Rats In Normal Saline Research Articles

Identification and characterization of N6-methyladenosine circular RNAs in the spinal cord of morphine-tolerant rats.

Morphine tolerance (MT) is a tricky problem, the mechanism of it is currently unknown. Circular RNAs (circRNAs) serve significant functions in the biological processes (BPs) of the central nervous system. N6-methyladenosine (m6A), as a key post-transcriptional modification of RNA, can regulate the metabolism and functions of circRNAs. Here we explore the patterns of m6A-methylation of circRNAs in the spinal cord of morphine-tolerant rats. In brief, we constructed a morphine-tolerant rat model, performed m6A epitranscriptomic microarray using RNA samples collected from the spinal cords of morphine-tolerant rats and normal saline rats, and implemented the bioinformatics analysis. In the spinal cord of morphine-tolerant rats, 120 circRNAs with different m6A modifications were identified, 54 of which were hypermethylated and 66 of which were hypomethylated. Functional analysis of these m6A circRNAs found some important pathways involved in the pathogenesis of MT, such as the calcium signaling pathway. In the m6A circRNA-miRNA networks, several critical miRNAs that participated in the occurrence and development of MT were discovered to bind to these m6A circRNAs, such as miR-873a-5p, miR-103-1-5p, miR-107-5p. M6A modification of circRNAs may be involved in the pathogenesis of MT. These findings may lead to new insights into the epigenetic etiology and pathology of MT.

LncRNA MEG3 activates CDH2 expression by recruitment of EP300 in valproic acid-induced autism spectrum disorder

LncRNAs partake in the biological processes contributing to development of autism spectrum disorder (ASD). The aim of the present study is to investigate the effects of lncRNA maternally expressed gene 3 (MEG3) on viability and apoptosis of hippocampal neurons from ASD rats. Rats with ASD were induced using valproic acid (VPA) with normal saline (NS) as control. We performed microarray analysis on hippocampal tissues of NS rats and ASD rats to screen the differentially expressed lncRNAs. MEG3 loss in rats alleviated the impairment of learning and memory abilities induced by VPA, and promoted neuronal viability and inhibited apoptosis. MEG3 could recruit the transcription factor E1A binding protein p300 (EP300) in the nucleus and promote the cadherin 2 (CDH2) expression. CDH2 depletion in rats ameliorated the impairment of learning and memory capacities in ASD rats. After upregulation of CDH2 in neurons with sh-MEG3, we found diminished viability and increased apoptosis in hippocampal neurons of ASD rats. Taken together, MEG3 supports activation of CDH2 via EP300, thus repressing the viability of hippocampal neurons. Therefore, MEG3 upregulation may be partially responsible for the pathogenesis of ASD.

Effects of human parathyroid hormone 1–34 on bone loss and lumbar intervertebral disc degeneration in ovariectomized rats

Lumbar intervertebral disc degeneration is a common cause of lower back pain that affects the physical and mental health of patients and increases social burden. Parathyroid hormone has been reported to be effective at inhibiting disc degeneration; however, these effects have not been fully established in vivo in ovariectomized (OVX) rats. Thus, in this study, we aimed to address this issue and examine the effects of parathyroid hormone treatment in OVX rats. Thirty female Sprague-Dawley rats, three months-old, were subjected to sham or ovariectomy surgery. Twelve weeks postsurgery, OVX rats were treated with either human parathyroid hormone [hPTH(1-34), 30μg/kg/day] or vehicle (normal saline (NS)) treatment. The L3-6 spinal segments were harvested after 12weeks treatment. Bone mineral density (BMD), micro-architectural parameters, and biomechanical assessment were measured at the lumbar vertebral bodies. Histology and immunohistochemistry were performed to analyze the characteristics of the lumbar intervertebral discs. OVX + PTH rats had significantly higher BMD, percentage bone volume density, trabecular thickness, and biomechanical strength compared with those in Sham and OVX + NS rats. Histology and immunostaining revealed that disc degeneration was not significantly different between the OVX + NS rats and the OVX + PTH rats, compared with the Sham group; the structure of nucleus pulposus was disordered, the expression of collagen I was increased, and collagen II and aggrecan were decreased. These findings confirmed that hPTH(1-34) treatment has substantial anabolic effects on bone mass and trabecular micro-architecture, while the excessively enhanced bone mass and strength were coupled with a non-significant effect on the disc degeneration in ovariectomized rats.

