Operated Control Rats Research Articles

Гастропротективна дія кріоконсервованого екстракту плаценти за профілактичного режиму застосування

Introduction. Timely treatment and prevention of peptic ulcer of the stomach and duodenum is not only medical but also social. As a potential gastroprotective agent, our attention was drawn to the cryopreserved extract of human placenta, because the literature convincingly demonstrated that this cryoextract eliminates the ulcerogenic action of nonsteroidal anti-inflammatory drugs, which has a mechanism similar to peptic ulcer disease. The aim of the study was to characterize the gastroprotective activity of cryopreserved placenta extract under the prophylactic regimen of use in the model of ethanol-prednisolone gastric lesions in rats. Materials and methods. The study was performed on 28 male rats weighing 200–220 g. Gastric lesions in rats were simulated by intragastric single administration of prednisolone (20 mg/kg) dissolved in 80.0% ethanol (0.6 ml/100 g body weight). Cryoextracts of the placenta were administered intravenously in a prophylactic mode – 1 time per day for 5 days before the introduction of ethanol-prednisolone mixture. In 24 h. after administration of the mixture, rats were removed from the experiment and the size of the stomach (bloating) and the presence of adhesions with adjacent organs were evaluated macroscopically by the following criteria: erosions and hemographies, hyperemia, edema and mucosal fold disorders. For each group, the percentage of experimental animals was calculated according to these characteristics and the average value of their severity. The values of the ulcer index were calculated for each group. Research results and their discussion. The introduction of ethanol-prednisolone mixture causes erosive ulcerative lesions of the gastric mucosa in 100% of rats The introduction of cryoextract placenta significantly reduced the damaging effect of ulcerogenic mixture on the mucous membrane, advice on the performance of control rats. The severity of antiulcer activity of the studied cryoextract in the prophylactic mode of use is statistically significantly (p<0.05) exceeds the similar effect of esomeprazole. Conclusions. Prophylactic five-day administration of cryopreserved placenta extract is accompanied by a statistically significant (p<0.05) marked gastroprotective effect in a model of ethanol-prednisolone gastric lesions in rats.

Disconnection of the perirhinal and insular cortices severely disrupts taste neophobia

It is well known that the perirhinal (Prh) and insular (IC) cortices are reciprocally connected, mainly through ipsilateral projections. Although some studies have demonstrated that excitotoxic lesions to these regions, each separately, disrupt taste neophobia, it is not yet known whether the two regions have functional interactions with one another. To find out if they form a functional unit, we examined the effects of crossed excitotoxic lesions to the Prh and the contralateral IC (contralateral group). This group's performance was compared to that of rats with ipsilateral Prh and IC lesions (ipsilateral group) and to that of control-operated rats. All the animals received a 0.3% saccharin solution for fifteen minutes on five consecutive days. Rats with contralateral Prh-IC lesions drank significantly higher amounts of saccharin than the other groups during the first encounter with the novel taste, indicating a disruption in neophobia. However, the lesions did not disrupt attenuation of neophobia, with the contralateral group reaching asymptote in trial 2 and the rest of the groups after 3–5 days of exposure to the saccharin. These findings suggest that both Prh and IC play a necessary role in taste neophobia. Additionally, the two cortices function interdependently and their interaction is critical for normal expression of taste neophobia.

Refining surgical models of osteoarthritis in mice and rats alters pain phenotype but not joint pathology.

