Treatment Of Normal Rats Research Articles

Spine Enlargement of Pyramidal Tract-Type Neurons in the Motor Cortex of a Rat Model of Levodopa-Induced Dyskinesia.

Growing evidence suggests that abnormal synaptic plasticity of cortical neurons underlies levodopa-induced dyskinesia (LID) in Parkinson's disease (PD). Spine morphology reflects synaptic plasticity resulting from glutamatergic transmission. We previously reported that enlargement of the dendritic spines of intratelencephalic-type (IT) neurons in the primary motor cortex (M1) is linked to the development of LID. However, the relevance of another M1 neuron type, pyramidal-tract (PT) neurons, to LID remains unknown. We examined the morphological changes of the dendritic spines of M1 PT neurons in a rat model of LID. We quantified the density and size of these spines in 6-hydroxydopamine-lesioned rats (a model of PD), 6-hydroxydopamine-lesioned rats chronically treated with levodopa (a model of LID), and control rats chronically treated with levodopa. Dopaminergic denervation alone had no effect on spine density and head area. However, the LID model showed significant increases in the density and spine head area and the development of dyskinetic movements. In contrast, levodopa treatment of normal rats increased spine density alone. Although, chronic levodopa treatment increases PT neuron spine density, with or without dopaminergic denervation, enlargement of PT neuron spines appears to be a specific feature of LID. This finding suggests that PT neurons become hyperexcited in the LID model, in parallel with the enlargement of spines. Thus, spine enlargement, and the resultant hyperexcitability of PT pyramidal neurons, in the M1 cortex might contribute to abnormal cortical neuronal plasticity in LID.

Antidiabetic and antioxidant effects of Annona muricata (Annonaceae), aqueous extract on streptozotocin-induced diabetic rats

Ethnopharmacological relevanceThe leaves of Annona muricata are used in Cameroon to manage diabetes and its complications. The aim of this study was to evaluate the antidiabetic, antioxidant activities and the potential toxicity of aqueous extract of Annona muricata in streptozotocin-induced diabetic rats. Material and methodsOral administration of Annona muricata aqueous extract (100mg/kg or 200mg/kg) was studied in normal and streptozotocin-induced diabetic rats. In long term treatment, 2 weeks after streptozotocin-induced diabetic rats, animals received plant extract during 28 consecutive days. For a protective effect, extract was administered 3 days prior to streptozotocin exposure and animals were observed 2 weeks without treatment. ResultsThe plant extract was not effective in normal rats. In diabetic rats, single administration of the extract significantly reduced blood glucose levels by 75% and 58.22% respectively at the dose of 100mg/kg and 200mg/kg as compared to the initial value. Treatment of normal rats 3 days prior to diabetes induction showed that, Annona muricata extract has no effect within 72h following STZ injection. However, after 14 days post-treatment, the extract at the dose of 100mg/kg significantly reduced blood glucose levels as compared with initial value and diabetic control rats. Immunohistochemical staining of pancreatic β-cells of diabetic rats treated with the dose of 100mg/kg expressed strong staining for β-cell compared to diabetic control. In a long-term study daily administration of Annona muricata aqueous extract for 28 days to diabetic rats, reduced blood glucose levels, serum creatinine, MDA, AST, ALT activity, and nitrite levels LDL-cholesterol. Total cholesterol, triglycerides, SOD, and CAT activity contents were restored. ConclusionThese different results show that the antidiabetic activity of Annona muricata aqueous extract can be explained by its hypolipidaemic effect, its antioxidant and protective action on pancreatic β-cells, which in turn improve glucose metabolism.

