Contractility In Rats Research Articles

The Effects of Short- and Long-Term Ingestion of Plastic Toxin Bisphenol A on Gastrointestinal Transit Time in Rats.

Introduction Exposure to bisphenol A (BPA), a toxic chemical released from plastic, affects various body functions, including reproduction, metabolism, and development. The most common route of exposure to BPA is oral, and the gastrointestinal(GI) tract is, therefore, the first body system to be exposed to BPA. BPA has been well-documented to impair gut contractility in rats, in vitro. It may therefore be hypothesized that BPA may adversely affect GI motility and hence slow down the movement of food, resulting in the increased transit of food bolus in the GI tract. There are no reports so far on the effects of BPA on GI transit time. Objectives The present study was undertaken to examine the impact of exposure to BPA by a single oral dose (termed as short-term ingestion of BPA) and chronic (28-day) oral dose (termed as long-term ingestion of BPA) on the transit time of food bolus in the gut of adult male albino rats. Methods and materials The study was conducted in the Department of Physiology,Institute of MedicalSciences,Banaras Hindu University, Varanasi,Uttar Pradesh, India. In one set of experiments, each animal was fed a food pellet, once (short-term ingestion) containing BPA (2 µg/kg and 50 µg/kg in different groups), and in another set of experiments, each animal was fed a food pellet containing BPA (50 µg/kg/day) for 28 consecutive days (long-term ingestion). Control rats in both sets were fed food pellets without BPA. Subsequently, the gastric transit index (GTI), ileocecal transit index (ICTI), and colonic transit time (CTT) were determined by the standard charcoal marker method. Results One-time ingestion of a food pellet containing BPA caused a significant (p < 0.05) drop in the GTI and ICTI and an increase in the CTT with both doses of BPA (2 and 50 µg/kg). Similarly, after chronic (28-day), oral BPA exposure, a significant decrease in the GTI and ICTT and an increase in CTT were observed. Conclusion Both short-term (one-time) and long-term (28-day) oral exposure to BPA-containing food harmed GI transit. Slow GI transit may lead to metabolic disorders and GI motility disorders, such as constipation.

The effects of nickel chloride on papillary muscle contractility under normothermic and hypothermic conditions: Comparison of active and hibernating ground squirrels (Urocitellus undulatus) with Wistar rats.

Extracellular Ca2+ plays a pivotal role in the regulation of cardiac contractility under normal and extreme conditions. Here, by using nickel chloride (NiCl2), a non-specific blocker of extracellular Ca2+ influx, we studied the input of extracellular Ca2+ on the regulation of papillary muscle (PM) contractility under normal and hypothermic conditions in ground squirrels (GS), and rats. By measuring isometric force of contraction, we studied how NiCl2 affects force-frequency relationship and the rest effect in PM of these species at 30 °C and 10 °C. We found that at 30 °C 1.5 mM NiCl2 significantly reduced force of contraction across entire frequency range in active GS and rats, whereas in hibernating GS force of contraction was reduced at low and high frequency range. Additionally, NiCl2 evoked spontaneous contractility in rats but not GS PM. The rest effect was significantly reduced by NiCl2 for active GS and rats but not hibernating GS. At 10 °C, NiCl2 fully reduced contractility in active GS and, to a lesser extent, in rats, whereas in hibernating GS it was significant only at 0.3 Hz. The rest effect was significantly reduced by NiCl2 in both active and hibernating GS, whereas it was unmasked in rats that had high contractility under hypothermic conditions in control. Our results show a significant contribution of extracellular Ca2+ to myocardial contractility in GS not only in active but also in hibernating states, especially under hypothermic conditions, whereas limitation of extracellular Ca2+ influx in rats under hypothermia can play protective role for myocardial contractility.

Acute Exposure to Bisphenol S Decreases In Vitro Right Atrial Contractility in Rats.