The relationship between osteoarthritis (OA) structural change and pain is complex. Surgical models of OA in rodents are often rapid in onset, limiting mechanistic utility and translational validity. We aimed to investigate the effect of refining surgical small rodent models of OA on both joint pathology and pain behaviour. Adult male C57BL/6 mice (n = 76, 10–11 weeks of age at time of surgery) underwent either traditional (transection of the medial meniscotibial ligament [MMTL]) or modified (MMTL left intact, transection of the coronary ligaments) DMM surgery, or sham surgery. Adult male Sprague Dawley rats (n = 76, weight 175-199g) underwent either modified meniscal transection (MMNX) surgery (transection of the medial meniscus whilst the medial collateral ligament is left intact) or sham surgery. Pain behaviours (weight bearing asymmetry [in mice and rats] and paw withdrawal thresholds [in rats]) were measured pre-surgery and weekly up to 16 weeks post-surgery. Post-mortem knee joints were scored for cartilage damage, synovitis, and osteophyte size. There was a significant increase in weight bearing asymmetry from 13 weeks following traditional, but not modified, DMM surgery when compared to sham operated mice. Both traditional and modified DMM surgery led to similar joint pathology. There was significant pain behaviour from 6 weeks following MMNX model compared to sham operated control rats. Synovitis was significant 4 weeks after MMNX surgery, whereas significant chondropathy was first evident 8 weeks post-surgery, compared to sham controls. Pain behaviour is not always present despite significant changes in medial tibial plateau cartilage damage and synovitis, reflecting the heterogeneity seen in human OA. The development of a slowly progressing surgical model of OA pain in the rat suggests that synovitis precedes pain behaviour and that chondropathy is evident later, providing the foundations for future mechanistic studies into the disease.

I–2 Systemic Effect of LIPUS on B-TCP-(tri-calcium-phosphate) Ceramic Discs Subcutaneously Implanted in the Dorsal Aspect of Rat

Objective: It is essential to have sufficient numbers of cells for bone regeneration. We previously reported that LIPUS exposure to rodent fractured femurs or sockets of extracted teeth recruited cells from sites remote to the lesion through peripheral blood vessels (Kumagai, Takeuchi et al, J Orthop Res 2012 and Hidaka et al, Int J Anal Bio-Sci 2015). In the present study, we tried to show LIPUS exerted its anabolic action systemically on tricalcium phosphate (β-TCP) discs implanted in the back of rats, which were not directly treated with LIPUS. Materials and Methods: Four pairs of male Sprague Dawley rats were operated on as previously described. A week later, 3 β-TCP discs were implanted in the dorsal aspect of sham operated control rats and the experimental rats. On and following the day of implantation, the 2 discs closer to the rat head only in one of the pair were exposed to LIPUS every 24 hours for 2 weeks as described. Results and Discussion: Except in one rat, which showed enlarged spleen and adrenal body, no abnormality was found. Body weight, histology, and transfer of injected fluorescence-conjugated protein from one to the other rat suggested the operation was successful. In the β-TCP discs of LIPUS-untreated side rats, we observed invaded cells and blood vessels present in numbers between those of the LIPUS-exposed and the control rats. Real-time PCR and immunohistochemistry analysis also showed consistent results. Given these findings, the systemic effect of LIPUS may be more influential than we used to assume.

The Neuroprotective Effect of Kefir on Spinal Cord Ischemia/Reperfusion Injury in Rats.

ObjectiveThe main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuroprotective effects of kefir on spinal cord ischemia injury in rats.MethodsRats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores.ResultsThe kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-1α and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05).ConclusionOur study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

Abstract 189: Omeprazole Decreases Chronic Antihypertensive Effects of Sodium Nitrite

