Role of Atrial Natriuretic Peptide in Oxytocin Induced Cardioprotection

Background The purpose of this study was to determine whether endogenous atrial natriuretic peptide (ANP) contributes to the protective effect of neurohypophysial hormone oxytocin (OT) in heart preconditioning. Methods Sprague-Dawley male rats were subjected to 25 min regional ischaemia and 120 min reperfusion and were divided into eight groups. Oxytocin or an equivalent volume of saline was administrated intraperitoneally, 30 min before ischaemia. The OT receptor antagonist (atosiban), ANP receptor antagonist (anantin) and nitric oxide synthase inhibitor (L-NAME) were injected 10 min before OT. In other groups, atosiban, anantin and L-NAME were only administered 40 min prior to ischaemia. Results Compared with the ischaemia/reperfusion group (I/R), alterations in infarct size, biochemical parameters LDH (lactate dehydrogenase), CK-MB (creatine kinase-MB), MDA (malondialdehyde) plasma levels] and severity of ventricular arrhythmia due to I/R injury were attenuated and VF was abolished by OT treatment. These OT effects were eliminated by OT and ANP receptor blockers and nitric oxide synthase inhibitor, but anantin did not reverse the effect of OT in lipid peroxidation. Conclusions These findings demonstrate an important contributory role of ANP in the OT induced protection in myocardial ischaemia reperfusion. OT also reduced lipid peroxidation with a NO-dependent mechanism

The Role of Oxytocin on Cardiac Ischemia-ReperfusionInduced Oxidative Stress in Rats

Abstract Introduction: Oxidative stress is caused by the imbalance between production of pro-oxidants and the antioxidant defenses. Reactive oxygen species (ROS) can play an important role in the pathogenesis of cardiovascular diseases. The present study aimed at investigating whether administration of oxytocin ameliorates oxidative stress induced by experimental myocardial infarction in rats. Materials and Methods: Cardiac ischemia-reperfusion (I/R) was induced by occlusion of left main coronary artery of rats for 25 min, followed by a period of reperfusion for 2h. OT at doses of 0.0001-1 µg was administered intraperitoneally 30 min prior to ischemia. Following reperfusion, blood samples were taken for measuring the plasma MDA levels, as an index of lipid peroxidation. Results: We observed a dose-dependent association between dose of oxytocin and plasma MDA. Oxytocin 0.01µg significantly reduced MDA levels as compared to control group. Blockade of specific OT receptors by atosiban attenuated the anti-oxidative effect of OT. The MDA level in the L-NAME and atropine groups were higher than those in the OT group and reach to control group, whereas the MDA levels in the anantin group were same as OT group and significantly lower than those in the control group. Conclusions: Oxytocin has a beneficial effect, mediated by NO and Ach, on cardiac tissue against oxidative damage due to I/R, suggesting that oxytocin can be used to tissue protection against oxidative stress

The Possible Mechanisms of the Impaired Insulin Secretion in Hypothyroid Rats.

Although the insulin secretion deficit in hypothyroid male rats has been documented, the underling mechanisms of the effect of hypothyroidism on insulin secretion are not clear. Isolated islets of the PTU-induced hypothyroid and control rats were exposed to glibenclamide, acetylcholine, and nifedipine in the presence of glucose concentrations of 2.8 or 8.3 and 16.7 mmol/L. Glucokinase and hexokinase specific activity, glucokinase content, and glucose transporter 2 protein expression were also determined in the isolated islets. Isolated islets from the hypothyroid rats showed a defect in insulin secretion in response to high glucose. In the presence of glibenclamide or acetylcholine, the isolated islets from the hypothyroid and control rats stimulated by glucose concentration of 16.7 mmol/L secreted similar amounts of insulin. In the presence of glucose concentrations of 8.3 mmol/L and 16.7 mmol/L, nifedipine was able to diminish insulin secretion from isolated islets of both groups, indicating that probably the defect may not arise from L type calcium channels or the steps beyond depolarization or the elements involved in the acetylcoline signaling pathway. Glucokinase content and hexokinase specific activity were also the same in the control and hypothyroid groups. On the other hand, glucokinase specific activity and glucose transporter 2 protein expression were significantly (p<0.001 and p<0.01 respectively) lower in the islets isolated from the hypothyroid rats (6.50 ± 0.46 mU/min/mg protein and 0.55 ± 0.09 arbitrary unit) compared to the controls (10.93 ± 0.83 mU/min/mg protein and 0.98 ± 0.07 arbitrary unit) respectively. In conclusion, the results of this study indicated that hypothyroidism reduced insulin secretion from isolated pancreatic islets, which confirms the finding of the previous studies; in addition, the insulin secretion deficit observed in hypothyroid rats may arise from the abnormalities in some parts of the glucose sensor apparatus of the pancreatic islets including glucokinase activity and glucose transporter 2 protein expression

