Hypotensive and other pharmacological properties of tetrapleura tetraptera (fam. mimosaceae)

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Tetrapleura tetraptera has many traditional medicinal uses, mainly in the management of convulsions, leprosy hypertension inflammation and rheumatic pains. The hypotensive effect of T. tetraptera was studied on anaesthetized rats, cats and rabbits. T. tetraptera exhibited concentration-dependent decrease m the mean arterial blood pressure in experimental animals. The hypotensive effect was found not to be species specific. Maximum reduction of mean arterial blood pressure for 5 mg/kg of T. tetraptera was 34.70 ± 7.50 mmHg in rats. The hypotensive effect of T. tetraptera (5 mg/kg) was not inhibited to any significant level by mepyramine (0.5 mg/kg), atropine (1 mg/kg) and propranolol (0.5 mg/kg) as compared to their respective specific agonists. Cardiovascular studies carried out on intact and isolated frog heart, isolated perfused rabbit heart and isolated guinea-pig atria showed that T. tetraptera caused a dose-dependent bradycardia and negative inotropism that were not inhibited by atropine. Experiments were then performed to ascertain if K contributed to the responses in frog heart preparations. The extract (5 mg/mi) and K+ (0.06 mg/mi) were administered separately and the effects compared on both the heart rate and contractile force. The significant difference (P < 0.001) between the changes produced suggested that the heart rate and contractility cannot be attributed to its K+ content. T. tetraptera at 0.5 mg/nil inhibited the maximum calcium-induced contractile force by 56% and the heart rate by 37% of isolated guinea-pig atria. T. tetraptera did not affect KCI- and noradrenalineinduced contractions but caused non-ompedtive inhibition of the CaCI2-induced concentration- response curves of the rabbit aortic strip. Experiments on isolated guinea-pig ileum and rabbit jejunum showed that T. tetraptera had cholinomimetic activity which was specific on these smooth muscles and was probably mediated through muscarinic M3-receptor subtype. Competitive antagonism was established between the extract and atropine on the guinea-pig ileum. T. tetraptera was very stable to the effect of cholinesterase. The extract produced concentration-related relaxation of rat anococcygeus muscle, rat uterus and guinea-pig taenia coli, Cumulative addition of T. tetraptera (0.1 — 100 mg/mi) produced ‘biphasic’ effects on isolated rat anococcygeus, rabbit jejunum and isolated rat uterus preparations. The extract antagonized the effect of a number of agonists on various smooth muscle preparations (non-specific inhibitory effect). The non-specific inhibitory effect of T. tetraptera was further established on the anococcygeus in that the contractile effects of noradrenaline, carbachol, Ca2+ and K+ were suppressed noncompetitively. The calcium antagonizing actions of T. tetraptera and nifedipine were examined in partially depolarised left atria, depolarized rabbit vascular tissue and guinea-pig isolated taenia coli preparations. These compounds produced not only a concentration-related displacement of the concentration-response curve for CaC12 to the right, but also a depression of the maximum response to CaCl2. This showed that interaction between the compounds and calcium is not competitive. The calcium antagonizing property of T. tetraptera is much weaker than that of nifedipine in potency. No acute toxic symptoms were observed after oral doses up to 0.80 g/kg in mice and oral doses up to 3.20 g/kg in rats. Sub-acute toxicity studies revealed no damage to the vital organs studied. T. tetraptera was found to cause pronounced increases in the weights of rats. No histological abnormalities were observed in the liver, kidney, heart, spleen, lung and intestine. There was negative correlation between the dose of T. tetraptera and the duration of pentobarbitone-induced sleeping time.
A thesis submitted to the Department of Pharmacology in fulfilment of the requirements for the degree of Master of Philosophy, 2005