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Indian Journal of Pharmacology, Vol. 38, No. 4, July-August, 2006, pp. 281-282 Research Letter Effect of acute and chronic treatment of losartan potassium on tail-flick response in mice Pandi PV, Nagappa AN Pharmacy group, Birla Institute of Technology and Science, Pilani - 333 031, Rajasthan Code Number: ph06073 Antinociception is termed as a reduction in the response of pain sensory system to noxious stimuli. Repeated treatments of losartan (10 mg/kg) orally has been shown to increase the latency of paw withdrawal (in male Swiss albino mice) in the hot-plate test and the increase was reversed by naloxone. This suggests the involvement of brain angiotensin II (Ang II) in the central nociceptive mechanism, through an antagonistic interaction with the endogenous opioid system.[1] The hot-plate test is an experimental procedure that involves supraspinal components.[2] It is thus interesting to investigate whether losartan has the same antinociceptive effects when an experimental model, based on a different pain mechanism, is used. In the present study we investigated the tail-flick response to noxious heat, which is probably a spinal reflex.[2] The use of different models for measuring pain is important because the antinociceptive effects of losartan could be due to one or more mechanisms. Male Swiss albino mice, from the central animal facility of the Birla Institute of Technology and Science, Pilani, were used for the present study, after obtaining prior approval from IAEC. The animals, weighing 20-25 g, were housed in groups of 10 per cage, with free access to food and water, throughout the experiment. The tail-flick test, using a radiant heat source (Medicraft Analgesiometer Mark IV, Medicraft Electro Medicals (P) Ltd., Lucknow, India), was carried out to study antinociception. Each animal was placed in an acrylic tube and its tail was laid across a nichrome wire coil, which was heated by the passage of an electric current. The intensity of the current was kept at 5 mA. If necessary, small adjustments of the current were made at the beginning of the experiment in order to obtain three consecutive baseline tail-flick latencies (TFL) between 2.5 and 4.0 sec. All animals were screened for the tail-flick response. Only those showing a flick within 4 sec were included in the study. After drug treatment, if the animal did not respond to the stimulus, then three consecutive times (intervals of 5 min) within 10 sec, the tail was removed from the coil to prevent damage to the skin and it was considered as protected. In acute studies, animals were divided into 4 groups (vehicle control, 1, 3, 6 h prior) for each dose of losarton potassium (0.1, 1, 5, 30 and 100 mg/kg). Losartan potassium (Sun Pharma, India) was administered intraperitoneally (i.p.) in a constant volume of 1 ml/100 gm of body weight. For chronic studies, losartan potassium 0.04 and 0.4 mg/ml of stock solution was prepared in drinking water. Twenty ml of stock solution was supplied for 21 days, on a daily basis. It was observed that the average consumption of drinking water per day was around 12 ml/100 gm of body weight. The required dose of losartan potassium (3 and 30 mg/kg) was thus attained. After 1 h of final dosing, the mice were submitted to three TFL measures. In two other groups of mice (n=10) tail-flick latencies were also recorded 10 min after i.p. administration of the opioid antagonist naloxone (2 mg/kg) or saline. The data were analysed using the one-way analysis of variance (ANOVA), followed by post hoc comparisons between drug (treated at various time intervals) and vehicle treated control groups with Dunnett's test. P < 0.05 was considered statistically significant. Chronic treatment of losartan potassium (30 mg/kg, p.o.) for 21 days significantly delayed the onset of tail-flick to radiant heat in comparison with the vehicle, i.e., 7.36± 0.82 sec Vs. 3.60 ± 0.39 sec ( P < 0.01). This antinociceptive response of losartan potassium was reserved by pretreatment with naloxone [Table - 1]. In contrast, single dose of losartan potassium failed to show any antinociceptive effect (data not shown). Losartan provokes antinociceptive effects when ingested for a relatively long period of time, but with single dose treatment it does not show any such effect. This is in agreement with an earlier study done using the hot-plate test.[1] The present results also indicate that opioid antagonist naloxone can antagonise losartan potassium induced antinociception, suggesting that endogenous opioids may be involved in the modulation of this response.[3] Acknowledgments The authors wish to thank the Vice-Chancellor, Birla Institute of Technology and Science, Pilani, for providing facilities for this work.References
Copyright 2006 - Indian Journal of Pharmacology The following images related to this document are available:Photo images[ph06073t1.jpg] |
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