Gestational hypothyroidism-induced changes in L-type calcium channels of rat aorta smooth muscle and their impact on the responses to vasoconstrictors

Objective(s): Thyroid hormones play an essential role in fetal growth and maternal hypo-thyroidism which leads to cardiovascular deficiency in their offspring.  Considering this, we intended to investigate the impact of gestational hypothyroidism on offspring vascular contractibility and possible underlying mechanisms. Materials and Methods: Hypothyroidism was induced in female rats by administration of 6-n-propyl-2-thiouracil in drinking water (0.02%) till delivery. The offspring aorta smooth muscle (without endothelium) contractile response to KCl (10-100 mM), KCl in the presence of nifedipine (10-4-10-1 µM), phenylephrine (10-9-10-6 M) and finally, phenylephrine and caffeine 100 mM in Ca2+-free Krebs were measured.    Results: KCl and phenylephrine-induced contractions were considerably lower in gestational hypothyroid (GH) than euthyroid offspring. GH responded to nifedipine with less sensitivity than control. The GH and control groups produced almost equal contraction in respond to phenylephrine and caffeine in Ca2+-free Krebs.  Conclusion: This study suggests that in hypothyroid offspring L-type Ca2+ channels are less functional, while intracellular Ca2+ handling systems are less modified by low levels of maternal thyroid hormones

Effects of stress related acute exercise on consolidation of implicit motor memory

Introduction: Extensive evidence documents arousal modulation of declarative memory in humans. However, little is known about the arousal modulation of implicit motor memory. The purpose of this study was to examine the effects of a post-acquisition acute exercise stress on implicit motor memory consolidation.Materials and Methods: Forty healthy subjects were randomly divided into stress (10 men and 10 woman) and non- stress (10 men and 10 woman) groups. Experiment consisted of two phases of acquisition and retention. Serial Color matching (SCM) task was used for this study. In acquisition period, all groups practiced the task for six blocks of 150 trials. Following, the stress group performed exercise on a treadmill until the moment of exhaustion while the non stress group did rest. In retention, all groups practiced the SCM task in one block. During the experiment the trends of saliva cortisol changes were measured.Results: Acute exercise stress leads to a significant increase in salivary cortisol level. While the non-stress group did not show enhancement of SCRT learning across the 24 hours delay interval, the stress group showed substantial enhancement across the same time (P<0.05).Conclusion: Our findings indicate that acute stress after acquisition can facilitate the implicit motor memory consolidation

Hexokinase and glucokinase specific activity.

<p>Each bar presents the mean±SEM from 9 cups of 9 rats. Each cup contained 300 islets in 400 μL of lysis buffer. Differences were analyzed by unpaired t test. ***<i>p</i><0.001, represents statistically significant differences, the PTU induced hypothyroid rats versus the controls.</p

Water consumption and food intake of the animals during the experiment period.

<p>In (A) and (B), each point represents the average amounts of daily water consumption and food intake of the rats in each cage respectively (three/cage). Data are expressed as mean±SEM. A significant difference was assessed by two-way ANOVA and Bonferoni post-test. * p<0.001, represents statistically significant difference, the PTU Induced hypothyroid (7 cages) versus the controls (7 cages). In (C), each bar represents percentage of food intake in the hypothyroid rats relative to the controls. A significant difference was assessed by unpaired t test. * p<0.001, represents statistically significant difference, between the hypothyroid rats food intake in the first and in the last 6 days of the experiment period.</p

Insulin secretion by islets in different glucose concentrations.

<p>Each bar presents the mean±SEM from 12–15 batches of eight islets from 5 or 6 rats, incubated for 60 min in 1 ml of medium containing different glucose concentrations. Differences were analyzed by Mann Whitney test. *<i>p</i><0.05, **<i>p</i><0.01, represent statistically significant differences, the PTU induced hypothyroid rats versus the controls.</p

Western blot analysis of GLUT2 protein in isolated islets in hypothyroidism.

<p>Data are expressed as mean±SEM from 10 protein bands of 5 rats in each group. Unpaired t test. **<i>p</i><0.01, represents statistically significant difference, the PTU induced hypothyroid rats versus the controls.</p