Bisphenols are widely used in the manufacturing of polycarbonate material and epoxy resins which constitute the essential component of plastic. Bisphenol A (BPA) has been reported to produce toxicity on organs in both animal and human studies. Therefore, plastic manufacturers are replacing BPA with other analogues that are considered to be safe, and BPA-free products are now available in the market. However, some studies have reported that bisphenol-S (BPS) also possesses toxic properties. It has been reported to depress ventricular contraction as well as produce ventricular arrhythmia on acute exposure. The present study was performed to examine the effect of BPS on in vitro spontaneously-beatingright atria in rats. In the present study, in vitro spontaneous contractions of right atria obtained from adult female rats of the Wistar strain were recorded. The atria were exposed to BPS (10-6-10 mM) and its effects on atrial contractions were recorded in the form of cumulative-concentration response with and without administration of antagonists namely atropine, L-NAME, and methylene blue. BPS decreased the rate as well as the force of atrial contractions. Thechanges produced in the rate and force of atrial contractions were not attributed to ethanol, which was used to prepare BPS solutions. The decrease in right atrial contractility produced by BPS was blocked by L-NAME; however, atropine and methylene blue were not able to antagonize the effects of BPS on atria. The present studyindicates the involvement of NO-dependent but cGMP independent pathway responsible forBPS-induced cardio-toxicity.

Lead acetate versus cadmium sulfate in the modulation of main physiological pathways controlling detrusor muscle contractility in rat

Heavy metals have a deleterious effect on lower urinary tract functions. Scant data has been reported about metals’ effect on altering detrusor muscle contractility. Rats were given lead acetate (3, 30 mg/kg), cadmium sulfate (0.1, 1 mg/kg) or ferrous sulfate-iron overload-(3, 30 mg/kg), in a subacute toxicity study (21 days, ip). In-vitro tension experiments were conducted using isolated rat detrusor muscle. Measurement of heavy metal concentrations in blood and tissue homogenates was performed, as well as histopathological examinations. Subacute toxicity induced by treatment with lead and cadmium was manifested as a decrease in EFS, ACh, and ATP-mediated contraction of isolated detrusor muscle. Iron overload only decreased EMAX of EFS and ACh-mediated contraction. Lead (30 mg/kg) caused an upward shift in the dose response curve of isoprenaline-induced relaxation, with a significant decrease in EMAX. Lead (30 mg/kg) or cadmium (1 mg/kg) inhibited adenosine (10−5 M)-induced relaxation. Comparisons to control tissues showed a selective accumulation of metals in the detrusor muscle. Histopathological examinations revealed edema and inflammation in the urinary bladder. Directly added lead (10 mM) inhibited detrusor muscle contraction in-vitro, and its effect was decreased in presence of atropine, and potentiated in presence of TEA, L-NAME, or MB. Cadmium's (0.1 mM) inhibitory effect was reduced in presence of nifedipine or trifluoperazine. In conclusion, lead, cadmium, or iron induce detrusor hypoactivity: The inhibitory effect of lead may be mediated by modulating muscarinic receptors but not the K+/NO/cGMP pathway, whereas cadmium inhibitory effect may be mediated by inhibiting the Ca2+/calmodulin pathway.

Galectin-3 inhibits cardiac contractility via a tumor necrosis factor alpha-dependent mechanism in cirrhotic rats.

Background/AimsGalectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy – related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy.MethodsRats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy.ResultsGalectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls.ConclusionIncreased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.

Linalyl acetate restores colon contractility and blood pressure in repeatedly stressed-ulcerative colitis rats.

