Macula densa derived nitric oxide in regulation of glomerular capillary pressure

Nitric oxide (NO) is produced by enzymes called nitric oxide synthases (NOS). At least three different isoforms of NOS have been identified in the kidney. This study examines the effects of selective inhibition of the inducible isoform (iNOS) and the neuronal isoform (bNOS) on the glomerular capillary pressure (PGC), through studies of the tubuloglomerular feedback (TGF) mechanism in anaesthetized rats. The proximal tubular stop-flow pressure (PSF) was measured to estimate changes in PGC obtained after activation of the TGF system by varying the loop of Henle perfusion rate with artificial ultrafiltrate including vehicle, NOS inhibition or L-arginine. Infusion of nonspecific NOS inhibition (N omega-Nitro-L-arginine) increased maximal TGF responses (delta PSF) by 84% and L-arginine decreased delta PSF by 37%. Aminoguanidine, a selective iNOS-inhibitor, failed to increase delta PSF, whereas the nonspecific NOS inhibitor methylguanidine increased delta PSF by 64%. 7-Nitro indazole (7-NI), a selective bNOS inhibitor, increased delta PSF by 57% when infused intratubularly, and intraperitoneal administration of 7-NI increased delta PSF by 78%, without any change in blood pressure. Since bNOS is exclusively located in the macula densa (MD) cells, these results confirm and strengthen the obligatory role of MD-produced NO in regulation of TGF and PGC, which has been suggested earlier. iNOS, widely expressed in the kidney, does not seem to play any important role in regulation of PGC.     

Recovery of salt appetite after lateral hypothalamic lesions: Effects of preoperative salt drive and salt intake experiences.

75 male mongrel rats were divided into lateral hypothalamic (LH)-lesion or intact control groups. The LH-lesion groups (1) had no salt experience prior to induction of lesions, (2) had experience of both salt drive and saline intake, (3) had salt drive but no saline experience, or (4) had no salt drive experience but saline intake experience. Results confirm earlier findings that preoperative salt experiences can protect the rat against the usual deficit in regulatory salt intake that follows such lesions. However, results suggest that there may be no specific feature of the preoperative salt experience that is critical for the protective effect, since both salt drive experience without concomitant salt intake experience and salt intake experience without concomitant salt drive experience were effective. (8 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of concentration presentation order and intraoral delivery on sucrose intake.

In this article, intraoral intake of an ascending concentration series of sucrose was found to plateau between concentrations of 0.3 M and 2.0 M, and thus failed to show the typical inverted U-shaped intake function found in standard intake tests. Two experiments were conducted to explain this result. In Exp 1, intraoral and standard 30-min, 1-bottle intake of ascending sucrose concentrations (0.03, 0.1, 0.3 1.0, 1.3, and 2.0 M) were compared. Sucrose intake was similar for both delivery methods. In a second experiment we examined the effect of the order of sucrose concentration presentation on the 1-bottle 30-min intake of nondeprived intact rats. An ascending concentration order of the solutions produced a significantly greater intake of concentrated sucrose solutions than did a random order. This result strongly suggests that the standard decline in sucrose intake at higher concentrations is determined not only by postoral factors but also by experiential factors (i.e., order of presentation). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low salt intake down-regulates the guanylin signaling pathway in rat distal colon

BACKGROUND & AIMS: Guanylin, an endogenous gastrointestinal peptide, causes the translocation of NaCl from interstitial fluid to the intestinal lumen. The aim of this study was to examine whether changes in dietary salt intake lead to compensatory changes in expression of the guanylin signaling pathway. METHODS: Rats received low-, normal-, or high-sodium diets for 1 week. Colonic guanylin expression was evaluated by Western and Northern blotting, rates of guanylin secretion by measuring biologically active guanylin released into the medium from colon explants, and expression of the guanylin receptor (C-type guanylate cyclase) by Northern blotting and bioassay. RESULTS: By every criterion, the low-salt diet reduced expression of guanylin to 30%-40% of the level found in control animals. Guanylin receptor expression was also decreased, although less dramatically and with a lower statistical significance. For both guanylin and guanylin receptor, the high-salt diet had no significant effect on expression. CONCLUSIONS: The data support the hypothesis that the guanylin pathway is down-regulated as an adaptive response to salt restriction.     

The influence of salt intake on glomerular count in compensatory kidney hypertrophy in rats of different ages

Drinking saline instead of water elevated the glomerular count in hypertrophied kidneys of rats uninephrectomized as adults. No changes occurred in glomerular concentration in kidney tissue indicating a more marked increase of other kidney structures. This procedure was ineffective in immature animals.     