Regulation by Bisoprolol for Cardiac MicroRNA Expression in a Rat Volume-Overload Heart Failure Model

Emerging evidence suggests the involvement of altered microRNA (miRNA) regulation in heart failure pathogenesis. We established a rat volume-overload heart failure model, and examined miRNA expression in normal rats and in the heart failure model, both with and without treatment with bisoprolol. Using miRNA microarrays, we identified 46 differentially expressed miRNAs in the rat heart failure model compared with normal rats. We also identified 18 differentially expressed miRNAs following treatment of normal rats with bisoprolol. Treatment with bisoprolol reversed, to varying degrees, the expression of 10 of the 46 miRNAs whose expression was differentially expressed in the heart failure model. Bioinformatic category analysis of the predicted target genes of these 10 miRNAs suggested that several encode ion-binding proteins. Our results showed that bisoprolol intervention can significantly improve cardiac function and decrease myocardial reconstruction in chronic heart failure. These data suggest that the expression of many miRNAs changes during heart failure, and that bisoprolol may exert its cardioprotective effects in part by reversing the differential expression of some of these genes.

Mechanisms of right heart failure-A work in progress and a plea for failure prevention.

Mechanisms of right heart failure-A work in progress and a plea for failure prevention.

Acute nicotine treatment prevents rem sleep deprivation‐induced learning and memory impairment in rat

Rapid eye movement (REM) sleep deprivation (SD) is implicated in impairment of spatial learning and memory and hippocampal long-term potentiation (LTP). An increase in nicotine consumption among habitual smokers and initiation of tobacco use by nonsmokers was observed during SD. Although nicotine treatment was reported to attenuate the impairment of learning and memory and LTP associated with several mental disorders, the effect of nicotine on SD-induced learning and memory impairment has not been studied. Modified multiple platform paradigm was used to induce SD for 24 or 48 h during which rats were injected with saline or nicotine (1 mg kg(-1) s.c.) twice a day. In the radial arm water maze (RAWM) task, 24- or 48-h SD significantly impaired learning and short-term memory. In addition, extracellular recordings from CA1 and dentate gyrus (DG) regions of the hippocampus in urethane anesthetized rats showed a significant impairment of LTP after 24- and 48-h SD. Treatment of normal rats with nicotine for 24 or 48 h did not enhance spatial learning and memory or affect magnitude of LTP in the CA1 and DG regions. However, concurrent, acute treatment of rats with nicotine significantly attenuated SD-induced impairment of learning and STM and prevented SD-induced impairment of LTP in the CA1 and DG regions. These results show that acute nicotine treatment prevented the deleterious effect of sleep loss on cognitive abilities and synaptic plasticity.

The effect of metyrapone on granuloma induced by carrageenan-impregnated sponges in normal and essential fatty acid deficient rats.

Treatment of normal rats with metyrapone (20 mg kg-1 day-1, s.c.) for 5 days, starting on the day before implantation, inhibited the production of granuloma, induced by carrageenan-impregnated sponges, determined 8 days after implantation. Exudate volume and prostaglandin (PG) production were unaffected. In essential fatty acid deficient (EFAD) rats, metyrapone did not alter the already existing adrenal hyperplasia due to EFAD and did not affect either granuloma formation or exudate production. The results are discussed in relation to earlier work using adrenalectomy and with regard to the effect of EFA deficiency on adrenal corticosteroid production. It is suggested that metyrapone is a more useful tool than adrenalectomy in studying the role of endogenous corticosteroids.

Effect of different thyroid state on ornithine decarboxylase activity and receptors of T3 in rat liver.

The effects of thyreoidectomy, of the administration of 3,5,3'-triiodothyronine (T3), of thyroxine (T4) together with the inhibitor of iodothyronine 5'-deiodinase activity 6-propyl-2-thiouracil (PTU) and of PTU alone on rat liver ornithine decarboxylase (ODC) activity was studied. 28 days after thyroidectomy there was a decrease in ODC activity, whereas T3 treatment of normal rats increased enzyme activity. PTU decreased ODC activity in intact rats and inhibited ODC activity in animals treated with T4. Neither thyroidectomy T3, T4 given in vivo nor the polyamines spermine and spermidine added in vitro influenced the binding of 125I-T3 to its receptor in liver nuclei. Only addition of PTU increased Ka significantly (P less than 0.01). It is concluded that ODC activity in the liver is directly correlated with the thyroid state but not to parameters of thyroid hormone receptor in liver nuclei.