Cardiac μ-opioid receptor contributes to opioid-induced cardioprotection in chronic heart failure

BackgroundThe therapeutic potential of cardiac μ-opioid receptors in ischaemia-reperfusion (I/R) injury during opioid-modulating diseases, such as heart failure, is unknown. We aimed to explore the changes of cardiac μ-opioid receptor expression during heart failure, and its role in opioid-induced cardioprotection. MethodsRats received doxorubicin (DOX) or were subjected to coronary artery ligation to induce heart failure, or received normal saline (NS) as control. Hearts from NS or DOX rats were isolated and subjected to myocardial ischaemia and reperfusion in an in vitro perfusion system. The opioid [D-Ala,2N-MePhe,4 Gly-ol]-enkephalin (DAMGO), with a high μ-opioid receptor specificity, morphine, and remifentanil were administrated before I/R with or without opioid receptor antagonists, or an extracellular signal-regulated kinase (ERK) inhibitor. ResultsCardiac μ-opioid receptor mRNA concentrations were 3.2 times elevated in DOX-treated rats compared with NS rats, while cardiac μ-opioid receptor protein concentrations showed 6.1- and 3.5-fold increases in DOX-treated and post-infarcted rats, respectively. DAMGO reduced I/R-caused infarct size, expressed as the ratio of area at risk, from 0.50 (0.04) to 0.25 (0.03) in failing rat hearts, but had no effect on infarct size in control hearts. DAMGO promoted phosphorylation of ERK and glycogen synthase kinase (GSK)-3β only in failing hearts. DAMGO-mediated cardioprotection was blocked by an ERK inhibitor. The μ-opioid receptor antagonist D-Pen-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) prevented morphine- and remifentanil-induced cardioprotection and phosphorylation of ERK and GSK-3β in failing hearts. In contrast, δ- and κ-opioid receptor selective antagonists were less potent than CTOP in the failing hearts. ConclusionsCardiac μ-opioid receptors were substantially up-regulated during heart failure, which increased DAMGO-induced cardioprotection against I/R injury.

Blockage of High-Affinity Choline Transporter Increases Visceral Hypersensitivity in Rats with Chronic Stress.

Background Visceral hypersensitivity is a common feature of irritable bowel syndrome. Cholinergic system involves in the development of visceral hypersensitivity, and high-affinity choline transporter (CHT1) is of crucial importance in choline uptake system. However, involvement of CHT1 in visceral hypersensitivity remains unknown. The research aimed to study the CHT1 expression in dorsal root ganglions (DRGs) and the role of CHT1 in visceral hypersensitivity. Methods Repetitive water avoidance stress (WAS) was used to induce visceral hypersensitivity in rats. Colorectal distension (CRD) was determined, and the abdominal withdrawal reflex (AWR) and threshold intensity data were recorded to measure the visceral sensitivity. After intraperitoneal injection of hemicholinium-3 (HC-3), the specific inhibitor of CHT1, CRD data were also recorded. The CHT1 expression of DRGs was investigated by Western blotting, immunohistochemistry, and quantitative RT-PCR. Acetylcholine levels in the DRGs were detected by the assay kit. Results Repetitive WAS increased the AWR score of CRD at high distension pressure and decreased the mean threshold of rats. The CHT1 expression and acetylcholine concentration of DRG were significantly increased in WAS rats. After the administration of HC-3, the AWR score in WAS group was significantly increased at higher distension pressure while the threshold intensity was significantly reduced compared to the normal saline group. Acetylcholine concentration was significantly lower than the normal saline rats. Conclusion Our research firstly reports that CHT1 is overexpressed in noninflammatory visceral hypersensitivity, and blockage of CHT1 can enhance the visceral hypersensitivity. CHT1 may play an inhibitory role in visceral hypersensitivity.

Changes of platelet rheological behavior and the interventional effects of ulinastatin in rats with high-voltage electrical burns

Changes of platelet rheological behavior and the interventional effects of ulinastatin in rats with high-voltage electrical burns

Effects of resveratrol on motor function and anterior horn neuron of spinal cord following acute sciatic nerve compression injury in rats

