The bark of Terminalia arjuna L. (Combretaceae) has been widely used in Ayurvedic system of medicine for cardiac disorders since ancient times 123. Extensive reviews on various aspects of T. arjuna have been published 45. Both experimental and clinical studies showed the beneficial effects of the bark in congestive heart failure 678 and in ischemic heart disease 91011121314 and other cardiovascular complications 1516171819. The aqueous extract of T. arjuna showed contraction followed by relaxation on isolated rat thoracic aorta 1520. Results from our laboratory demonstrated that 70% alcoholic extract of T. arjuna reduced the platelet count on chronic treatment to dogs 21. Singh et al. reported that aqueous solution of 70% alcoholic bark extract of T. arjuna produced dose-dependent decrease in heart rate and blood pressure in dogs, though the mechanism was not determined 22. In the present investigation, a systematic study was performed to find the probable mechanism of hypotension produced by 70% alcoholic extract of T. arjuna in thiopental anaesthetized dogs.

The extract produced dose-dependent hypotension in the dose range of 5 to 15 mg/kg body weight while 20 mg/kg body weight doses was found to be fatal (Table 1). The hypotension produced by 6 mg/kg body weight was not blocked by prior administration of atropine (1 mg) or mepyramine maleate (20 µg) which blocked acetylchloine (8 µg) and histamine (8 µg) responses respectively. The hypotension of T. arjuna was blocked by propranolol (30 µg) which blocked the isoprenaline (10 µg) response. The responses observed with 6 mg/kg dose of the extract before and after administration of the antagonists are shown in Fig 1. The vehicle propylene glycol alone did not alter the blood pressure in the doses studied.

The hypotension produced by 6 mg/kg body weight dose of the extract was not blocked by atropine which could block the response of selected dose of acetylcholine indicating that the muscarinic mechanism was not involved. Studies with mepyramine maleate indicate that histaminergic mechanism was also not involved in the hypotension produced by the extract. Studies with propranolol which blocked the hypotensive response of the extract indicated that it may contain compounds having adrenergic ß-receptor agonist action. Even though propranolol is a non-specific ß-blocker, it is clear that the compounds present in the extract might be adrenergic ß₂-agonists, since adrenergic ß₂-receptor stimulation produces hypotension. Moreover, with the limitations of our study, one cannot completely ruled out the possibility that the observed hypotensive responsive could also be due to the effect of T. arjuna directly on the heart there by reducing the cardiac load. Earlier, it was reported that aqueous soluble fraction of 70% alcoholic extract (dried) of T. arjuna produced dose-dependent hypotension and decrease in heart rate 22 and were attributed to principles of the extract acting centrally. Our studies with 70% alcoholic extract dissolved in propylene glycol indicate the likely presence of compounds acting peripherally through adrenergic ß₂-receptor mechanism and/or by direct action on the cardiac muscle. Mallikarjuna and co-workers 20 studied the influence of aqueous extract of T. arjuna on isolated rat thoracic aorta and found contraction followed by relaxant effect. It was felt that the vasorelaxant effect of T. arjuna extract could contribute to the reported decrease in blood pressure in anaesthetized dogs as observed by Singh et al 22. The same experiment on isolated vascular smooth muscle lends support for our observation that the hypotension could be of peripheral origin. However, Mallikarjuna and co-workers indicated that the vasorelaxant effect of the extract was not blocked by propranolol. The possible reason for this variable effect could be due to the difference in the active principles present in different types of extracts used. This indicates that the 70% alcoholic extract might contain compounds to a higher degree whose activity was blocked by propranolol while the activity produced by the constituents of aqueous extract were not blocked by propranolol. Further investigations are needed on the isolates of Terminalia arjuna to study their cardiovascular effects in order to explain more in detail of the observed results.

The present results indicate that the 70% alcoholic extract of Terminalia arjuna produced hypotension of peripheral origin and support the claims of its traditional usage as cardiovascular medicine. The observed effect could be due to adrenergic ß₂-receptor agonistic and/or direct action on the heart. Detailed studies on the active constituents are needed which might provide new insights in cardiovascular drugs.