Antihyperglycaemic and Antioxidant Effect of Rutin, a Polyphenolic Flavonoid, in Streptozotocin‐Induced Diabetic Wistar Rats

Flavonoids are non-nutritive dietary components that are widely distributed in plants. The present study investigated the antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid in normal and streptozotocin-induced diabetic Wistar rats. Diabetes as induced in rats by an intraperitoneal injection of streptozotocin. Rutin was orally administered to normal and diabetic rats for a period of 45 days. Fasting plasma glucose, glycosylated haemoglobin, thiobarbituric acid reactive substances and lipid hydroperoxides were significantly (P<0.05) increased, whereas insulin, C-peptide, total haemoglobin, protein levels, non-enzymic antioxidants (glutathione, vitamin C, vitamin E and ceruloplasmin) were decreased significantly (P<0.05) in diabetic rats. Oral administration of rutin to diabetic rats significantly (P<0.05) decreased fasting plasma glucose, glycosylated haemoglobin and increased insulin, C-peptide, haemoglobin and protein levels. Administration of rutin also decreased thiobarbituric acid reactive substances and lipid hydroperoxides and increased the non-enzymic antioxidants significantly (P<0.05). Treatment of normal rats with rutin did not significantly (P<0.05) alter any of the parameters studied. These results show that rutin exhibits antihyperglycaemic and antioxidant activity in streptozotocin-induced diabetic rats.

Isolation and identification of 1α‐hydroxy‐3‐epi‐vitamin D3, a potent suppressor of parathyroid hormone secretion

Since our original demonstration of the metabolism of 1alpha,25(OH)2D3 into 1alpha,25(OH)2-3-epi-D3 in human keratinocytes, there have been several reports indicating that epimerization of the 3 hydroxyl group of vitamin D compounds is a common metabolic process. Recent studies reported the metabolism of 25OHD3 and 24(R),25(OH)2D3 into their respective C-3 epimers, indicating that the presence of 1alpha hydroxyl group is not necessary for the 3-epimerization of vitamin D compounds. To determine whether the presence of a 25 hydroxyl group is required for 3-epimerization of vitamin D compounds, we investigated the metabolism of 1alphaOHD3, a non-25 hydroxylated vitamin D compound, in rat osteosarcoma cells (ROS 17/2.8). We noted metabolism of 1alphaOHD3 into a less polar metabolite which was unequivocally identified as 1alphaOH-3-epi-D3 using the techniques of HPLC, GC/MS, and 1H-NMR analysis. We also identified 1alphaOH-3-epi-D3 as a circulating metabolite in rats treated with pharmacological concentrations of 1alphaOHD3. Thus, these results indicated that the presence of a 25 hydroxyl group is not required for 3-epimerization of vitamin D compounds. Furthermore, the results from the same studies also provided evidence to indicate that 1alphaOH-3-epi-D3, like 1alphaOHD3, is hydroxylated at C-25. We then evaluated the biological activities of 1alphaOH-3-epi-D3. Treatment of normal rats every other day for 7 days with 2.5 nmol/kg of 1alphaOH-3-epi-D3 did not raise serum calcium, while the same dose of 1alphaOHD3 increased serum calcium by 3.39 +/- 0.52 mg/dl. Interestingly, in the same rats which received 1alphaOH-3-epi-D3 we also noted a reduction in circulating PTH levels by 65 +/- 7%. This ability of 1alphaOH-3-epi-D3 to suppress PTH levels in normal rats without altering serum calcium was further tested in rats with reduced renal function. The results indicated that the ED50 of 1alphaOH-3-epi-D3 for suppression of PTH was only slightly higher than that of 1alpha,25(OH)2D3, but that the threshold dose of the development of hypercalcemia (total serum Ca > 10.5 mg/dl) was nearly 80 times higher. These findings indicate that 1alphaOH-3-epi-D3 is a highly selective vitamin D analog with tremendous potential for treatment of secondary hyperparathyroidism in chronic renal failure patients.