Objective To investigate the effects of resveratrol (Res) on motor function and the anterior horn neuron of lumbar spinal cord after acute sciatic nerve compression injury in rats. Methods The rat model with acute sciatic nerve compression injury was established in 32 Sprague Dawley (SD) rats, which were randomly divided into four groups: Res group, Dimethyl Sulfoxide (DMSO) group, Normal Saline (NS) group and sham-operation group. Res, DMSO and saline were successively injected by intraperitoneal for 10 days after established crush acute sciatic nerve compression injury model, while sham-operation group was sutured only after exposure to the sciatic nerve. The weight, the change of toe extension angle, and the sciatic functional index (SFI) of rats were observed at the 1st day before operation and the 1st, 3rd, 7th, and 10th days after surgery. The expressions of neuron-specific nuclear protein (NeuN) and microtubule-associate protein 2 (MAP2) were detected by immunofluorescent staining of L4-L6 spinal cord anterior horn on the 10th day after surgery. Results No significant changes were found in the weight of rats among four groups. Compared to the sham, the motor function of the injured limb in Res, DMSO, and NS rats was impaired, and the anterior horn neurons were seriously damaged. But the differences of the change of toe extension and the sciatic functional index of rats were significantly higher in Res group than that of the DMSO group and NS group (P<0.01) at the 3rd, 7th, and 10th days after surgery. The expressions of NeuN and MAP2 in the anterior horn of rat lumbar spinal cord were up-regulated in Res group relative to DMSO and NS, and the number of neurons in the lumbar spinal cord was significantly relieved at the 10th days. Conclusions Res was significant to rat model of acute sciatic nerve injury, which could increase the number of neurons in the anterior horn of the spinal cord and help the recovery of motor function. Key words: Veratrum alkaloids/PD; Sciatic nerve/IN; Motor activity/DE; Anterior horn cells/DE

Effects of lappaconitine on pain and inflammatory response of severely burned rats and the mechanism

Effects of lappaconitine on pain and inflammatory response of severely burned rats and the mechanism

Hyperbaric Oxygen Pretreatment Improves Cognition and Reduces Hippocampal Damage Via p38 Mitogen-Activated Protein Kinase in a Rat Model.

PurposeTo investigate the effects of hyperbaric oxygen (HBO) pretreatment on cognitive decline and neuronal damage in an Alzheimer’s disease (AD) rat model.Materials and MethodsRats were divided into three groups: normal saline (NS), AD, and HBO+AD. In the AD group, amyloid β peptide (Aβ)1-40 was injected into the hippocampal CA1 region of the brain. NS rats received NS injection. In the HBO+AD group, rats received 5 days of daily HBO therapy following Aβ1-40 injection. Learning and memory capabilities were examined using the Morris water maze task. Neuronal damage and astrocyte activation were evaluated by hematoxylin-eosin staining and immunohistochemistry, respectively. Dendritic spine density was determined by Golgi-Cox staining. Tumor necrosis factor-α, interleukin-1β, and interleukin-10 production was assessed by enzyme-linked immunosorbent assay. Neuron apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Protein expression was examined by western blotting.ResultsLearning and memory dysfunction was ameliorated in the HBO+AD group, as shown by significantly lower swimming distances and escape latency, compared to the AD group. Lower rates of neuronal damage, astrocyte activation, dendritic spine loss, and hippocampal neuron apoptosis were seen in the HBO+AD than in the AD group. A lower rate of hippocampal p38 mitogen-activated protein kinase (MAPK) phosphorylation was observed in the HBO+AD than in the AD group.ConclusionHBO pretreatment improves cognition and reduces hippocampal damage via p38 MAPK in AD rats.

Effect of Nourishing "Yin" Removing "Fire" Chinese Herbal Mixture on Hypothalamic Mammalian Target of Rapamycin Expression during Onset of Puberty in Female Rats.

Aim. The present study aims to investigate the effects of nourishing “Yin” removing “Fire” (NYRF) Chinese herbal mixture on puberty onset and hypothalamic mTOR expression in female rats. Materials and Methods. Forty female 20-day-old Sprague-Dawley rats were randomly divided into Chinese herbal mixture (CHM) and normal saline (NS) groups. Rats in CHM and NS were treated with NYRF mixture and normal saline, respectively, from d22. Rats in each group were sacrificed on d28, d31, and d34. Serum luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E2) levels were analyzed by ELISA. Hypothalamic mTOR mRNA expression levels were determined by RT-PCR and hypothalamic p-mTOR protein levels were assayed by western blot. Results. The vaginal opening time in CHM group was significantly delayed (P < 0.05). On d31, in comparison with NS group, the coefficients of uteri and ovaries, levels of serum LH and E2, and the expression levels of hypothalamic mTOR mRNA and p-mTOR protein were significantly lower in CHM group (P < 0.05). Conclusion. The mechanism by which the nourishing “Yin” removing “Fire” Chinese herbal mixture delays puberty onset may be associated with the inhibition of the hypothalamic mTOR signaling.