BackgroundUlcerative colitis (UC) is related to stress, but few studies have evaluated the influence of stress on factors affecting colon contractility in rats with UC. Also, there have been no studies investigating beneficial effects of linalyl acetate (LA), the major component of lavender essential oil, in repeatedly stressed-ulcerative colitis rats. Therefore, we investigated the differences in factors affecting colon contractility of UC rats with or without repeated restraint stress (RRS) and the effects of LA on these parameters in repeatedly stressed-UC rats.MethodsRats were assigned to following groups: control, RRS, UC, RRS+UC, and RRS+UC treated with LA or sulfasalazine. To induce UC, rats were administered 2% dextran sodium sulfate (DSS) water on days 1–5, followed by tap water on days 6–15 and DSS water on days 16–20. RRS was induced by immobilizing rats for 2 hr/day on days 1–20. LA or sulfasalazine were daily administered on days 16–20.ResultsDisease activity index (DAI) was markedly increased in RRS+UC. Serum interleukin-6 levels and acetylcholine-induced colon contraction were higher in RRS+UC than in control, RRS and UC. Colon nitrite levels also significantly increased in RRS+UC compared to the control and RRS. Blood pressure (BP) was higher in RRS+UC than in the control and UC. Both LA and sulfasalazine was effective in decreasing DAI, colon nitrite levels, acetylcholine-induced colon contraction in RRS+UC. Sulfasalazine significantly reduced serum IL-6 levels in RRS+UC with decreasing tendency in RRS+UC treated by LA. Only LA significantly reduced BP in RRS+UC.ConclusionsOur findings emphasize the importance of stress management in UC patients. Also, LA may be beneficially used in repeatedly stressed-UC patients with high BP.

Effect of agomelatine on intestinal smooth muscle contractility in rats

Objective: The purpose of the present study was to investigate in vitro the effect of agomelatine, an analog of melatonin, on KCl-stimulated contractions in duodenum, jejunum, ileum, and colon in rats. Material and methods: A total of 7 adult Wistar Albino female rats were used in the study. After the rats were decapitated without anesthesia, duodenum, jejunum, ileum, and colon strips were prepared and placed in the organ bath. Agomelatine was applied in doses of 100, 200, and 1000 μM to the strips that were contracted with KCl (80 mM). Then, 1000 μM agomelatine was applied after preliminary treatment of melatonin receptor antagonist luzindole (1 μM) to investigate the action mechanism of agomelatine on intestinal smooth muscles. The records were analyzed before and after each dose, and frequency, peak to peak (P-P) and area values were compared. Results: Agomelatine inhibited the KCI- induced contractions in duodenum, jejunum, ileum, and colon strips in a dose-dependent manner. Depending on the agomelatine application, the frequency, “P-P”, and the area values under the curve decreased at statistically significant levels (p&lt;0.05). However, the effect of agomelatine decreased at significant levels as a result of luzindole treatment (p&lt;0.05). Conclusion: The dose-dependent inhibitor effect of agomelatine on KCl-stimulated contractions in the rat intestinal smooth muscle was shown for the first time in this study. Agomelatine was found to affect the smooth muscles of the intestines through melatonin receptors. This result suggests that agomelatine might have therapeutic potential in diseases in which gastrointestinal motility is impaired.

Improved bladder contractility after transplantation of human mesenchymal stem cells overexpressing hepatocyte growth factor into underactive bladder from bladder outlet obstruction models of rats.