Regulation by carbohydrate and clofibric acid of palmitoyl-CoA chain elongation in the liver of rats.

Regulation of palmitoyl-CoA chain elongation (PCE) and its contribution to oleic acid formation were investigated in rat liver in comparison with stearoyl-CoA desaturase (SCD). Hepatic PCE activity was induced by the administration of 20% wt/vol glucose or fructose in the drinking water of normal rats. In streptozotocin-induced diabetic rats, the activities of both PCE and SCD were suppressed, and fructose, but not glucose, feeding caused an increase in the activities of both enzymes. Treatment of normal rats with clofibric acid in combination with carbohydrate further increased PCE, but not SCD, activity. FA analysis of hepatic lipids revealed that the proportion of oleic acid (18:1 n-9) increased upon administration of carbohydrate or clofibric acid. The treatment of rats with clofibric acid in combination with carbohydrate greatly increased the proportion of 18:1 n-9. A significant correlation was observed between PCE activity and the hepatic proportion of 18:1 n-9 (r2 = 0.874, P < 0.01), whereas the relationship between SCD activity and the proportion of 18:1 n-9 was not significant (r2 = 0.552, P > 0.05). Taken together, these results suggest that carbohydrate induces PCE as well as SCD activity to increase the hepatic 18:1 content in rat liver, and the increased PCE activity seems to be responsible for the further increase in 18:1 n-9 when carbohydrate is administered in combination with clofibric acid.

Axial heterogeneity in basolateral AQP2 localization in rat kidney: effect of vasopressin.

The purpose of the present study was to examine whether there is axial heterogeneity in the basolateral plasma membrane (BLM) localization of AQP2 and whether altered vasopressin action or medullary tonicity affects the BLM localization of AQP2. Immunocytochemistry and immunoelectron microscopy revealed AQP2 labeling of the BLM in connecting tubule (CNT) cells and inner medullary collecting duct (IMCD) principal cells in normal rats and vasopressin-deficient Brattleboro rats. In contrast there was little basolateral AQP2 labeling in cortical (CCD) and outer medullary collecting duct principal cells. Short-term desamino-Cys(1), (D)-Arg(8) vasopressin (dDAVP) treatment (2 h) of Brattleboro rats caused no increase in AQP2 labeling of the BLM. In contrast, long-term dDAVP treatment (6 days) of Brattleboro rats caused an increased BLM labeling in CNT, CCD, and IMCD. Treatment of normal rats with V(2)-receptor antagonist for 60 min caused retrieval of AQP2 from the apical plasma membrane. Moreover, AQP2 labeling of the BLM was unchanged in CNT and IMCD but increased in CCD. In conclusion, there is an axial heterogeneity in the subcellular localization of AQP2 with prominent AQP2 labeling of the BLM in CNT and IMCD. There was no increase in AQP2 labeling of the BLM in response to short-term dDAVP. Moreover, acute V(2)-receptor antagonist treatment did not cause retrieval of AQP2 from the BLM. In contrast, long-term dDAVP treatment caused a major increase in AQP2 expression in the BLM in CCD.