Introduction: Recent studies showed that sodium nitrite decreases blood pressure (BP) in two kidney, one clip (2K1C) hypertension, probably as a result of nitrite being converted into nitric oxide in the acid environment of the stomach. This study aimed at examining whether increasing gastric pH with omeprazol reduces the chronic antihypertensive effects of nitrite. Methods: 2K1C hypertensive and sham operated control rats were treated with omeprazole (10mg/Kg; i.p.) or vehicle and sodium nitrite (15mg/Kg; gavage) or saline for two weeks. Systolic BP (SBP) was measured by tail pletismografy weekly. Circulating nitrite levels were measured by chemiluminesce and gastric pH was measured with an electrode. The results were analyzed by two-way ANOVA. The results are show as mean ± standard deviation. Results: 2K1C rats were hypertensive two weeks after surgery (SBP=180±17 mmHg). After 4 weeks of treatment, nitrite exerted antihypertensive effects in rats treated with vehicle (SBP=161±23 mmHg versus 200±29 mmHg, respectively, in the 2K1C+nitrite and in the 2K1C+saline groups; P&lt;0.05). However, nitrite exerted no antihypertensive effects in 2K1C rats treated with omeprazole (SBP=200±34 mmHg; P&gt;0.05 versus 2K1C+saline group). We found no significant differences among the sham operated groups. Similar increases in plasma nitrite concentrations were found when animals treated with nitrite and omeprazol were compared with those treated with nitrite and vehicle (8.5±4.1 versus 5.2±3.6 μM, respectively; P&gt;0.05). Omeprazole increased gastric pH in all animals treated with this drug (P&lt;0.05). Conclusion Treatment with omeprazole blunts the chronic antihypertensive effects of sodium nitrite in 2K1C rats. However, this effect is probably not associated with significant differences in plasma nitrite concentrations.

Inhibition by folic acid of tumor necrosis factor alpha and apoptosis following normothermic ischemia-reperfusion

Folate is necessary for the production and maintenance of new cells and important during periods of rapid cell division and growth. Tumor necrosis factor-alpha (TNF-alpha) is known as a stimulant of apoptotic cell death. The present study was aimed to evaluate the efficacy of folic acid (CAS 59-30-3) in prevention of apoptosis by inhibiting TNF-alpha action in ischemia-reperfusion (I/R) induced liver injury. Eighteen Wistar rats were subjected to 1 h of hepatic ischemia followed by 3 h reperfusion and were divided into sham-operated control Group (I) (n = 6), ischemia and reperfusion group administered 0.9% saline (5 ml/kg, p.o.) for 7 days (II) (n = 6), folic acid treated group (1 mg/kg body weight/treated daily by oral route for 7 days before induced ischemia-reperfusion maneuver) (III) (n = 6). Hepatic damage in rats was assessed in terms of serum alanine transaminases and aspartate transaminases. TNF-alpha concentration was measured in serum by enzyme linked immuno assay. Necrosis and apoptosis were measured by flow cytometry and fluorescence microscopy. Apoptotic marker Bcl-2 gene expression was measured by reverse transcriptase polymerase chain reaction (RTPCR) and Western Blot Analysis. Pathological changes were measured by transmission electron microscopy (TEM). Serum alanine transaminase (ALT), aspartate transaminase (AST) and TNF-alpha concentration increased significantly (p < 0.05) in rats with I/R induced injury as compared to sham operated control rats. Pretreatment with folic acid effectively counteracted the alternation in hepatic enzymes. TEM, expression of Bcl-2 protein and flow cytometry studies confirmed the restoration of cellular normalcy and accredits the cytoprotective role of folic acid against I/R induced hepatic injury. The present study demonstrated that elevated TNF-alpha activity directly related to apoptosis and folic acid inhibits apoptosis by inhibiting the action of TNF-alpha.