Effects of dietary salt restriction on blood pressure and the renal vasoactive system in the congenitally bilateral hydronephrotic rat

We examined the responses on blood pressure when the renal vasoactive system such as renin-angiotensin-aldosterone system (RAAS) and kallikrein-kinin system (KKS) was activated by dietary salt restriction in the congenitally bilateral hydronephrotic rat (BHN). In a low salt diet (LS)-normotensive and normal kidney control rats after 8 weeks from initiating dietary salt restriction, the plasma sodium concentration (PNa) was retained at a level similar to that in the normal diet (ND)-control rats, and plasma renin activity (PRA), plasma aldosterone concentration (PAC) and urinary kallikrein activity (UKA) were about 1.8-, 9.4-and 1.7-fold higher, respectively, than those in the ND-control rats. In addition, LS-control rats had a significantly (p < 0.001) high systolic blood pressure (163 +/- 2.0 mm Hg) compared with that (136 +/- 5.8) of ND-control rats. These results suggest that the activated renal vasoactive system acted for not only sodium retention but also for elevation of blood pressure in LS-control rats. In LS-BHN at week 8, PNa was also retained at a nearly normal level. However, the renal vasoactive system activation for sodium retention was higher than that of LS-control rats; that is, increase of PRA, PAC and UKA were about 3.8-, 24.7-and 10.0-fold, respectively, than in ND-BHN. The higher activation of RAAS, nevertheless, does not affect blood pressure in BHN; that is, both hypertension of BHN fed LS and ND developed similarly. These findings suggest that dietary salt restriction could markedly activate the renal vasoactive system for sodium retention without elevating blood pressure in BHN different from control rats.     

Effects of lesions in the basolateral amygdala on fluid intake in the rat.

Conducted 6 experiments with 33 rats with bilateral lesions in the lateral amygdaloid region and 22 intact controls. Drinking response to hypertonic saline, a cellular thirst stimulus, and to isoproterenol, probably an extracellular thirst stimulus, was normal in lesioned Ss. The overnight water intake of the lesioned Ss was a little higher than normal. However, the lesioned Ss showed a major impairment in learning to avoid ingesting a poisonous solution of LiCl when they were thirsty and an increased preference of 25% sucrose in a 2-bottle sucrose-water test. It is concluded that the basolateral region of the amygdala is involved in the effects of previous experience on drinking and not primarily in the cellular or extracellular controls of drinking. (25 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex and sodium intake in the rat.

Female rats drink more 3% NaCl solution than do males, both when they need sodium (need-induced sodium intake or sodium appetite) and when they do not (need-free sodium intake). The sexual dimorphism of sodium intake is a secondary sexual characteristic because after castration at 1 day of age, male rats drank 3% NaCl in adulthood in a manner similar to that of females in both the need-free and need-induced state, and females given long-term neonatal testosterone drank low, malelike volumes of 3% NaCl on a daily need-free basis, but their response to sodium depletion was unchanged. This sexual dimorphism of sodium intake seems to be governed by testosterone that has been converted in the brain to estrogen because treatment of Day 1 castrated females with a nonaromatizable androgen, dihydrotestosterone, did not change either their need-free or their need-induced 3% NaCl intake. Castration in adulthood of male and female rats did not change their sodium consumption… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of salt intake on blood pressure and proteinuria in diabetes: importance of the renin-angiotensin system

Patients with hypertension and diabetes are frequently salt-sensitive. Consequently, increasing dietary salt intake results in a rise in systemic arterial pressure and an increase in proteinuria, as well as a progressive risk for developing renal injury. A difference in the renal hemodynamic response to salt appears, at least in part, to determine how the salt intake affects blood pressure. Greater dietary salt intake in salt-sensitive patients results in a blunted rise in renal plasma flow and an increase in body weight. Greater dietary salt consumption also results in a rise in glomerular filtration fraction and increasing proteinuria. Pharmacologic antagonism of the renin-angiotensin system helps restore the blunted renal plasma flow response to high salt intake and correlates with the fall in mean arterial pressure. Consequently, the pressor response to increasing dietary salt consumption in patients with diabetes and hypertension may be related to insufficient renal vasodilation, perhaps due to inadequate suppression of the renin-angiotensin system. Moreover, inadequate suppression of the renin-angiotensin system within the kidney results in an increase in efferent glomerular arteriolar tone and a rise in glomerular capillary pressure, increased proteinuria and a greater risk for renal injury. Many of the coexisting cardiovascular risk factors associated with salt sensitivity may be explainable in part by the overactivity of the renin-angiotensin system.     