Effects of interleukin-15 (IL-15) on adipose tissue mass in rodent obesity models: evidence for direct IL-15 action on adipose tissue

Interleukin-15 (IL-15) is a proinflammatory cytokine with multifunctional effects outside the immune system. Previous studies have indicated that treatment of normal rats with IL-15 reduces white adipose tissue (WAT) mass, but it was unclear if these effects were direct or indirect. In the present study, the effects of IL-15 on WAT mass and lipid metabolism were studied in two genetic models of obesity: the leptin receptor-negative fa/fa Zucker rat and the leptin-deficient ob/ob mouse. Lean Zucker rats, lean (+/+), and obese mice ( ob/ob) responded to IL-15 with reductions in WAT mass and lipoprotein lipase activity (LPL), with no decreases in food intake. In contrast, fa/fa Zucker rats did not respond to IL-15 administration by any of the above measures of fat mass or lipid metabolism. In addition, ribonuclease protection assays (RPAs) were used to demonstrate that all three subunits (γc, β and α) of the IL-15 receptor complex are expressed by rat and mouse WAT, suggesting that the effects of IL-15 on adipose tissue metabolism could be direct. Additionally, the fa/fa rats expressed 84% lower levels of the γc signaling receptor subunit than lean Zucker rats, suggesting this decrease may play a role in the lack of adipose tissue response to IL-15 in the fa/fa genotype and lending further support for a direct action of IL-15 on adipose tissue.

Effects of aminoguanidine and desferrioxamine on some vascular and biochemical changes associated with streptozotocin-induced hyperglycaemia in rats

The effects of aminoguanidine (AG; 100 mgkg−1) and desferrioxamine (DFO; 50 mgkg−1) on some vascular and biochemical changes associated with streptozotocin (STZ; 65 mgkg−1; i.p.)-induced hyperglycaemia were investigated in rats. Both AG and DFO were administered i.p., once daily, for 14 consecutive days to normal and hyperglycaemic animals. The responsiveness of the isolated aortic rings to phenylephrine (PE) was tested. In addition, biochemical markers for oxidative stress such as plasma levels of lipid peroxides and total thiols, as well as the activities of erythrocytic superoxide dismutase (SOD) and whole blood glutathione peroxidase (GSH-Px) were assessed. Results of the present study indicated that induction of hyperglycaemia was associated with increased aortic ring responsiveness to PE, loss in body weight, increase in urine volume, elevation of plasma total thiols and lipid peroxide levels and elevated SOD and GSH-Px enzymatic activities. Treatment of normal rats with AG reduced the response of their aortae to PE. Furthermore, a profound increase in body weight without any significant change in the measured biochemical parameters was observed. In hyperglycaemic animals, AG tended to normalize the enhanced aortic response to PE and modulated STZ-induced biochemical changes without affecting the elevated plasma glucose level. Treatment of normal rats with DFO reduced the response of their aortae to PE and decreased their body weight without altering any of the chosen biochemical parameters. In hyperglycaemic animals, DFO attenuated the responsiveness of their aortae to PE and at the same time, did not affect the loss in body weight and the elevation of plasma glucose level observed in the hyperglycaemic group. Additionally, DFO normalized the elevated plasma level of total thiols and exerted a modulatory influence on the enhanced activities of SOD and GSH-Px as well as on the increased levels of lipid peroxides. Our data lend further credence for the contribution of oxidative stress in the vascular and biochemical changes associated with STZ-induced hyperglycaemia. It is also apparent that advanced glycosylation end products and nitric oxide might be involved. Until clinical studies prove the efficacy and safety of these drugs, specific agents which could scavenge free radicals and block protein glycosylation seem beneficial as a helpful adjunct to the therapy of diabetes.

Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic rats.