IntroductionAn underactive bladder can lead to difficulty in voiding that causes incomplete emptying of the bladder, suggesting the need for a new strategy to increase bladder contractility in such patients. This study was performed to investigate whether human mesenchymal stem cells (hMSCs) were capable of restoring bladder contractility in rats with underactive bladder due to bladder outlet obstruction (BOO) and enhancing their effects by overexpressing hepatocyte growth factor (HGF) in hMSCs.Materials and methodsThe hMSCs were transplanted into the bladder wall of rats. Fifty female Sprague-Dawley rats at six weeks of age were divided into five groups: group 1: control; group 2: sham intervention; group 3: eight-week BOO; group 4: BOO rats transplanted with hMSCs; and group 5: BOO rats transplanted with hMSCs overexpressing HGF. Two weeks after the onset of BOO in groups 4 and 5, hMSCs were injected into the bladder wall. Cystometry evaluation was followed by Masson’s trichrome staining of bladder tissues. Realtime PCR and immunohistochemical staining were performed to determine for hypoxia, apoptosis, and angiogenesis.ResultsCollagen deposition of bladder increased in BOO but decreased after transplantation of hMSCs. The increased inter-contraction interval and residual urine volume after BOO was reversed after hMSCs transplantation. The decreased maximal voiding pressure after BOO was restored by hMSCs treatment. The mRNA expression of bladder collagen1 and TGF-β1 increased in BOO but decreased after hMSCs transplantation. The decrease in vWF-positive cells in the bladder following BOO was increased after hMSCs transplantation. Caspase 3 and TUNEL-positive apoptosis of bladder cells increased in BOO but decreased after transplantation of hMSCs. These effects were enhanced by overexpressing HGF in hMSCs.ConclusionTransplantation of hMSCs into bladder wall increased the number of micro-vessels, decreased collagen deposition and apoptosis of detrusor muscle, and improved bladder underactivity. The effects were enhanced by overexpressing HGF in hMSCs. Our findings suggest that the restoration of underactive bladder using hMSCs may be used to rectify micturition disorders in patients following resolution of BOO. Further studies are needed before hMSCs can be used in clinical applications.

Apoptotic Bodies of Cardiomyocytes and Fibroblasts - Regulators of Directed Differentiation of Heart Stem Cells.

We studied the effects of apoptotic bodies of cardiomyocytes (ApBc) and fibroblasts (ApBf) on myocardial regeneration and contractility in rats and the dynamics of RNA concentrations in cardiomyocytes and fibroblasts at different stages of apoptosis. ApBc increase the contractility of rat myocardium, while ApBf reduce it. ApBc stimulate the development of clones of cardiomyocyte precursors in the myocardium, while ApBf stimulate the formation of endothelial precursor clones. In doxorubicin cardiomyopathy, ApBc, similar to the reference drug (ACE inhibitor) improve animal survival, while ApBf produce no such effect. RNA concentrations in cardiomyocytes and fibroblasts before apoptosis and at the beginning of cell death significantly differed, while in apoptotic bodies of these cells, it was practically the same. It has been hypothesized that RNA complex present in ApBc and ApBf represents an "epigenetic code" of directed differentiation of cardiac stem cells.

Non-genomic actions of sex hormones on pregnant uterine contractility in rats: An in vitro study at term

AimsThe non-genomic (prompt) actions of sex steroids on pregnant uterine contractility are not fully explored yet, the aim of our study was to clarify such effects of 17-β estradiol (E2), progesterone (P4) and testosterone (T) on late (22-day) pregnant uterine contractions together with the signaling pathways in rats in vitro. MethodsThe uterine effects of sex steroids on KCl-stimulated contractions were examined in the presence of genomic pathway blocker actinomycin D and cycloheximide, sex hormone receptor antagonists (flutamide, fulvestrant, mifepristone) and also after removing the endometrium. The modifications in uterine G-protein activation and cAMP levels were also detected. ResultsT and E2 both relaxed the uterine contractions in the concentration range of 10−8–10−3 M with an increase in the activated G-protein and cAMP levels of the uterus, while P4 was ineffective. Cycloheximide, actinomycin D, antagonist for T and E2 were not able to modify the responses along with the endothelium removal. Mifepristone blocked the relaxing effects of T and E2 and reduced the activation of G-protein and the formation of cAMP. SignificanceT and E2 can inhibit KCl-stimulated contractions in the late pregnant uterus in high concentrations and in a non-genomic manner. Their actions are mediated by a G-protein coupled receptor that can be blocked by mifepristone. A single and high dose of T or E2 might be considered in premature contractions, however, further preclinical and clinical studies are required for the approval of such a therapeutic intervention.

Protective effect of quercetin against myocardial ischemia as a Ca2+ channel inhibitor: involvement of inhibiting contractility and Ca2+ influx via L-type Ca2+ channels.