Sodium depletion and maternal separation in the suckling rat increase its salt intake when adult

We identified the presence of a range of proteolytic enzyme types, normally associated with the process of general intracellular protein catabolism in mammalian tissues, in venom samples from several species of snake and from three subspecies of Russell's viper. Although levels of protease activity in venoms were in general substantially lower than corresponding levels in mammalian tissues, activity levels were comparable with several other classes of enzyme normally considered as significant venom components. Based on the protease types and relative levels of activity present in venom samples, we suggest that a possible function of these enzymes (in addition to their generally held function to increase target tissue permeability to other venom components) may be to interfere with the process of neurotransmission in target tissues, via degradation of neurotransmitter/neuromodulatory oligopeptides; this may be particularly the case for proteases such as leucyl aminopeptidase, the activity of which is greater in some venom types than in mammalian tissues. For the purposes of inter- and intra-species taxonomic classification of snakes, we would suggest that determination of a comprehensive venom protease profile may be of considerable value (particularly for subspecies differentiation) either in conjunction with or in place of more conventionally applied techniques such as analytical electrophoresis.     

Bombesin suppresses need-free and need-induced salt intake in rats.

Evaluated whether the effects of bombesin are selective for the satiation of ingestive behaviors related to energy balance or if ingestive behaviors associated with sodium balance are also suppressed by bombesin. Injections of 4 and 8 μg/kg bombesin reliably reduced need-free and sodium deficiency-induced NaCl intake in male rats. The effects of bombesin on the sodium-deficiency-induced change in taste reactivity was assessed. Injections of 4 μg/kg and 8 μg/kg bombesin had no effect on the sodium deficiency-induced shift in taste reactivity. These data indicate that bombesin suppresses NaCl intake and that bombesin does not appear to interact with gustatory sensibility in exerting its behavior-controlling action. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acamprosate and alcohol: I. Effects on alcohol intake following alcohol deprivation in the rat

Acamprosate (calcium-acetyl homotaurinate) is a new compound in the treatment of alcoholism. Its efficacy has been proven in several clinical trials and registration is now pending in most European countries. The basic mechanisms by which acamprosate elicits its anti-craving action, thereby leading to reduced relapse rates, is not known at the moment. In the present study we describe a rat model of long-term alcohol-drinking which mimics relapse behavior in human alcoholics. The effect of acamprosate was studied in this model. Wistar rats had a free choice between water and alcohol solutions of different concentrations (5, 10, 20% v/v). After two months of continuous alcohol access, rats were deprived of alcohol for three days. Following this deprivation phase, all alcohol solutions were presented again. This procedure was repeated monthly for the following six months. The rats consumed 3.5 +/- 0.3 g/kg alcohol a day. After alcohol deprivation, alcohol intake rose to 5.2 +/- 0.3 g/kg per day resulting in blood alcohol levels of 30 +/- 6 mg/dl. Interestingly, the addition of quinine to the alcohol solutions or the additional presentation of a 5% sucrose solution did not affect the alcohol-deprivation effect after eight months of this intermittent alcohol exposure. However, when acamprosate (50-200 mg/kg i.p.) was administered twice daily, alcohol-drinking following an alcohol-deprivation phase was decreased dose dependently. Given at the highest dose alcohol intake even dropped significantly below baseline drinking. Together, these results show that acamprosate effectively diminishes the alcohol-deprivation effect. Furthermore, the described model seems to be a suitable animal model to screen compounds for their anti-relapse properties and subsequently for their anti-craving action.     

Prefrontal cortex and the regulation of food intake in the rat.

Studied the postoperative regulation of food and water intake in a total of 103 male Wistar albino rats with aspiration lesions to either the medial frontal or orbital frontal projection fields of thalamic nucleus medialis dorsalis (prefrontal cortex). These projection fields proved functionally dissociable in that orbital frontal lesions impaired immediate postoperative regulation of food and water intake for up to 2 wks, while medial frontal lesions produced finickiness. Neither lesion affected response to cellular dehydration or recovery from extended deprivation. Data are consistent with data from rhesus monkeys with prefrontal lesions and differ from animals with lateral hypothalamic lesions. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of chronic intrahypothalamic infusion of insulin on food intake and diurnal meal patterning in the rat.

In Experiment 1, rats were chronically infused with insulin (2.7, 27, or 270 ng/hr) or 0.9% saline into the ventromedial (VMH), medial perifornical (PF), or lateral (LH) hypothalamus. VMH infusions of insulin caused a significant, dose-dependent decrease in food intake and body weight; PF infusion of insulin was less effective, but significant; whereas LH infusions of insulin were ineffective. In Experiment 2, rats were chronically infused with insulin (0.54 ng/hr) or 0.9% saline into the VMH, paraventricular (PVN), or posterior (PN) hypothalamic nucleus. Subjects that received VMH or PN infusions of insulin failed to regain weight lost as a result of surgery even 2 weeks after infusion; subjects that received PVN infusions of insulin regained their preoperative weights faster than did controls. All of the groups that received insulin significantly increased their daytime food intake during the infusion period and decreased their night food intake slightly; 24-hr food intake remained unchanged. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral effects of centrally administered arginine vasopressin in the rat fetus.