In light of evidence that some complications of diabetes mellitus may be caused or exacerbated by oxidative damage, we investigated the effects of subacute treatment with the antioxidant quercetin on tissue antioxidant defense systems in streptozotocin-induced diabetic Sprague-Dawley rats (30 days after streptozotocin induction). Quercetin, 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-1-benzopyran-4-one, was administered at a dose of 10mg/kg/day, ip for 14 days, after which liver, kidney, brain, and heart were assayed for degree of lipid peroxidation, reduced and oxidized glutathione content, and activities of the free-radical detoxifying enzymes catalase, superoxide dismutase, glutathione peroxidase, and glutathione reductase. Treatment of normal rats with quercetin increased serum AST and increased hepatic concentration of oxidized glutathione. All tissues from diabetic animals exhibited disturbances in antioxidant defense when compared with normal controls. Quercetin treatment of diabetic rats reversed only the diabetic effects on brain oxidized glutathione concentration and on hepatic glutathione peroxidase activity. By contrast, a 20% increase in hepatic lipid peroxidation, a 40% decline in hepatic glutathione concentration, an increase in renal (23%) and cardiac (40%) glutathione peroxidase activities, and a 65% increase in cardiac catalase activity reflect intensified diabetic effects after treatment with quercetin. These results call into question the ability of therapy with the antioxidant quercetin to reverse diabetic oxidative stress in an overall sense.

Retinoic acid treatment abrogates elastase-induced pulmonary emphysema in rats.

Pulmonary emphysema is a common disease in which destruction of the lung's gas-exchange structures (alveoli) leads to inadequate oxygenation, disability and frequently death; lung transplantation provides its only remediation. Because treatment of normal rats with all-trans-retinoic acid increases the number of alveoli, we tested whether a similar effect would occur in rats with emphysema. Elastase was instilled into rat lungs, producing changes characteristic of human and experimental emphysema: increased lung volume reflecting a loss of lung elastic recoil, larger but fewer alveoli and diminished volume-corrected alveolar surface area due to destruction of alveolar walls. Treatment with all-trans-retinoic acid reversed these changes providing nonsurgical remediation of emphysema and suggesting the possibility of a similar effect in humans.

Induction of muscle glutamine synthetase gene expression during endotoxemia is adrenal gland dependent.

Skeletal muscle plays a crucial role in maintaining nitrogen homeostasis during health and critical illness by exporting glutamine, the most abundant amino acid in the blood. We hypothesized that induction of glutamine synthetase (GS) expression, the principal enzyme of de novo glutamine biosynthesis, in skeletal muscle after endotoxin administration was adrenal gland dependent. We studied the expression of GS in normal and adrenalectomized rats after intraperitoneal administration of Escherichia coli lipopolysaccharide (LPS). Treatment of normal rats with LPS resulted in a marked increase in GS mRNA that was dose and time dependent, and preceded the increase in GS protein and specific activity. The increase in muscle GS mRNA observed in normal rats in response to LPS was abrogated in adrenalectomized rats at 3 h after high dose LPS treatment and markedly attenuated at 5.5 h after low dose LPS treatment. These and other studies implicate glucocorticoid hormones as a key, but not exclusive, regulator of skeletal muscle GS expression after a catabolic insult.

Effects of peroxisome proliferators and/or hypothyroidism on xenobiotic-metabolizing enzymes in rat testis

The objectives of the present work were to study the effects of certain peroxisome proliferators on xenobiotic-metabolizing enzyme activities in the testes of normal and hypothyroid rats, i.e. phenol sulfotransferases (pST), phenol UDP-glucuronosyl transferases (pUDPGT), glutathione transferases (GST), catalase, epoxide hydrolase (EH), glutathione peroxidase (GPX) and NAD(P)H quinone oxidoreductase (QR). Adult male rats (normal and hypothyroid) were treated for 10 days with clofibrate (0.5%), perfluorooctanoic acid (0.05%, PFOA), acetylsalisylic acid (1%, ASA) and di(2-ethylhexyl)phthalate (2%, DEHP) in their diet. The results show that treatment of normal rats with peroxisome proliferators dramatically affects the activities of xenobiotic-metabolizing enzymes (40–60% reduction). The highest effects are seen in catalase activity (50–60% with PFOA and ASA), pUDPGT (55% with PFOA), pST (55% with PFOA) and QR (50% with DEHP). These effects are not seen or are weaker after induction of hypothyroidism. Taken together, it is concluded that different classes of peroxisome proliferators have different effects on rat testicular xenobiotic-metabolizing enzymes.