POSSIBLE ROLE OF LOW LEVEL LASER THERAPY ON BONE TURNOVER IN OVARIECTOMIZED RATS

The aim of this study was to assess the effect of low level laser therapy (LLLT) on bone turnover markers in ovariectomized rats. Thirty adult female albino rats were divided into three groups; Group 1: 10 sham- operated control rats; Group 2: 10 bilaterally ovariectomized rats (OVX); Group 3: 10 OVX rats exposed to LLLT. LLLT was applied on the neck and shaft of femur, five times per week for 8 weeks. The dose applied on each point was 1000 Hertz, 5 Watts for 30 seconds with a total dose of 15 mJoule/cm². At the end of experiment, blood samples were collected and sera were separated for determination of serum calcium (Ca), inorganic phosphorus (Pi), osteocalcin and alkaline phosphatase (ALP). In addition, a 24 hour urine sample was also collected from each rat for the determination of urinary calcium, phosphorous and deoxypyridinoline (U-DPD)/creatinine. Significant increase in serum Ca, Pi , ALP, osteocalcin and significant decrease in U-DPD/creatinine in LLLT exposed group was found as compared to the other two groups. Bone morphological findings revealed the increase in calcium deposition and alkaline phosphatase of femoral bones in LLLT exposed group as compared to sham-operated and OVX rats. The software image analysis showed increased osteoblast numbers, decreased osteoclast numbers and increased compact bone thickness in LLLT exposed group. Significant positive correlations was obtained between osteoblast numbers and serum Ca , Pi, ALP and osteocalcin in LLLT exposed group ,while a significant negative correlation was noticed with U-DPD. The use of LLLT was found effective in enhancing bone formation and decreasing bone resorption in the osteoporotic OVX rats. Further studies are necessary to investigate the effect of different parameters of LLLT as wave length, duration and also numbers of sessions. The potential use of LLLT in postmenopausal women with osteoporosis is needed to be verified.

A high molecular weight protein Bengalin from the Indian black scorpion ( Heterometrus bengalensis C.L. Koch) venom having antiosteoporosis activity in female albino rats

This study reports the presence of a high molecular weight protein (Bengalin) from the Indian black scorpion ( Heterometrus bengalensis) venom having antiosteoporosis activity in experimental osteoporosis developed in female albino Wister rats. Bengalin was purified through DEAE-cellulose ion exchange chromatography and high performance liquid chromatography. The molecular weight of the Bengalin was found to be 72 kDa and the first 20 amino acid sequence was found to be G-P-L-T-I-L-H-I-N-D-V-H-A-A/R-F-E-Q/G-F/G-N-T. Bengalin exhibited significant antiosteoporosis activity in experimental female rats, which was confirmed through analysis of urine Ca 2+, PO 4 3−, CRE & OH-P. Bengalin (3 μg and 5 μg/100 g rat/i.p.) antagonized osteoporosis by restoring urinary Ca 2+, PO 4 3−, CRE and OH-P, serum/plasma Ca 2+, PO 4 3−, ALP, TRAP, PTH, T 3, TSH, Osteocalcin, IL1, IL6 and TNF α and bone minerals Ca 2+, P, Mg 2+, Zn 2+, Na +, as compared with the sham operated control rats. Bone minerals density of osteoporosis female rats was improved due to Bengalin, observed through DEXA scan. Subacute toxicity studies in male albino mice, Bengalin showed cardiotoxicity. In vivo experiments, Bengalin showed cardiotoxicity on isolated guinea pig heart, guinea pig auricle, and neurotoxicity on isolated rat phrenic nerve diaphragm preparation. Further detail studies on the toxicity, antiosteoporosis and structural identity of Bengalin are warranted.

The effects of beta-adrenergic blockade on the hypothalamic and neurohypophysial vasopressin and oxytocin content in pinealectomized male rats.

Pinealectomized (PX), sham-operated and non operated control rats were injected intraperitoneally (i.p.), once daily at 8.00 over five days, with: (a) 0.9% sodium chloride, (b) propranolol hydrochloride in a dose of 10 mg/kg (= 0.1 ml solution per 100 g b.w.). Three hours following the last injection the animals were decapitated and the content of vasopressin and oxytocin was bioassayed in the hypothalamus and neurointermediate lobe. PX was followed by known decrease of both vasopressin and oxytocin in the hypothalamus and neurohypophysis. In rats not-PX propranolol did not change the vasopressin and oxytocin content in the hypothalamus and neurointermediate lobe. In PX-rats, treatment with propranolol resulted in a distinct increase of the vasopressin in the neurohypophysis. It may be therefore supposed that the beta-adrenergic transmission is in some way involved in the regulatory mechanisms of pineal-neurohypophysial functional relationship.

