a two-thirds hepatectomy (Hx) in male Wistar-Hannover rats (200-300 g; N = 10 per group). This fall occurred after normalization of serum liver enzymes by the second day. Hepatocellular dysfunction was demonstrated by a pronounced and transient increase of about 1150% in plasma alanine aminotransferase (ALT), 500% in aspartate aminotransferase (AST), 250% in alkaline phosphatase (ALP) and in serum direct bilirubin levels, which were about six-fold higher than in sham-operated (SH) animals on the first and second days after hepatectomy. On the basis of the renal clearance of lithium in partially hepatectomized rats, there was a sustained decrease in fractional sodium excretion between the second (SH: 0.053 +/- 0.008% vs Hx: 0.023 +/- 0.008%) and fifth days (SH: 0.040 +/- 0.006% vs Hx: 0.027 +/- 0.009%) post-hepatectomy. This decrease was accompanied by a rise in the absolute (68 +/- 5.2 mumol min-1 100 g body weight-1) and fractional (85.2 +/- 1.4%) proximal sodium reabsorption rates compared to sham-operated rats (53 +/- 3.5 mumol min-1 100 g body weight-1 and 80.6 +/- 1.1%), but a return to baseline excretion levels was observed by the tenth experimental day. These changes occurred in the absence of any alterations in creatinine clearance, sodium filtered load, hematocrit and total blood volume. Further studies are required to establish the mechanisms of interaction between renal tubule sodium handling and liver function.

Effects of injection of selective adrenergic receptor antagonists into the lateral hypothalamic area on renal function.

Studies were undertaken to characterize the participation of specific alpha-1,alpha-2 and beta adrenoceptors of the lateral hypothalamic area (LHA) in the urinary excretion of sodium and potassium. Alpha-1 and alpha-2 LHA receptors were shown to participate in the regulation of renal sodium and potassium excretion. The effects of noradrenaline microinjection (30 nmol in 1 microliter) into the LHA on urinary sodium excretion (UNaV) are blocked by previous injection of the alpha-1 antagonist prazosin (4 nmol in 1 microliter) from 3.22 +/- 0.25 to 0.59 +/- 0.04 microEq min-1 100 g body weight-1. Pre-injection of yohimbine, an alpha-2 antagonist (4 nmol in 1 microliter), synergistically potentiated the action of noradrenaline on UNaV (3.22 +/- 0.25 to 4.02 +/- 0.27 microEq min-1 100 g body weight-1) and on urinary potassium excretion (UKV) (0.70 +/- 0.08 to 1.15 +/- 0.12 microEq min-1 100 g body weight-1). The beta-adrenergic blockers metoprolol (100 nmol in 1 microliter) and propranolol (100 nmol in 1 microliter) had no synergistic or antagonistic action on the sodium excretion fraction, suggesting that neither of these receptors is present in LHA. Our results indicate that natriuresis occurs even in the absence of changes in glomerular filtration rate and demonstrate an inhibitory natriuretic effect of an alpha-1 blocker (prazosin) injected into the LHA before adrenaline, while an alpha-2 antagonist (yohimbine) yielded a potentiating effect.

Inhibition of gastric acid secretion by cholinergic stimulation of the lateral hypothalamic area.

Cholinergic stimulation of the lateral hypothalamic area with carbachol (1 microgram in 1 microliter) markedly inhibited gastric acid secretion in the anesthetized rat. Inhibition was blocked by prior micro-injection of atropine (4 micrograms/microliters) into the same brain area and was accompanied by an increased sodium content in the stomach. Muscarinic receptor mediated cholinergic inhibitory influence of the hypothalamus on gastric acid secretion is suggested by these results.

Insulin resistance in essential hypertension.

To determine the possible existence of a relationship between insulin resistance and sympathetic nervous system activity in essential hypertension, we calculated the double cross index for 14 hypertensive subjects and 14 normotensive subjects submitted to the oral glucose test. Plasma glucose and insulin levels were similar in hypertensive and normotensive subjects. After glucose loading, however, both parameters were significantly higher in hypertensive subjects. Five out of 14 hypertensive patients were hyperinsulinemic. The increase in double cross index following a glucose load was significantly higher in normotensive volunteers than in hyperinsulinemic hypertensive subjects. No change in double cross index was observed in normoinsulinemic hypertensive subjects. Thus, insulin resistance, high blood glucose level, impairment of cardiac response and hyperinsulinemia are present in a significant portion of hypertensive patients. Hyperinsulinemia may contribute to hypertension by stimulating sympathetic nervous system activity, by influencing the calcium transport across the cell membrane and/or by some other mechanism.

Heterogenous insulin response to an oral glucose load by patients with the indeterminate clinical form of Chagas' disease.

This study was designed to investigate the behavior of serum glucose and insulin in response to an oral glucose load in chagasic patients with the indeterminate clinical form of the disease. Sixteen chagasic patients and 28 healthy control subjects were studied after an overnight fast and during 2 h after ingestion of 100 g glucose. There were no significant differences in serum glucose levels before and 2 h after the glucose load between chagasic and control subjects. However, in 8 chagasic patients, the total area under the insulin curve was significantly lower (2976 +/- 448 microU ml-1 120 min-1) than in the control (10123 +/- 995 microU ml-1 120 min-1) and in the remaining chagasic patients (9220 +/- 826 microU ml-1 120 min-1). These results suggest that the hypoinsulinemia of this subgroup of chagasic patients may be secondary to reduced insulin secretion and/or to increased peripheral insulin sensitivity probably related to autonomic dysfunction.