Many studies describe the stimulating effect of quercetin on Ca2+ channels and the treatment of cardiovascular diseases such as myocardial ischemia and hypertension. However, these studies are scattered and contradictory. The aim of this study is to elucidate the protective effects of quercetin against isoproterenol (ISO)-induced myocardial ischemia and verify the cellular mechanisms based on the L-type Ca2+ channel (LTCC), Ca2+ transients, and myocardial contractility. An animal model of myocardial ischemia was established by subcutaneous injection of ISO for 2days. Quercetin significantly reduced J-point elevation, heart rate, reactive oxygen species, serum levels of myocardial enzymes, superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione S-transferase and improved heart pathologic morphology. L-type Ca2+ current (ICa-L) was tested in an experiment with isolated rat myocardial cells by using the whole-cell patch-clamp recording technique and IonOptix Myocam detection system. Quercetin reduced ICa-L in a concentration-dependent fashion with a half-maximal inhibitory concentration of 4.67 × 10-4M. Quercetin also shifted the current-voltage curve upwards, moved the activation and inactivation curves to the left and inhibited the amplitude of the cell shortening and Ca2+ transients. The results showed that quercetin acts as a LTCC inhibitor and exerts a cardioprotective effect by inhibiting Ca2+ influx and contractility in rats.

MARCKS mediates vascular contractility through regulating interactions between voltage-gated Ca2+ channels and PIP2

Phosphatidylinositol 4,5-bisphosphate (PIP2) acts as substrate and unmodified ligand for Gq-protein-coupled receptor signalling in vascular smooth muscle cells (VSMCs) that is central for initiating contractility. The present work investigated how PIP2 might perform these two potentially conflicting roles by studying the effect of myristoylated alanine-rich C kinase substrate (MARCKS), a PIP2-binding protein, on vascular contractility in rat and mouse mesenteric arteries. Using wire myography, MANS peptide (MANS), a MARCKS inhibitor, produced robust contractions with a pharmacological profile suggesting a predominantly role for L-type (CaV1.2) voltage-gated Ca2+ channels (VGCC). Knockdown of MARCKS using morpholino oligonucleotides reduced contractions induced by MANS and stimulation of α1-adrenoceptors and thromboxane receptors with methoxamine (MO) and U46619 respectively. Immunocytochemistry and proximity ligation assays demonstrated that MARCKS and CaV1.2 proteins co-localise at the plasma membrane in unstimulated tissue, and that MANS and MO reduced these interactions and induced translocation of MARCKS from the plasma membrane to the cytosol. Dot-blots revealed greater PIP2 binding to MARCKS than CaV1.2 in unstimulated tissue, with this binding profile reversed following stimulation by MANS and MO. MANS evoked an increase in peak amplitude and shifted the activation curve to more negative membrane potentials of whole-cell voltage-gated Ca2+ currents, which were prevented by depleting PIP2 levels with wortmannin. This present study indicates for the first time that MARCKS is important regulating vascular contractility and suggests that disinhibition of MARCKS by MANS or vasoconstrictors may induce contraction through releasing PIP2 into the local environment where it increases voltage-gated Ca2+ channel activity.

Two thalidomide analogs induce persistent estrous behavior and inhibit uterus contractility in rats: The central role of cAMP