Experimental osteoporosis induced in female albino rats and its antagonism by Indian black scorpion ( Heterometrus bengalensis C.L.Koch) venom

The present study was designed to explore the antiosteoporosis activity of the Indian black scorpion ( Heterometrus bengalensis) venom on experimental osteoporosis female albino rats. Sham operated control rats were designated as Gr I, Gr II animals served as osteoporosis control, Gr III osteoporosis rats were treated with SV (1/25th of MLD), Gr IV osteoporosis rats were treated with 1/50th of MLD of SV and Gr V osteoporosis rats were treated with standard (calcium and vit-D3). As compared with the Gr I rats, the Gr II rats showed typical osteoporosis changes in increased of urinary Ca 2+, PO 4 3−, CRE, OH-P levels, serum/plasma Ca 2+, PO 4 3−, TRAP, IL1, IL6, TNFα and PTH level, bone Ca 2+, PO 4 3−, Mg 2+, Zn 2+ and decreased level of serum/plasma ALP, EST and PTH, bone Na +. In Gr III, Gr IV and Gr V rats, the osteoporosis changes of urine, serum and bone, were significantly restored as compared with the Gr II rats. The bone dimensions, morphology and histological changes observed in Gr II rats were restored in Gr III, Gr IV and Gr V rats. This study confirms that the Indian black scorpion venom may influence bone remodeling process by stimulating bone formation and reducing bone resorption process of osteogenesis.

Noise exposure at young age impairs the auditory object exploration behavior of rats in adulthood

Environment noise is ubiquitous in our daily life. The aim of the present study was to determine the effect of postnatal exposure to moderate-level noise on the auditory object exploration behavior of adult rats by comparing the ability of three groups of rats to locate a sound source in a water maze. Two groups of rats, either in the critical period of hearing development or in adulthood, were exposed to 80 dB SPL interrupted white noise for 8 h per day for two weeks. The control group of rats was not exposed to the noise. The ability of the rats to locate a hidden platform that was situated near a sound source in a water maze was tested starting on postnatal day 77. A continuous improvement in the performance of control rats and rats exposed to noise in adulthood was observed during training, whereas rats exposed to noise at a young age exhibited a significantly worse performance. These findings indicated that long-term exposure of young rats to moderate-level noise caused significant impairment of their auditory object exploration behavior compared to exposure of adult animals to the same moderate-level noise.

The divergent role of epoxyeicosatrienoic acids in the regulation of renal function in normotensive and two‐kidney one‐clip Goldblatt hypertensive rats

To assess the renal function in anesthetized Hannover Sprague‐Dawley rats with induced renovascular hypertension for 27 days (2K1C) and normotensive sham operated control rats during acute inhibition of epoxyeicosatrienoic acids (EETs) generation in the kidney, epoxygenase inhibitor, methylsulfonyl‐6‐(2‐propargyloxyphenyl) hexanamide (MS‐PPOH, 12 μmol/L), was continuously administered directly into the nonclipped kidney at a rate 0.3 mL/hour for over 60 minutes. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined by Inulin and PAH clearance, respectively.Basal renal function of the nonclipped kidney was not different (GFR 0.79±0.07 vs. 0.74 ±0.03 mL/min/g; RPF 2.03±0.09 vs. 2.04 ±0.13 mL/min/g and sodium excretion 1.85±0.31 vs. 1.51 ±0.29 μmol/min/g) in hypertensive 2K1C rats (n=8) compare to sham operated control rats (n=8). Although administration of MS‐PPOH caused significant decreases in GFR (15±3%), RPF (18±4%) and sodium excretion (42±9%) in sham operated rats, MS‐PPOH did not significantly alter renal function in the nonclipped kidney of 2K1C rats.These data further support the notion that EETs contribute in modulation of renal vasodilatation and natriuresis which might be impaired in 2K1C rats due to deficiency of intrarenal EETs in this hypertensive model.