Microinjection of HSV-1 Amplicon Vector-Mediated Human Proenkephalin into the Periaqueductal Grey Attenuates Neuropathic Pain in Rats

ABSTRACTWe investigated the antinociceptive effect of microinjection of HSV-1 amplicon vector-mediated human proenkephalin (hPPE) into the ventral periaqueductal grey (PAG) on neuropathic pain in rats. Male Sprague-Dawley rats with chronic constriction injury (CCI)-induced neuropathic pain were microinjected into the ventral PAG with normal saline (NS), pHSVIRES-lacZ (SHZ), or HSV-1 amplicon vector pHSVIRES-hPPE-lacZ (SHPZ), respectively. Pain thresholds in the SHPZ-treated rats were significantly higher at day 3, then reached peak at day 14 and lasted until day 35 after PAG administration, and these effects were reversed by naloxone. In contrast, NS or SHZ-treated rats did not significantly affect pain thresholds. These results demonstrated that microinjection of HSV-1 amplicon vector-mediated hPPE into the ventral PAG attenuates neuropathic pain in rats.

Pirfenidone diminishes SiO2 induced lung fibrosis in rats

to investigate whether pirfenidone (PFD) presents the antifibrotic effect in silicosis of rats. SD rats were randomly divided into five groups: the non-treat group, the normal saline group, the normal saline + PFD group, the SiO2 group, the SiO2 + PFD group. Rats except in the non-treat group were intratracheally instilled with SiO2 (25 mg/ml) or normal saline. The rats in normal saline + PFD group and the SiO2 + PFD group were given PFD (50 mg/kg) orally the next day after instillation and throughout the study. Rats were respectively sacrificed 7, 21, 42 days after instillation. The pathology changes were evaluated by Haematoxylin-eosin (HE), Van Gieson and Foot staining, and the hydroxyproline (HYP) content of pulmonary tissue was determined. compared with the SiO2 group, PFD could relieve the fibrotic changes in the lungs of rats. The fibrotic degree in silicotic lesions of lungs was lower in the SiO2 + PFD group than that of SiO2 group. The HYP content in the lungs of the SiO2 + PFD group [(0.75 ± 0.12) mg/g] was significantly lower than that of the SiO2 group [(1.19 ± 0.17) mg/g] at 42 days after instillation (P < 0.05). these data support that PFD has an antifibrotic effect against SiO2 induced lung fibrosis in rats, Which appears to be changing collagen accumulation and inhibiting pulmonary fibrosis.

Effects of hepatotrophic factors on the liver after portacaval shunt in rats with portal hypertension

Portacaval shunt (PCS) prevent hepatotrophic factors from flowing into the liver, but they enter directly the systemic circulation and worsen liver injury. This study was designed to investigate the effects of hepatotrophic factors through the portal vein on the liver in rats with portal hypertension after portacaval shunt. Intrahepatic portal hypertension (IHPH) was induced by intragastric administration of carbon tetrachloride, and end-to-side PCS was performed. Eight normal rats served as controls, and eight rats with IHPH served as IHPH model (IHPH group). Another 32 rats with IHPH-PCS were randomly subdivided into 4 groups: normal saline (NS) given to 8 rats, hepatocyte growth factor (HGF) 8, insulin (INS) 8, hepatocyte growth factor and insulin (HGF + INS) 8. Hepatotrophic factors were infused into the portal vein through an intravenous catheter. Portal venous pressure (PVP) was measured. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested biochemically and those of hyaluronic acid (HA) and laminin (LN) were measured by radioimmunoassay. Hepatic fibrosis was assessed histologically and the expression of collagens type I and III were detected immunohistochemically. Ultrastructural change of hepatocytes and the number of mitochondria were observed under an electron microscope. The data were compared between groups and subgroups by Student-Newman-Keuls procedure with SPSS10.0. PVP was significantly higher in the IHPH rats than in the control rats (P < 0.05). The levels of serum ALT, AST, HA, and LN, hepatic fibrosis score, the amount of collagen deposition, collagens type I and III increased more significantly in the IHPH group than in the control rats (P < 0.05). The number of mitochondria decreased more significantly in the IHPH rats than in the control rats (P < 0.05). The levels of serum ALT, AST, HA and LN as well as hepatic fibrosis score, the amount of collagen deposition, and the amount of collagens type I and III in the HGF and HGF + INS rats were significantly lower than those in the NS rats (P < 0.05). The damage to hepatocyte ultrastructure was markedly alleviated and the number of mitochondria was increased more significantly in the HGF and HGF + INS rats than in the NS rats under an electron microscope. Perfusion of exogenous hepatotrophic factors through the portal vein can alleviate liver injury, minimize the damage to the ultrastructure of hepatocyte, protect liver function, and lessen hepatic fibrosis in rats with portal hypertension after PCS.