Renal water handling evaluated by lithium clearance following adrenergic and cholinergic stimulation of the lateral hypothalamic area.

Male Wistar rats weighing 230-300 g were used to characterize the participation of adrenergic and cholinergic receptors of the lateral hypothalamic area (LHA) in the control of renal water excretion. Since stimulation of adrenergic or cholinergic receptors has no effect on glomerular filtration rate, the antidiuresis and significant delay in urinary flow observed after lateral hypothalamic stimulation with carbachol (CCh) (0.036 +/- 0.005 to 0.019 +/- 0.003 microliters min-1 100 g body weight-1) and noradrenaline (Nad) (0.024 +/- 0.005 to 0.025 +/- 0.004 microliters min-1 100 g body weight-1) are secondary to an increase in distal tubular fluid reabsorption (DFR). Data are reported as means +/- SEM for ten rats in each group. Tubular water handling measured by lithium clearance demonstrated that LHA simulation with CCh (2.8 nmol in 1 microliter) and Nad (30.0 nmol in 1 microliter) leads to a significant reduction in proximal water reabsorption (CCh, 93.3 +/- 2.6 to 85.4 +/- 1.4%; Nad, 92.7 +/- 0.9 to 88.6 +/- 1.3%), with a simultaneous and significant increase in fluid reabsorption along the post-proximal nephron segments when compared to control (CNa) (CCh, 6.7 +/- 0.7 to 14.5 +/- 1.1%; Nad, 8.2 +/- 0.8 to 11.4 +/- 1.6%). These effects are blocked by muscarinic (atropine, 5 nmol in 1 microliter) and alpha-1 adrenoceptors (prazosin, 4 nmol in 1 microliter) antagonists. The results indicate the effective participation of the post-proximal nephron in the antidiuresis occurring after cholinergic and adrenergic LHA stimulation.

Effect of intracerebroventricularly injected insulin on urinary sodium excretion by cerebroventricular streptozotocin-treated rats.

Recent evidence suggests that insulin may influence many brain functions. It is known that intracerebroventricular (icv) injection of nondiabetogenic doses of streptozotocin (STZ) can damage insulin receptor signal transduction. In the present study, we examined the functional damage to the brain insulin receptors on central mechanisms regulating glomerular filtration rate and urinary sodium excretion, over four periods of 30 min, in response to 3 microl insulin or 0.15 NaCl (vehicle) injected icv in STZ-treated freely moving Wistar-Hannover rats (250-300 g). The icv cannula site was visually confirmed by 2% Evans blue infusion. Centrally administered insulin (42.0 ng/ micro l) increased the urinary output of sodium (from 855.6 85.1 to 2055 310.6 delta%/min; N = 11) and potassium (from 460.4 100 to 669 60.8 delta%/min; N = 11). The urinary sodium excretion response to icv insulin microinjection was markedly attenuated by previous central STZ (100 micro g/3 micro l) administration (from 628 45.8 to 617 87.6 delta%/min; N = 5) or by icv injection of a dopamine antagonist, haloperidol (4 micro g/3 micro l) (from 498 +/- 39.4 to 517 +/- 73.2 delta%/min; N = 5). Additionally, insulin-induced natriuresis occurred by increased post-proximal tubule sodium rejection, despite an unchanged glomerular filtration rate. Excluding the possibility of a direct action of STZ on central insulin receptor-carrying neurons, the current data suggest that the insulin-sensitive response may be processed through dopaminergic D1 receptors containing neuronal pathways.

Renal sodium handling after noradrenergic stimulation of the lateral hypothalamic area in rats.

1. The participation of special nephron segments in the renal control of sodium handling after adrenergic stimulation was investigated by determining lithium clearance in groups of 5-12 male Wistar rats (230-300 g) microinjected with noradrenaline into the lateral hypothalamic area (LHA). 2. Microinjection of noradrenaline (12.5 to 100.0 nmol/microliters) into the LHA promoted a significant decrease in proximal sodium reabsorption (controls, 86.5 +/- 1.3; 12.5, 81.4 +/- 2.0; 25.0, 72.6 +/- 2.4; 50.0, 75.4 +/- 1.8 and 100.0, 77.2 +/- 1.7%) and a dose-related increase in distal sodium reabsorption (control, 13.4 +/- 1.6; 12.5, 18.4 +/- 1,25.0, 26.9 +/- 2.9; 50.0, 24.1 +/- 2.7; 100.0, 22.1 +/- 1.9%) with no significant changes in creatinine clearance. Fractional sodium reabsorption after different noradrenaline concentrations was significantly reduced in the proximal nephron sites up to the concentration of 25.0 nmol/microliter. Beyond this concentration, a smaller but progressive increase in fractional sodium reabsorption was observed in the post-proximal segment. 3. These findings suggest an effective participation of proximal and post-proximal nephrons in natriuresis after lateral hypothalamic noradrenergic stimulation.