A METHOD FOR PRODUCING OVERACTIVE BLADDER IN THE RAT AND INVESTIGATION OF THE EFFECTS OF GABAergic RECEPTOR AGONISTS AND GLUTAMATERGIC RECEPTOR ANTAGONISTS ON THE CYSTOMETROGRAM

We induced radio frequency (RF) lesions in the neuronal pathway leading from the forebrain to the pontine micturition center (PMC) to produce a rat model of bladder overactivity. We studied the effects of gamma-aminobutyric acid agonists (diazepam and baclofen) and glutamate receptor antagonists (MK-801 maleate and GYKI52466 [1-(4-aminophenyl-D-4-methyl-7,8 methylenedioxy-5H-2,3-benzodiazepine] hydrochloride) on the cystometrogram and developed a possible explanation of the neuronal mechanisms underlying RF lesion induced bladder overactivity. Seven-week-old male Sprague-Dawley rats were anesthetized with sodium pentobarbital and RF lesions were produced in the nuclei basalis. Five days later bladder contractions were induced by infusing fluid into the bladder and cystometrograms were measured in conscious rats. The micturition interval (MI) in rats subjected to RF lesioning was significantly shorter than that in sham operated control rats. Diazepam (0.1 and 1 mg/kg intraperitoneally), baclofen (1 mg/kg intravenously) and MK-801 (0.1 and 1 mg/kg intravenously) did not change or shortened MI in control rats but it prolonged MI in lesioned rats. GYKI52466 (0.5 and 1 mg/kg intravenously) weakly prolonged MI in lesioned rats. We consider that RF lesioning causes interruption of the inhibitory GABAergic neurons that lead from the forebrain to the PMC. This results in the activation of N-methyl-D-aspartate receptors in the PMC that are involved in the facilitation of voiding.

Immortalized Neural Stem Cells Transplanted Into the Injured Spinal Cord Promote Recovery of Voiding Function in the Rat

Bladder dysfunction is a serious consequence of spinal cord injury. Cellular transplantation into the injured spinal cord can promote axonal growth and functional recovery. We investigated whether EG6 immortalized neural stem cells transplanted into the injured spinal cord of the rat contribute to a recovery of lower urinary tract function. The spinal cord of 14 female Wistar rats was injured by compression. In 7 rats 9 days after spinal cord injury BrdU (5-bromo-2'-deoxyuridine) labeled EG6 cells were transplanted into the injured spinal cord. Seven operated (OP) control rats received intraspinal injections of culture medium alone. Voided volume per micturition was assessed in a metabolic cage for 24 hours on days 14 and 28 after transplantation. On day 28 saline was infused via a catheter inserted into the bladder and intravesical pressure was measured in OP control and EG6 transplant rats. EG6 cells identified by BrdU immunocytochemistry survived in the injured spinal cord. Voided volume per micturition significantly increased in EG6 transplant rats by day 28 after transplantation. Micturition pressure significantly decreased in EG6 transplant rats compared with OP controls. Although voided volume did not differ, post-void residual urine was significantly less in EG6 transplant than in OP control rats. Thus, voiding efficiency was significantly greater in EG6 transplant rats compared with OP controls. There was no difference in the incidence of detrusor hyperreflexia. Transplanted EG6 cells survived in the injured spinal cord and had beneficial effects on the recovery of voiding function after spinal cord injury in the rat.