Effects of octreotide on epidermal growth factor receptor, tissue plasminogen activator, and plasminogen activator inhibitor during intraperitoneal adhesion formation.

Intraperitoneal adhesions remain a problem after abdominal surgery. Octreotide has been proved to be able to reduce the number, strength, and extent of fibrous bands at and away from the anastomotic site in an animal model of rats with intestinal resection and reanastomosis. The aim of the present study was to investigate whether epidermal growth factor receptor (EGF-R), tissue plasminogen activator (tPA), and plasminogen activator inhibitor (PAI) are involved in this process. Laparotomy with intestinal resection and reanastomosis was performed on 60 male Wistar rats. All rats were randomly assigned to five groups: receiving no medication (control; C), normal saline (NS), octreotide solution peritoneal irrigation (Oc), octreotide intramuscular injection (IM), and Oc plus octreotide intramuscular injection (Oc + IM). The concentrations of serum EGF-R, plasma tPA, PAI-1, and PAI-2, and the strength of wound healing were measured. The serum EGF-R concentration showed no significant change from the preoperative level in the C and NS groups 7 and 14 days after the abdominal surgery. However, it decreased significantly on postoperative days 7 and 14 in groups Oc, IM, and Oc + IM ( P < 0.05). The plasma tPA concentrations were significantly higher than the preoperative level in all groups of rats on postoperative day 7. The levels were higher in groups Oc, IM, and Oc + IM than in group C or group NS at that time ( P < 0.05). On postoperative day 14, the plasma tPA concentrations had returned to the preoperative level in group C and group NS. However, the concentrations in groups Oc, IM, and Oc + IM still remained at a significantly higher level than the concentrations in group C and group NS. The plasma PAI-1 and PAI-2 concentrations showed no significant difference from the preoperative level in group C and group NS on days 7 and 14 after the abdominal surgery. However, the concentrations in groups Oc, IM, and Oc + IM on postoperative days 7 and 14 were markedly lower than those in groups C and NS ( P < 0.05). The wound strength was significantly greater on day 14 than on day 7 in all groups. In the rats with octreotide irrigation, the EGF-R level was decreased, the plasma tPA concentration was higher, and the plasma PAI-1 and PAI-2 concentrations were lower when compared with values in group C and group NS rats on days 7 and 14 after surgery. The data suggest that EGF-R, tPA, PAI-1, and PAI-2 are all involved in the mechanism of octreotide's action in reducing adhesion formation.

Long-term, low-dose, cadmium-induced nephropathy with renal osteopathy in ovariectomized rats.

To establish an animal model of chronic cadmium nephropathy and osteopathy, we intraperitoneally administered 0.228 mg CdCl2 (Cd) or normal saline (NS) to 52 female Sprague-Dawley (S.D.) rats 3 times a week for 16 months following ovariectomy (OV) or sham surgery (Sham), dividing the animals into three experimental groups (OV-Cd, Sham-Cd and OV-NS). Two groups of male S.D. rats were also administered Cd or NS (22 animals; Male-Cd and Male-NS). Cd-administered rats gained significantly less body weight than NS rats after 16 months of experiments with no signs of emaciation. Serum creatinine levels and Cd contents in the kidney had significantly increased in the Cd-administered rats. OV-Cd rats showed significant decreases in PTH levels and increases in calcium contents in the kidney and other organs. Kidneys of Cd-administered rats showed atrophy, dilatation, and interstitial fibrosis of tubules. Sclerosis and collapse of the glomeruli were observed in the Cd groups with no proliferation in mesangial cells or matrix. The Haversian canal system of the Cd-administered rats disappeared and was replaced by a large quantity of degenerated, necrotic, and restorative tissues. Bone histomorphometric parameters showed that osteoid volume and osteoid surface had significantly increased in the Male-Cd group. In contrast, decreases in bone mass and increases in fibrous tissue were found to be more prominent in the OV-Cd group. Our results have demonstrated for the first time that long-term, low-dose CdCl2 administration to ovariectomized S.D. rats is capable of inducing irreversible nephropathy with osteopathy exhibiting pathological and bone histomorphometric characteristics that are very similar to those of Itai-Itai disease.

