African Journal of Biomedical Research, Vol. 8, No. 1, 2005, pp.59-61
Inhibitory Effects of Musanga cecropioides on Noradrenaline and Potassium-Induced Contractions in Rat Thoracic Aorta
PETER I. AZIBA
Department of Pharmacology & Therapeutics, College of Health Sciences,
Olabisi Onabanjo University, Ago-Iwoye.
Accepted: October, 2004
Code Number: md05010
The pharmacological effects of Musanga cecropioides on rat thoracic aorta were examined in high K+ medium (55mM), Ca2+ 3mM) induced vasoconstriction was inhibited by Musanga cecropioides in a concentration-dependent manner. The tonic contractions elicited by KCI 55mM were relaxed by Musanga and were more marked in 0.45mM Ca2+ than 1.8mM Ca2+ medium. NA -induced responses were antagonized non competitively by Musanga. NA- sustained contraction was relaxed, the relaxing effect of Musanga was not antagonized by indomethacin or methylene blue. It is concluded that Musanga relaxation of the rat aorta does not involve cyclo-oxygenase, nor cAMP pathway, but unique, unlike those of known classical vasodilators.Keywords: Musanga cecropioides, contraction, inhibition, Potassium, thoracic aorta
Medicinal plants have been used as traditional remedies in Africa. In our previous studies, we reported that Musanga cecropioides didnot affect ach-induced contractile response but produced significant inhibition of the movement of the rat and rabbit gut smooth muscles, Aziba et al (2000). It is also reported to have a blood pressure lowerhig effect and it is used to procure painless childbirth, Adjanohoun et al (1989). These actio prompted us to investigate in the present study, the effects of the aqueous extract of th leaves on the rat aorta on contractions induced NA an K on receptor and voltage mediated responses respectively.
MATERIALS AND METHODS
Male Wistar rats(200-350g) were killed by a blow on the head. The thoracic aorta was located, while excess fat and connective tissue was removed. The vessels were cut into strips according to Furchgott and Bhadrakom (1953). The contractile responses were rc r:d isometrically using a force displacement transducer(FT-03,Grass) and the signals amplified with a polygraph (Grass, model 7D).the preparations were equilibrated for 1hr in the organ bath containing 10ml modified Krebs solution of the following composition (mM): NaCI 118, KCI 1.2, CaC12 1.8, MgCl2 1.2, KH2PO4 1.2, NaHCO3 25,and glucose 11 .7.the tissue bath solution was bubbled with a 95% 02,-5% CO2 gas mixture which maintained the solution at pH of between 7.2-7.4. in some preparation, K Krebs solution was prepared by replacing NaC1 with KCI. The kreb solution with high potassium concentration was prepared by mixing the K krebs. The calcium free krebs solution was prepared by deleting Ca2duñng preparation of the Krebs solution. Drugs used were Noradrenaline hydrochloride (Sigma,St. Louis,MO USA) methylene blue (laboratory I-IBL reagent.
The adult albino rat(>6 weeks old,Sprague Dawley strain) used in the experiment were supplied by the National institute of Medical Research, Yaba, Lagos, Nigeria. The animals were maintained in the Preclinical House in a well ventilated condition, under constant temperature (30°C) and humidity 50% and exposed to 12hr light- dark cycle for 2 weeks before use. The animals were fed on standard livestock pellets (Pfizer, Nigeria Ltd), with free access to water and were treated ethically according to the guidelines for the treatment of experimental animal as determined by the animal council.
The data obtained from this experiment were expressed as the mean (S.E.M) for nobservation. The value obtained in different groups were compared using test and probabilities of less than 5% (P<0.05) were considered to indicate a significant difference.
Effect of M. Cecropioides on K+ Induced Contractions
In high K+ (55mM) Ca2+ free medium. The cumulative addition of Ca2+ >3mM to the aortic strip caused increase in contractile force. The maximum contraction>3mM was 1.2 +_0.25g (n = 10). After incubating the strip in musanga (10 -1000mg/mI) for 10 minutes, inhibited contraction in a concentration dependent manner (fig. 1A), the IC50 value was calculated to be 1 5.increasing the incubation time did not cause any pronounced inhibitory action of Musanga. (fig. 1B) low doses inhibited the high K+ induced Ca2+ dependent contraction, suggesting action on voltage operated Ca2+ channel effect.
Effects of Musanga on Noradrenaline Induced Contraction
Cumulative addition of NA (5nM - 2nM), caused increase of contractions of rat aorta. The maximum contraction induced by 10nM noradrenaline was 1.56 ± 0.12g (n = 10). Musanga produced a non competitive blockade of noradrenaline induced contraction. This relaxing action of Musanga was not blocked by either methylene blue 40nM or indomethacin 10nM. Pre-incubated aorta in Nifedipine for 10 minutes, K+ 55mM induced contraction was completely blocked while it had no effect on NA- induced contractions (Fig 2).
Rat aorta pre-treated with Musanga cecropiodes in this study inhibited contractile responses to Noradrenaline and high Ca2+ 55mM), it also caused the relaxation of the blood vessel when Musanga was added to NA- induced sustained contractions. Contraction of Vascular smooth muscle requires increase in free cytosolic Ca2+ (Karaki and Weis 1 979),the actions of Musanga was more enhanced in low medium Ca2 0.45mM, then high Ca2+ medium 1.8mM in this study. The K+ induced contraction of the smooth muscle arise from increased Ca2+ influx through voltage dependent Ca2+ channels (Karaki and Weis 1979). Bay K 8044, a derivative of Nifedepine, a known Ca2 entry facilitator did affect this action of Musanga. The inhibitory effect of musanga was much reduced in high Ca2+ medium 1.8mM. .The tonic tension in response to Noradrenaline results from Ca2 entry through receptor operated calcium channel (Bolton 1979). The inability of musanga to inhibit the actions of indomethacin and methyIene blue, rules out, the possibility of the plant action involving cyclo-oxygenasse nor cyciic AMP pathways. The totality of this result indicated that the inhibitory effects of Musanga cecropioides on the contractile responses caused by high K+ or NA- are not due to increase in cyclic nucleotide. Yang- Chong et al (1993) Musanga relaxes the rat aorta in a unique manner different from the known vasodilators and its actions on receptor is not specific since on receptor mediated responses, it suppressed maximum contractile response induced by Noradrenaline and high K+ in a non competitive manner.
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