Baseline 3 Baseline 3 minute 5 minute 10 minute 20 minute 30 minute 40 minute 60 minute
5. INTRODUCTION
5.4 Cardiotonic effects of the phytochemicals and the triterpenoids
considering that the health care resources in this region are particularly scarce. Thus, the use of these triterpenoids for the treatment of hypertension would be proposed and encouraged since they share some similarities with thiazide diuretics.
Diuretics have also been reported to enhance the antihypertensive efficacy of multidrug regimens in addition to their being more affordable and achieving blood pressure control than other antihypertensive agents (Chobanian et al., 2003). This fact solidifies the assertion that the triterpenoids and some phytochemicals that have been shown to have diuretic effects should be used as adjuvant drugs to the western medicine as part of a multidrug therapy.
Atropine sulphate, a cholinergic receptor inhibitor, did not block the inotropic effects of the triterpenoids. Thus, it can be postulated that the observed positive inotropic effects of our triterpenoids were not mediated by muscarinic receptors. We can also speculate that the positive inotropic effects were not mediated indirectly via liberation of catecholamines.
This speculation is backed by the demonstration of the inotropic action in the reserpine- treated guinea pig atria. However, the positive inotropic effects of the triterpenoids were blocked by a ~-adrenergic blocker, propranolol. This inhibition demonstrates that the positive inotropic effects of the triterpenoids were mediated through ~-adrenergic receptors.
The experiments of the cardiotonic effect of isoprenaline after pre-treatment with the triterpenoids showed that OA, UV and UA had a potentiating effect on isoprenaline. The action was not additive since the effect of isoprenaline on the background of the triterpenoids was more than the maximum effect observed with isoprenaline alone. The study did not ascertain as through which mechanism the potentiating effect was done. We can only speculate on a number of possibilities that the potentiation might have come about. Firstly, the binding of triterpenoids to the ~-receptors might have caused a conformational change (allosteric modifications) to the adenylate cyclase complex that enhances the activity of isoprenaline. This mechanism has been shown to happen in brain tissues whereby pre-treatment of the tissues with forskolin potentiated the effect of hormones (Seamon, et al., 1984). The second possibility is that the triterpenoids in addition to their acting through the receptors might also be working downstream to the receptors. In this case, the triterpenoids might have cause an increase in the free Ca2+ concentration. The increase would be either through the inhibition of phosphodiesterase or through an increase in the release of Ca2+ from Ca2+ stores like the sarcoplasmic reticulum.
The last possibility is that the triterpenoids might have increased the sensitivity of the contractile apparatus for Ca2+. This mechanism has been shown to be displayed by the n-
butanolic fraction from Berberis aristata fruit (Gilani et al., 1999).
Of all the plants screened, only Plantago lanceolata and Prunus africana displayed a positive inotropic action. A Medline search demonstrated that this is the first time that a positive inotropic effect of these plants has been reported. This inotropic effect was also blocked by a ~-adrenoceptor blocker, propranolol, indicating that the effect was mediated through the ~-adrenergic receptors. What was more intriguing was that these plants did not yield the highest percentage of triterpenoids in comparison to the other screened plants.
This seem to suggest that the positive inotropic action of the two plants might be due to a synergistic effect of the triterpenoids and some other yet to be identified compound. It also showed that, for therapeutic purposes, a crude extract of the whole plant leaves might have better effects.
A number of the plants screened displayed a dose-dependant biphasic inotropic effect. The plants that had this effect are Plantago major, Psychotria serpens, Buddleja salvii/olia, Centella asiatica, Tetradenia riparia and Clerodendrum trichotomum. These plants had a positive inotropic effect at one concentration and a negative inotropic effect at another concentration. This is not the first time that this kind of action has been reported since other studies of plant extracts have also shown it. For instance, Pennacchio, et al., (1995) showed that Eremophila alternifolia extracts displayed a biphasic inotropic effect. This biphasic was not mediated by neither a-adrenergic nor ~-adrenergic receptors.
The study also showed that some of the screened plants have a negative inotropic effect on a guinea pig atria. The plants that had this action are Syzygium cordatum, Eugenia jamboiana, Combretum moile, Terminalia sericea, and all the four Psidium guajava subspecies. The mechanism of action was not demonstrated in this study. However, in case of the guavas, the negative inotropic effect was probably mediated through the cholinergic receptors. Conde Garcia et ai., (2003) have recently shown that the negative inotropic effect of guavas is not blocked by propranolol nor naloxone but by atropine sulphate. Thus, the negative inotropic effect did not involve ~-adrenergic receptors nor opiod membrane receptors but rather through cholinergic receptors. The authors assert that the guavas mostly probably inhibited Ca2+ inward currents thereby causing a negative inotropic effect. These negative inotropic agents might have the potential of being used in the treatment of hypertrophic cardiomyopathy whereby they can improve cardiovascular hemodynamics. They also point to their potential use as antiarrhythmic agents.