Effects of enhanced striatal dopamine turnover in vivo on glutathione oxidation.

In Parkinson's disease (PD), a compensatory increase in dopamine (DA) turnover occurs in the remaining nigrostriatal dopaminergic neurons, resulting in greater exposure of each neuron to hydrogen peroxide (H2O2) derived from oxidative deamination of DA. The formation of oxyradicals from H2O2 is regarded as a mechanism that could contribute to the progression of PD, and incubation of rat striatal synaptosomes with levodopa (LD) results in an increase in oxidized glutathione (GSSG), indicative of oxidant stress. The present study was undertaken to determine whether striatal GSSG levels increase in response to administration of LD in vivo. Acute and repeated (3-week) treatment of normal rats with LD at doses of up to 100 mg/kg did not increase striatal GSSG despite marked increase in DA turnover. These results suggest that intact striatum may possess increased defense capacity against oxidant stress generated by increased DA turnover as compared with isolated synaptosomes.

Interrelation between renin mRNA levels, renin secretion, and blood pressure in two-kidney, one clip rats.

To examine the interrelation between renin mRNA levels, renin secretion, and blood pressure in rats, we clipped the left renal arteries of rats and measured renin mRNA levels in both kidneys, plasma renin activity, and blood pressure. One and 2 days after clipping, renin mRNA levels increased 3-fold and 4.3-fold in the stenosed kidney and were suppressed to 52% and 26% of controls in the intact kidneys; plasma renin activity increased from 8 to 16.5 and to 30.5 ng angiotensin I.h-1.mL-1 and systolic blood pressure rose from 114 to 123 and to 137 mm Hg. We found a strong correlation (P < .001) between plasma renin activity and renin mRNA levels in the clipped kidneys. We also found significant correlations (P < .05) between mRNA levels in the clipped and intact kidneys and between plasma renin activity and blood pressure for the individual animals. Treatment of normal rats with the converting enzyme inhibitor ramipril (5 mg/kg twice a day) for 2 days increased renin mRNA levels in both kidneys fourfold. In animals with unilateral clips, additional treatment with ramipril increased renin mRNA levels 6.4-fold in the stenosed and 3.3-fold in the intact kidneys. These findings suggest that endogenous angiotensin II exerts an inhibitory effect on renin mRNA expression in normal kidneys, clipped kidneys, and their contralaterals. Suppression of the renin gene in contralateral kidneys seems not to be directly mediated by the rise of plasma renin activity or by the rise of blood pressure in two-kidney, one clip rats.

In vivo administration of interleukin-1α induces muscle proteolysis in normal and adrenalectomized rats

The effect on muscle protein turnover of recombinant interleukin-1α (rlL-1α), 300 μg/kg body weight (BW) administered intraperitoneally (IP) in three divided doses over 18 hours, was studied in rats. Protein synthesis rate was determined by measuring incorporation of 14C-phenylalanine into protein, and total and myofibrillar protein breakdown rates were determined by measuring release of tyrosine and 3-methylhistidine, respectively, in incubated extensor digitorum longus muscles. To assess the role of glucocorticoids in rlL-1α-related metabolic alterations, plasma levels of corticosterone following rlL-1α injection and the effect of rlL-1α on muscle protein breakdown in adrenalectomized and sham-adrenalectomized rats were determined. Total and myofibrillar protein breakdown rates were increased by 45% and 167%, respectively, following treatment of normal rats with rlL-1α; muscle protein synthesis was not altered by the cytokine. Plasma corticosterone levels were markedly elevated following rlL-1α injection, with a maximal level occurring at 30 minutes. However, administration of rlL-1α resulted in increased total and myofibrillar protein breakdown rates in both adrenalectomized and shamadrenalectomized rats. The results suggest that increased muscle proteolysis following administration of rlL-1α is independent of glucocorticoids.