Mechanical characteristics of the globally ischaemic heart

The aim was to study the effects of global ischaemia on the mechanical properties of the myocardium. Myocardial ischaemia was achieved by incubating the hearts of 160 rats in normal saline at 37 degrees C for periods of up to 24 h. To obtain different degrees of contracture, excess pressure (up to 150 mm Hg) was created in the left ventricles of subgroups of hearts. After incubation the hearts underwent mechanical loading. Ischaemic contracture of cardiomyocytes led to increased rigidity and strength of the myocardium. A pressure of 50 mm Hg or higher blocked the increase in strength and rigidity of the ischaemic myocardium. It appears likely that in a functioning heart cardiomyocyte contracture in an ischaemic zone can only develop during the diastolic phase. A decrease in diastolic duration and/or an increase in diastolic pressure in the left ventricle may prevent increases in strength and rigidity of the ventricular wall after an infarct and promote the development of aneurysm and possible cardiac rupture.

Postischemic hemodynamics and recovery of renal adenosine triphosphate.

Renal vasoconstriction is an important pathophysiological component of an ischemic acute renal injury. The postischemic infusion of ATP-MgCl2 enhances recovery of glomerular and tubular function, accelerates regeneration of sublethally injured tubular cells, and augments resynthesis of cellular nucleotides. Since both ATP and MgCl2 are vasoactive compounds, postischemic enhancement of renal blood flow (RBF) by a pharmacological agent, dopamine, was examined to study the possible contribution of vasodilation. At 2 h, the infusion of dopamine resulted in RBF (1.70 +/- 0.09 ml X min-1 X 100 g body wt-1 X kidney-1) and inulin clearance (CIn, 400 +/- 44 microliter X min-1 X 100 g body wt-1) similar to rats treated with ATP-MgCl2 (1.73 +/- 0.27 RBF, 404 +/- 38 CIn) and significantly (P less than 0.01) greater than saline-treated rats (0.80 +/- 0.04 RBF, 78 +/- 19 CIn; P less than 0.01). However, by 24 h CIn in dopamine animals had not continued to improve (460 +/- 25 microliter X min-1 X 100 g body wt-1) and was similar to normal saline rats (388 +/- 40). In contrast, CIn in ATP-MgCl2 animals showed sustained recovery (676 +/- 28 microliter X min-1 X 100 g body wt-1, P less than 0.01). These differences resulted from improved integrity of tubular epithelium as reflected by decreased cell swelling and necrosis. Moreover, the recovery of renal ATP levels, as assessed by 31P nuclear magnetic resonance, in animals given saline (63 +/- 3%) or dopamine (66 +/- 5%) was slow and incomplete by 120 min after ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

HEMODYNAMIC EFFECT OF POST-ISCHEMIC ATP-MGCL2

The postischemic infusion of ATP-MgCl2 is known to enhance recovery from acute renal failure. Since both ATP and MgCl2 are vasoactive compounds and increase renal blood flow (RBF), the hemodynamic effects of this complex were determined by treating animals with either dopamine (15 μg/kg), ATP-MgCl2 (25 μmoles) or normal saline (NS) after 45 min of renal ischemia. Inulin clearance (Cin) and renal blood flow (electromagnetic flow probe) were determined at 2 hrs and Cin and recovery of microinjected inulin (InR%) were evaluated 24 hrs after the injury.At 2 hrs the infusion of dopamine resulted in a level of RBF (1.70±0.09 ml/min/100gBW/kidney) and Cin (400±44 μl/min/100gBW) that was similar to that in the ATP-MgCl2 rats (1.73±0.27 RBF, 404±38 Cin and significantly (P<0.01) greater than NS rats (0.80±0.04 RBF, 78±19 Cin; P<0.01). However, by 24 hrs the Cin in dopamine animals had not continued to improve (460±25) and was similar to that in NS animals (388±40). In contrast, Cin in ATP-MgCl2 animals showed sustained and accelerated recovery (676±28; P<0.01). These differences resulted from improved integrity of the tubular epithelium as reflected by diminished backleak: InR 92±3% ATP-MgCl2; 45±5% dopamine; P<0.01).This study demonstrates that the initial hemodynamic effect of ATP-MgCl2 produces some improvement in Cin but the sustained salutary effect of this compound is related to the repair of sublethally injured tubular cells and restoration of cellular metabolism, which we have previously documented.