Cell proliferation in the hippocampus and in the heart is modified by exposure to repeated stress and treatment with memantine.

The present studies were aimed to verify the hypothesis that treatment with memantine, a low affinity NMDA glutamate receptor antagonist, can reduce possible stress-induced alterations in cell proliferation in the hippocampus and in the heart and has consequences on stress hormone release. Adult male Wistar rats were exposed to repeated hypokinesis (movement restraint, 2 h daily) or remained undisturbed and they were treated with memantine (5 mg/kg/day, s.c.) or vehicle for 8 days. On the day 7, all animals were injected with 5-bromo-2'-deoxyuridine (BrdU), a marker of cell proliferation. The mild form of chronic stress used resulted only in moderate decrease in BrdU incorporation into DNA in the hippocampus, while the same stimulus caused a pronounced reduction of the new cells formed in left heart ventricle. In both tissues, stress-induced reduction in cell proliferation was more evident in memantine-treated rats. Memantine failed to modify hormones of the hypothalamic-pituitary-adrenocortical axis, while the treatment increased plasma renin activity. The present study demonstrates that treatment with memantine potentiated rather than prevented stress-induced reduction of cell proliferation. We have shown that stress exposure may induce a reduction in cell proliferation in the heart, even in a higher extent than that in the hippocampus. Effects of memantine under stress conditions might be relevant with respect to clinical use of memantine, which is being used in the treatment of neurodegenerative diseases.

Effect of Hemidesmus indicus on ischemia-reperfusion injury in the isolated rat heart.

The root extract of Hemidesmus indicus (Linn.) R. Br. (Asclepiadaceae) (HI) was studied for its cardioprotective effect in Langendorff-perfused rat hearts. HI was perfused for 15 min at a concentration of 0.09 g/L prior to 30 min global ischemia/120 min reperfusion (I/R). Recovery of functional parameters, reperfusion arrhythmias, and infarct size (TTC staining) served as the end-points. After 15 min of perfusion with HI, the left ventricular developed pressure (LVdevP) and HR (heart rate) were not altered significantly (p>0.05), as compared with the pre-drug values. During R, HI showed a significantly higher (p<0.05) recovery of LVdevP at nearly all time points. The recovery of maximal rate of pressure development (+dP/dtmax) and left ventricular end-diastolic pressure (LVEDP) at 40 min of R were significantly better than in non-treated controls. There was also a significant reduction in the total number of ventricular premature beats (VPB) and duration of ventricular tachycardia (VT). HI can protect ischemic myocardium against contractile dysfunction and reperfusion-induced arrhythmias and reduce the extent of irreversible tissue damage following I/R in rat hearts.

Neuroendocrine and cardiovascular parameters during simulation of stress-induced rise in circulating oxytocin in the rat.

Physiological functions of oxytocin released during stress are not well understood. We have (1) investigated the release of oxytocin during chronic stress using two long-term stress models and (2) simulated stress-induced oxytocin secretion by chronic treatment with oxytocin via osmotic minipumps. Plasma oxytocin levels were significantly elevated in rats subjected to acute immobilization stress for 120 min, to repeated immobilization for 7 days and to combined chronic cold stress exposure for 28 days with 7 days immobilization. To simulate elevation of oxytocin during chronic stress, rats were implanted with osmotic minipumps subcutaneously and treated with oxytocin (3.6 microg/100 g body weight/day) or vehicle for 2 weeks. Chronic subcutaneous oxytocin infusion led to an increase in plasma oxytocin, adrenocorticotropic hormone, corticosterone, adrenal weights and heart/body weight ratio. Oxytocin treatment had no effect on the incorporation of 5-bromo-2-deoxyuridine into DNA in the heart ventricle. Mean arterial pressure response to intravenous phenylephrine was reduced in oxytocin-treated animals. Decrease in adrenal tyrosin hydroxylase mRNA following oxytocin treatment was not statistically significant. Oxytocin treatment failed to modify food intake and slightly increased water consumption. These data provide evidence on increased concentrations of oxytocin during chronic stress. It is possible that the role of oxytocin released during stress is in modulating hypothalamic-pituitary-adrenocortical axis and selected sympathetic functions.