Retinoid Agonist Isotretinoin Ameliorates Obstructive Renal Injury

Interstitial fibrosis is a major cause of end stage renal failure. Retinoids, which are involved in tissue repair and fibrosis, inhibit inflammatory and proliferative pathways. Therefore, we studied the dose dependent effects of the retinoid receptor agonist isotretinoin 13-cis retinoic acid in the unilateral ureteral obstruction model (UUO). Sham operated control rats were compared with UUO rats treated with vehicle (UUO-Veh), or low (5 mg/kg body weight (UUO-LD) or high (25 mg/kg) (UUO-HD) dose isotretinoin. Kidneys were evaluated using reverse transcriptase-polymerase chain reaction and immunohistology 7 days after UUO. Renal injury and fibrosis were quantified by immunostaining and expression measurements of the genes involved in renal fibrosis. In UUO-Veh kidneys the interstitial area was expanded 5-fold but only 3-fold in UUO-HD and 3.5-fold in UUO-LD rats. Interstitial cell counts were 3-fold higher in UUO-Veh rats but significantly less in UUO-HD or UUO-LD animals. Tubular and interstitial cell proliferation was significantly higher in UUO-Veh rats compared with sham operated control plus vehicle animals but less so in UUO-LD and UUO-HD rats. In UUO-Veh rats interstitial infiltration by monocytes/macrophages was higher compared with unobstructed controls. It was significantly less after isotretinoin treatment. In UUO-Veh rats mRNA for procollagen I, and transforming growth factor-beta1 and II receptor was significantly increased. It was significantly less after treatment with isotretinoin. Fibronectin and collagen I immunostaining was also decreased by isotretinoin. Since isotretinoin limits proliferation, inflammation and fibrosis after UUO, retinoids should be further investigated as potentially promising therapeutic agents for renal disease.

Systemic angiotensin II alters intrinsic heart rate through central mechanisms

Angiotensin II (ang II)-induced increases in intrinsic heart rate (IHR), and the resulting tachycardia, may contribute to development of renal hypertension. Whether circulating ang II affects the cardiac pacemaker through peripheral mechanisms or through actions in the central nervous system (CNS) has not been directly tested. These studies determined the role of a central site of ang II action, the tissue surrounding the anteroventral third ventricle (AV3V), in increased IHR induced by systemic ang II. Blood pressure and heart rate were measured in male rats with lesions of the AV3V region and in control-operated animals during i.v. infusion (3 h) of ang II, norepinephrine, or vehicle. IHR was evaluated at the end of the infusion period. Systemic ang II increased blood pressure equally in both experimental groups. However, heart rate was reduced only in animals with AV3V lesions. Furthermore, ang II increased IHR only in control-operated rats. Changes in blood pressure, heart rate, and IHR in response to norepinephrine infusion were similar between animals with AV3V lesions and control-operated rats. These data demonstrate that systemic ang II mediates IHR through actions in the CNS, specifically the AV3V region.

Renal cortical calcification in syngeneic intact rats and those receiving an infrarenal thoracic aortic graft: possible etiological roles of endothelin, nitrate and minerals, and different preventive effects of long-term oral treatment with magnesium, citrate and alkali-containing preparations.

Renal cortical nephrocalcinosis (C-NC) is a rare disorder of uncertain etiology. Using highly inbred (syngeneic) male Lewis rats, we describe the spontaneous occurrence of histologically detectable C-NC in sham operated control rats (Sham; n=12), its aggravation following grafting of the ascending thoracic aorta from a donor rat to the infrarenal aorta of a recipient (ATx; n=12), and differences in C-NC inhibition after 12 weeks of oral administration of magnesium (Mg), citrate and alkali. C-NC is characterized by Kossa-positive areas located in cells of the proximal tubule close to blood vessels and also, to a lesser extent, within glomeruli. After ATx there was vascular overproduction of endothelin (ET-1) but decreased production of nitrate; in renal cortical tissue there was an excess of calcium over Mg and phosphorus and oxalate over citrate. In plasma there was an increase in calcium and creatinine within the normal range. Calcification of tubular cells was eliminated by a preparation containing potassium, sodium and bases (from citrate degradation and bicarbonate) in addition to Mg. Less effective than the latter was Mg-potassium citrate and least effective, Mg citrate. The former treatment also normalized calcemia and urinary nitrate, but only incompletely suppressed ET-1 and had no significant effect on glomerular calcification or tissue and urinary oxalate. Urinary ET-1 excess appeared directly related to the cortical tissue calcium/Mg ratio, and urinary excretion of Mg, citrate and total protein appeared to be inversely related to the severity of C-NC. It was concluded that (1) the highly inbred rat is prone to precipitation of calcium phosphate in the renal cortex; (2) this type of C-NC occurs in close proximity to and within renal vascular tissue and is associated with an imbalance of vasoconstrictors and vasodilators of endothelial origin; (3) effective inhibition of C-NC can be achieved by an alkalinizing combination of Mg, potassium, sodium and citrate, underscoring its utility in the prophylaxis of pathological calcium phosphate deposition. The significance of these findings for the etiology and treatment of clinical disorders with renal and vascular calcification is uncertain and requires further investigation.

