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Indian Journal of Pharmacology, Vol. 36, No. 6, November-December, 2004, pp. 381-382 Research Letter Antihypertensive effect of newly synthesized acyl amino substituted propanolamine derivatives, DPJ 890 and DPJ 955 in rats Nandakumar K, Singh R, Bansal SK, Bodhankar SL, Jindal DP, Coumar MS, Bhardwaj SH Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune - 411 038 Code Number: ph04134 Sir, Hypertension described as a ′silent killer′ increases the incidence of cardiovascular diseases. b blockers have been widely used since more than four decades for the treatment of hypertension. However these drugs are contraindicated in asthmatics and diabetics.[1] In order to improve the therapeutic variety, Late D. P. Jindal (Panjab University) had synthesized new compounds for b blocking activity. The synthesis and adrenoreceptor ( b1 and b2) binding affinities of these compounds were reported earlier.[2] Previous work indicated that DPJ 890 and DPJ 955 possessed greater b1 adrenoreceptor selectivity than standard b blocking drugs like atenolol and propranolol among various compounds synthesized from the series. As a collaborative research work we received compound DPJ 890 and DPJ 955, which are chemically N[4 - (3 - tert - butylamino - 2 - hydroxy - propoxy) - phenyl] - 3,4 - dimethoxy benzamide oxalate and N[5 - (3 - tert - butylamino - 2 - hydroxy - propoxy) - naphthalene-1-yl] - acetamide oxalate respectively for evaluating the antihypertensive potential. Female Wistar rats (175-200 g) purchased from the National Toxicology Centre, Pune, India, were housed in a clean environment, at a temperature of 25±1 °C and a relative humidity of 45 to 55%, under 12/12 h light/dark cycle. The animals had free access to food pellets (Chakan Oil Mills, Pune, India). The research protocol was approved by the Institutional Animal Ethics Committee (IAEC) of the Poona College of Pharmacy, Pune, India. Two-kidney 1 clip model of kidney ligation was used to produce hypertension in rats. Group I animals had not undergone renal ligation. Rats were anesthetized with urethane (1.25 mg/kg, i.p.) and the left renal artery (LRA) was ligated[3] except in Group I rats. After renal ligation the animals were housed and provided with 1% sodium chloride solution instead of water. After 6 weeks of LRA ligation the animals were divided into 9 groups consisting of 6 animals in each group. Group II received vehicle [saline (0.9% sodium chloride in water), 1 ml/kg, i.p.], which served as LRA ligated control. Groups III, IV, V, VI, VII and VIII received a dose of DPJ 955 (3, 10 or 30 mg/kg) or DPJ 890 (1, 3 or 10 mg/kg) intraperitoneally, respectively. Groups IX and X received standard drug propranolol (30 mg/kg, i.p.) and atenolol (10 mg/kg, i.p.) respectively. Saline or drug treatment was initiated after 6 weeks of LRA ligation and treatment was continued for 7 days. The mean arterial pressure (MAP) was recorded by directly cannulating the carotid artery using four-channel physiological data acquisition system (MP 30, BIOPAC Systems, Inc., Santa Barbara, CA). MAP was recorded at the end of the 7th week, 1 h after the administration of the last dose of saline or test drugs. The heart rate was computed from the ECG recording. The statistical significance of the difference between means was determined using one-way analysis of variance followed by Tukey test. P<0.05 was considered significant. LRA ligation after 7 weeks had significantly (P<0.01) increased the MAP compared to non-ligated rats. However, the heart rate was not significantly changed as compared to non-ligated rats. Treatment with DPJ 890 (1, 3 and 10 mg/kg, i.p.) and DPJ 955 (3, 10 and 30 mg/kg, i.p.) produced a significant, dose dependent decrease in the MAP and heart rate of LRA ligated rats. Significant reduction in MAP and heart rate was observed in hypertensive rats treated with propranolol (30 mg/kg), atenolol (10 mg/kg), DPJ 890 (3 and 10 mg/kg) and DPJ 955 (10 and 30 mg/kg). The fall in the the MAP produced by DPJ 890 (10 mg/kg) was greater compared to atenolol and propranolol while the effect of DPJ 955 was less than that of atenolol but greater than that of propranolol [Table - 1]. The observed change in the MAP and heart rate in LRA ligated rats with DPJ 890 may be due to its stronger receptor (b1) binding property compared to atenolol. ACKNOWLEDGEMENTS The authors would like to thank Dr. R. Balaraman, Professor, Department of Pharmacology, G. S. Patel Postgraduate Center for Pharmaceutical Education and Research, Vadodara, India for his valuable suggestions. The authors are thankful to The Principal, Dr. S. S. Kadam and Vice Principal, Dr. K. R. Mahadik of the Poona College of Pharmacy, for their encouragement and support. REFERENCES
Copyright 2004 - Indian Journal of Pharmacology The following images related to this document are available:Photo images[ph04134t1.jpg] |
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