The effects of 4NO2PDPMe and 4APDPMe, which are thalidomide (Tha) analogs that act as selective phosphodiesterase (PDE-4) inhibitors, on estrous behavior (lordosis and proceptive behaviors) and on uterine contraction were studied in ovariectomized (OVX) estrogen-primed Sprague Dawley (SD) and in intact non-pregnant Wistar rats, respectively. We found that intracerebroventricular (ICV) infusion of either 4NO2PDPMe or 4APDPMe (20 to 80 μg) stimulated intense lordosis and proceptive behavior in response to mounts from a sexually active male, within the first 4 h after infusion, and persisting for up to 24 h. Inhibitors of the progesterone receptor (RU486, administered subcutaneously), the estrogen receptor (tamoxifen, ICV), the adenylate cyclase (AC)/ cyclic AMP (cAMP)/protein kinase A (PKA) pathway (administered ICV), and the mitogen activated protein kinase (MAPK) pathway (administered ICV) significantly decreased lordosis and proceptive behavior induced by Tha analogs. Uterine contractility studies showed that Tha analogs inhibited both the K+- and the Ca2+-induced tonic contractions in rat uterus. Tha analogs were equally effective, but 4APDPMe was more potent than 4NO2PDPMe. These results strongly suggest the central role of cAMP in both processes, sexual behavior, and uterine relaxation, and suggest that Tha analogs may also act as Ca2+-channel blockers.

Su1625 – In Vivo and in Vitro Effects of Coffee on Gut Microbiota and Smooth Muscle Contractility in Rats

Su1625 – In Vivo and in Vitro Effects of Coffee on Gut Microbiota and Smooth Muscle Contractility in Rats

A selective inhibitor of mitofusin 1-βIIPKC association improves heart failure outcome in rats

We previously demonstrated that beta II protein kinase C (βIIPKC) activity is elevated in failing hearts and contributes to this pathology. Here we report that βIIPKC accumulates on the mitochondrial outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86. Mfn1 phosphorylation results in partial loss of its GTPase activity and in a buildup of fragmented and dysfunctional mitochondria in heart failure. βIIPKC siRNA or a βIIPKC inhibitor mitigates mitochondrial fragmentation and cell death. We confirm that Mfn1-βIIPKC interaction alone is critical in inhibiting mitochondrial function and cardiac myocyte viability using SAMβA, a rationally-designed peptide that selectively antagonizes Mfn1-βIIPKC association. SAMβA treatment protects cultured neonatal and adult cardiac myocytes, but not Mfn1 knockout cells, from stress-induced death. Importantly, SAMβA treatment re-establishes mitochondrial morphology and function and improves cardiac contractility in rats with heart failure, suggesting that SAMβA may be a potential treatment for patients with heart failure.

Impacts of prolonged chlorpyrifos exposure on locomotion and slow-and fast- twitch skeletal muscles contractility in rats.

Investigate the effect of dietary exposure to chlorpyrifos on locomotion and contraction of soleus andextensor digitorum longus (edl) involved in locomotion. Methods: Rats were fed diets containing 1 or 5 mg kg-1 of chlorpyrifos for six weeks. Locomotion has been assessed weekly using beam walking and beam balance tests. Soleus and edl were removed to study contractile properties, myofibrillar protein content and myosin heavy chain isoforms. Animals treated with 5 mg kg-1 chlorpyrifos had a decrease body weight. An increase by 28% and 24% in latency time assessed by beam walking test and a decrease by 9% and 13% in the beam balance time was reported after 6 weeks of 1 and 5 chlorpyrifos exposure respectively. The contractile properties in soleus showed an increase in twitch amplitude by 25% and 63% in 1 and 5 doses respectively, without modification in the contraction time and half relaxation time. edl treated with 1 mg kg-1 showed a decrease by 35%, 42% and 22% in twitch amplitude, contraction time and half relaxation time respectively. edl treated with 5 mg kg-1 showed an increase of 23% in twitch amplitude without modification of the other parameters. These changes were associated with modification of myofibrillar protein content in all treated groups. Myosin heavy chain isoforms were altered in both skeletal muscles treated with 1 mg kg-1. Exposure to chlorpyrifos can alter the locomotion and produce physiological changes in a dose and muscle type related manner.