Place and Response Learning of Rats in a Morris Water Maze: Differential Effects of Fimbria Fornix and Medial Prefrontal Cortex Lesions

The question examined in this study is concerned with a possible functional dissociation between the hippocampal formation and the prefrontal cortex in spatial navigation. Wistar rats with hippocampal damage (inflicted by a bilateral lesion of the fimbria fornix), rats with damage to the medial prefrontal cortex, and control-operated rats were examined for their performance in either one of two different spatial tasks in a Morris water maze, a place learning task (requiring a locale system), or a response learning task (requiring a taxon system). Performance of the classical place learning (allocentric) task was found to be impaired in rats with lesions of the fimbria fornix, but not in rats with damage of the medial prefrontal cortex, while the opposite effect was found in the response learning (egocentric) task. These findings are indicative of a double functional dissociation of these two brain regions with respect to the two different forms of spatial navigation. When the place learning task was modified by relocating the platform, the impairment in animals with fimbria fornix lesions was even more pronounced than before, while the performance of animals with medial prefrontal cortex lesions was similar to that of their controls. When the task was again modified by changing the hidden platform for a clearly visible one (visual cue task), the animals with fimbria fornix lesions had, at least initially, shorter latencies than their controls. By contrast, in the animals with medial prefrontal cortex damage this change led to a slight increase in escape latency.

CONTRALATERAL COMPENSATORY KIDNEY GROWTH IN RATS WITH PARTIAL UNILATERAL URETERAL OBSTRUCTION MONITORED BY MAGNETIC RESONANCE IMAGING

Purpose We studied dynamic changes in total volume and renal vein blood flow in the kidneys contralateral to partial ureteral obstruction induced in newborn rats. Materials and Methods Using magnetic resonance imaging we investigated changes in total kidney volume and renal vein blood flow in 20 rats with mild and 18 with severe partial ureteral obstruction that was induced on the left side 2 days after birth. A total of 15 sham operated control rats were also studied. Total kidney volume and renal vein blood flow were monitored sequentially every 2 to 6 weeks for a total of 24 weeks. Renal parenchymal volume measured in vivo by magnetic resonance imaging was compared with that measured in vitro at week 24. Results Total volume and renal vein blood flow increased significantly in contralateral nonobstructed kidneys from week 14 and thereafter in rats with severe partial unilateral ureteral obstruction. At week 24 volume had increased by 22% and blood flow had increased by 25%. Volume and flow did not increase significantly in contralateral nonobstructed kidneys in rats with partial unilateral ureteral obstruction (p = 0.09). Before changes occurred in volume and blood flow in the contralateral nonobstructed kidneys, renal vein blood flow had decreased significantly from week 8 and thereafter in severely obstructed kidneys. In rats with mild partial unilateral ureteral obstruction renal vein blood flow decreased significantly in obstructed kidneys from week 18 and thereafter. Good correlation was noted between MRI in vivo and in vitro kidney volume measurements (r = 0.972, p <0.001). Conclusions A significant increase in total volume and renal vein blood flow in contralateral nonobstructed kidneys did not develop immediately after the onset of detectable functional deterioration in partially obstructed kidneys. Therefore, caution should be used when incorporating compensatory growth into surgical decision making.