The effect of centrally administered erythropoietin on cardiovascular and respiratory system of anaesthetized rats.

Erythropoietin (EPO) is a hematopoietic factor, which is produced primarily by the adult kidney in response to tissue hypoxia. There is strong evidence that EPO may also be synthesized in the brain and act as a neuroprotector or neuromodulator in the central nervous system. The present study investigated the effect of centrally administered EPO on cardiovascular and respiratory parameters in anaesthetized rats. The animals were anaesthetized with ketamine (70 mg/kg) and xylazine (10 mg/kg) mixture. EPO at doses of 0.06, 0.12, 0.25 and 0.50 IU/5 microl or 0.9% saline as a control were injected intracerebroventricularly and blood pressure, heart rate, respiratory rate, tidal volume and minute ventilation were recorded. Following the administration of EPO, there was a significant increase in blood pressure, heart and respiratory rates, tidal volume and minute ventilation which were time and dose dependant. In order to investigate whether these effects of centrally injected EPO was caused by the diffusion of the drug to the periphery, the highest dose EPO (0.5 IU) in the present study, was injected intravenously but intravenously injected EPO showed no significant effect in these parameters. In conclusion, our findings showed that centrally injected erythropoietin caused pressor and tachycardic response, an increase in respiratory frequency and volume in anaesthetized rats. Moreover intravenous injection of the highest dose of EPO used in the study caused no effect suggesting a central mechanism of action for the agent. Hence, one can hypothesize that erythropoietin may play a role in the central regulation of cardiovascular and respiratory system as a neuromodulator or neuromediator.

The role of the central thromboxane A2 in cardiovascular effects of a phospholipase A2 activator melittin administrated intracerebroventricularly in normotensive conscious rats.

The current study was designed to determine the cardiovascular effect of centrally administrated melittin, a phospholipase A2 (PLA2) activator, and the mediation of central thromboxane A2 (TXA2) and its receptors in normotensive conscious rats. Studies were performed in normotensive male Sprague Dawley rats injected intracerebroventricularly (i.c.v.) with melittin. Melittin (1.5, 3.0, 6.0 microg/5.0 microl; i.c.v.) caused dose- and time-dependent increases in mean arterial pressure (MAP) and decrease in heart rate (HR). Maximal effects were observed 5-10 min after 3.0 microg dose of melittin. In order to test the mediation of central TXA2 and its central receptors in the cardiovascular effect of melittin, the rats were pretreated with furegrelate (500.0 microg; i.c.v.), a TXA2 synthesis inhibitor, and SQ-29548 (8.0 microg; i.c.v.), a TXA2 receptor antagonist, 15 min prior to melittin (3.0 microg). Furegrelate or SQ-29548 partially inhibited the pressor effect and bradycardia elicited by melittin. In conclusion, our findings show that centrally administered melittin increases MAP and decreases HR in conscious rats. Moreover, according to our findings, central TXA2 and its receptors may in part mediate melittin-induced cardiovascular effects.

Protective effects of long term dietary restriction on swimming exercise-induced oxidative stress in the liver, heart and kidney of rat.

In this study, we evaluated the hypothesis that long term dietary restriction would have beneficial effects on the oxidative stress and antioxidant enzyme systems in liver, heart and kidney in adult male rats undergoing different intensities of swimming exercise. Sixty male, Sprague-Dawley rats were assigned as either dietary restricted on every other week day (DR) or fed ad libitum (AL) groups, and each group was further subdivided into sedentary, endurance swimming exercise training (submaximal exercise) and exhaustive swimming exercise (maximal exercise) groups. Animals in the submaximal exercise group swam 5 days/week for 8 weeks, while maximal exercise was performed as an acute bout of exercise. In parallel with the increase in the intensity of the exercise, the degree of lipid peroxidation and protein oxidation were increased in both the DR and AL groups; however the rate of increase was lower in the DR group. Reduced glutathione (GSH), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) enzyme activities were lower in the DR group than in the AL group. In parallel with the increase in exercise intensity, GSH and GR enzyme activities decreased, whereas an increase was observed in GSH-Px enzyme activity. In conclusion, the comparison between the DR and AL groups with the three swimming exercise conditions shows that the DR group is greatly protected against different swimming exercise-induced oxidative stress compared with the AL group.