Arginine–8 vasopressin (AVP) was administered to rat fetuses on Embryonic Day 20 via intracisternal (IC), intrahemispheric (IH), or intrathecal (IT) injection. The IC administration of AVP promoted a 4-fold increase in motor activity, including the uncommon patterns of mouthing, licking, and facial wiping. The IH injection of AVP had little effect on fetal behavior, but IT injection resulted in pronounced increases in fetal activity, including mouthing, licking, and wiping. The IT administration of a V? antagonist blocked AVP effects, whereas IH injection potentiated AVP-induced changes in fetal behavior. The IC blockade of V? receptors suppressed facial wiping to a chemosensory fluid (lemon) and reduced oral grasping of an artificial nipple, whereas IH injection of the V? antagonist promoted facial wiping responses and increased grasping of the nipple. These data suggest that AVP may play a role in the development of responsiveness to stimuli encountered in the context of suckling. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of amphetamine and phenylethylamine on catecholamine release in the glomerular layer of the rat olfactory bulb

The purpose of this study was to examine predictors of outcome in very low birth weight (< 1500 g) children. The very low birth weight sample consisted of 68 children weighing less than 750 g at birth and 65 children weighing 750 to 1499 g at birth who had been matched to the less than 750 g birth weight children in terms of hospital of birth, age, sex, and race. Mean ages for these two groups were 6.7 and 6.9 years, respectively. Outcomes were measured in terms of tests of cognitive function, neuropsychological abilities, and academic achievement and parent and teacher ratings of child behavior and school performance. A weighted sum of the number of major neonatal medical complications (Neonatal Risk Index) provided a composite measure of biological risk. Social risks were also assessed. Results indicated that the Neonatal Risk Index was the most consistent predictor of outcomes. Even after taking social risks into account, neonatal risk predicted overall cognitive ability and other achievement, neuropsychological, and behavior outcomes. Individual neonatal complications that predicted outcomes included severe cerebral ultrasonographic abnormality, chronic lung disease, necrotizing enterocolitis, and apnea of prematurity. Research and therapy to prevent or reduce neonatal complications and amelioration of social risks are of critical importance in improving outcomes of very low birth weight.     

Alterations of salt taste perception in the developing rat.

Behavioral correlates of changing neurophysiological taste sensitivities during development were assessed with a conditioned taste aversion procedure. Young rats (age 25–30 days) avoided 0.1M monochloride salts and 1.0M sucrose reliably less than adults (age 90–105 days), but the two groups did not differ when the conditioned stimulus/stimuli (CS) was 0.1M citric acid. Analyses of generalization gradients revealed that young rats were unable to discriminate among the tastes of NaCl, NH?Cl, and KCl, whereas adults readily made such discriminations. Both age groups had similar generalization gradients when the CS was 1.0M sucrose or 0.1M citric acid. These data indicate that quantitative and qualitative aspects of salt taste perception alter with age. Furthermore, the behavioral changes noted in the present study correspond closely with previous findings from developmental studies of neuropsychological taste responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Suckling behavior and intake control in the developing rat pup.

Studied the behavioral development of suckling and intake control in 2 experiments with Charles River CD strain rat pups. Ss were observed at the initiation, during the course, and at the termination of suckling from their anesthetized mothers. Diet was delivered intraorally through a fine tongue cannula which enabled control of timing and volume. The control of diet intake and the behavior at termination of suckling showed correlated changes from 5 to 20 days of age. When deprived of suckling (and food and water) for 8 hr, 5- and 10-day-old Ss consumed large volumes of diet (10% of body weight or greater) and terminated suckling only in the presence of extreme gastrointestinal filling. These Ss were immediately lethargic and slept after intake termination. Five-day-old Ss persisted in reattaching to the nipple when manually stimulated; 10-day-old Ss eventually refused to reattach. In contrast, 20-day-old Ss consumed more moderate volumes of diet (5% of body weight). These Ss also remained awake for a period after feeding and engaged in the exploratory and grooming activities characteristic of adult rats at the termination of feeding. These observations demonstrate major changes in suckling behavior during development. They suggest that intake control processes shift from indirect to direct and become more effective and specifically food intake related in older pups. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)