The effect of bupivacaine on gastrocnemius muscle contractility in rats with diabetes

This study examined the changes in skeletal muscle contraction parameters after the injection of bupivacaine into the gastrocnemius muscle in diabetic rats. Forty male Wistar albino rats (230–270 g) were divided into four groups: Group I: Untreated healthy control; Group II: Healthy injected with Bupivacaine; Group III: Diabetic control; Group IV: Diabetic injected with bupivacaine. The diabetes was induced with streptozotocin in 0.1 M citrate buffer (pH 4.5) injection at 45 mg/kg in tail vein. On 7th day of streptozotocin injection, the rats in groups II and IV were injected with 0.25% bupivacaine at 8 mg/kg body weight into the gastrocnemius muscle. Three weeks post bupivacaine application, the animals were sacrificed and right leg gastrocnemius muscle was isolated for studying various parameters such as muscle twitch, tetanic force, contraction and relaxation time, and maximum contraction and relaxation rates. The blood glucose estimation showed that the rats in group III and IV developed diabetes at two days after administration of streptozotocin. The administration of bupivacaine resulted in a significant (p less than 0.05) increase in the muscle twitch parameters both in Group II and Group IV. Thus, bupivacaine can increase muscle contractility in diabetic muscles also.

Cardiac Hypertrophy and Ventricular Contractility in Rats Exposed to Neonatal Supplemental Oxygen and High Fat Diet

Premature birth represents about 13% of live births each year. Since lungs of these infants are underdeveloped, they receive supplemental oxygen right after birth, but little is known about its effects on the development of normal physiological responses and whether it impacts long‐term cardio‐metabolic function. Based on previous studies from our lab that showed increased pulse wave velocity in 12 month old rats exposed to neonatal supplemental oxygen, we hypothesized that neonatal exposure to supplemental oxygen causes cardiac hypertrophy and decreased left ventricular contractility. We also hypothesized that these effects to supplemental oxygen would be enhanced by 10 weeks on a high fat diet. To test the hypothesis, we used our rat model of OXY and CON rats exposed to FlO2=0.80 and 0.21 respectively, for 8 days post‐birth. Two months after birth, these OXY and CON rats were randomly assigned to either a high fat diet (60% of calories from animal fat) or low fat diet for 10 weeks during which their weights and caloric consumptions were monitored. After 10 weeks, a Miller conductance catheter was inserted into the left ventricle to obtain pressure volume loops and end‐systolic pressure volume relationship, which was used to evaluate contractility. OXY rats tended to have larger left ventricles (1.40±0.24 g vs 1.18±0.08g) and OXY rats fed a high fat diet showed greater average weight gain than CON rats on the same diet. There was no difference in contractility. These data suggest that neonatal supplemental oxygen may promote left ventricular hypertrophy and weight gain.Support or Funding InformationThe University of Iowa Start‐Up Fund

Adrenoceptors in Dopaminergic Regulation of Rat Myocardial Contractility in Rats During Ontogeny.

The effects of different dopamine concentrations on contractility of myocardium with blocked α- or β-adrenoceptors were examined in vitro in 21- and 100-day old rats. In myocardial strips with blocked α-adrenoceptors, dopamine (10-5 M) increased the right atrial contractile force. By contrast, this neurotransmitter (10-9-10-5 M) reduced the contractile force of atrial and ventricular strips with blocked β-adrenoceptors.

NPY1 Receptors Participate in the Regulation of Myocardial Contractility in Rats.

Selective agonist (Leu(31)Pro(34)NPY) and blocker (BIBP-3226) of NPY1 receptors were used to determine the type of NPY receptors involved in myocardial contraction. Experiments with isometric contraction of myocardial strips from mature rats showed that the agonist produced the most potent effect in a concentration of 10-7 M. In this concentration, Leu(31)Pro(34)NPY showed the greatest positive inotropic effect on the contraction of the atria and ventricles. In contrast, selective blocker BIBP-3226 reduced the force of myocardial contractions. Pretreatment of myocardial strips with this blocker abolished the positive inotropic effect of Leu(31)Pro(34)NPY, which attested to important role of NPY1 receptors in myocardial contraction.