RESEARCH PROJECT TOPIC ON THE EFFECT OF COLA NITIDA AND GASINIA COLA ON RABBIT BLOOD PRESSURE.
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ABSTRACT
The effect of Cola Nitida and Garsinia kola extracts on Rabbit blood pressure in 12 rabbits has been studied. A wide concentration of 10mg/ml to 500mg/ml of solutions of crude (aqueous) extracts of both Cola Nitida and Garsinia Kola was used.
Infusion of the concentration range of 10mg/ml to 500mg/ml of cola nitida caused an initial dose-dependent increase in blood pressure up to the concentration of 250mg/ml then the follow up infusions of 250ml/ml and 500mg/ml caused a marked dose-dependent fall in blood pressure whereas with infusion of the same concentration of Garsinia kola caused initially no change in blood pressure up to the concentration of 80mg/ml. but starting with the infusion of 80mg/ml of extract solution up to 500mg caused a dose dependent fall in blood pressure.
CHAPTER ONE
INTRODUCTION
The kola ‘’nut’’ chewed habitually by millions in Northern Nigeria, is one of 8-10, 2.5 to 5cm long, red or white fleshly seeds in a large oblong fruit produced perennially by a large tree (genus, cola: Family, sterculiacca). It is indigenous to the tropical rain forests of West Africa, West Indies, Brazil and java. Apparently some effects on chewing the odourless nut with a astringent taste has enhanced its continued use for a near 1000 years in Northern Nigeria. The habit, if not comparable certainly shows similarity to the ‘Betel’ nut chewing of Asiatic communities. It is used in social intercourse, a must in welcoming a quest, a prelude to conversation, or a concluding event to an agreement, in fact, by symbolism a language by itself, even assisting the traditional diviner to ascertain the divine acceptance of a sacrificial offering. Its role in West African society as not entirely socio-religious. The collar chocolate and the lacquer and laxatives of which it has become an important ingredient. Production in Nigeria has steadily increased since the turn of the century, rising from 7000 tons in 1930 to 1000.000 tons in 1955 (Hansen, 1964). It would be hazardous to guess how much of this is chewed in Northern Nigeria, but rapid and easy transport has ensured ready availability at low cost, and kola nut chewing has natured from an established custom to an increasing daily habit.
The Arabs must have been convinced of its ability to stave off hunger and allay thirst when the bartered gold dust for kola, weight for weight, before they made the arduous trip across the sahara. It is a far cry from the physical rigor of a desert journey to the mental stress of a sedentary desk worker, but again kola is apparently helpful. The popular new is that while abolish hunger to the mental stress of as sedentary desk workers, but again kola is apparently helpful. The popular new is that while abolish hunger it enables the user to stay alert and make strenuous physical effort whiteout undue fatigue. Daniel in Sierra Leone in 1864 first identified alkaloids in kola-nut similar to those in tea and coffee and since then the effects have been attributed singly or collectively to caffeine, kolatin (Tanin), theobrowine and betaine. The kolain – caffeine-glucose complex is thought to be the active ingredient and chevalier and perrot (1911) summarised the observations of Barr (1894) – ‘that small closes caused mental fatigue and heavy sleep. It was also though to act as a general stimulant of the digestive system heart and blood pressure, causing heart failure in excess. Since Barr’s observations on the physiological effects of the nut, a large void exists in the literature except that the British pharmaceutical codex and the United States National formulary record its medicinal sue as a tonic stimulant and a diuretic.
GASINIA KOLA HECREL
In South Nigeria, the Rorubas call it orogbo, Benin, eduni Ibo, adii – Onitsha, adu and Ugolu; Aro-chuwku-inu, Owerriaku inu, akuruma, Awka-agugolu; Ijaw akan; Efik-ofiari.
If exists commonly in moist conditions, often in association with cola nitida or cola acuminate, and found up to an deviation of 3, 000ft. it is planted near villages in lower Dahomey and Lagos colony.
The seeds are the important product, anda are seen in markets from Senega (obtained from Sierra Leone) to south Nigeria and to parts of the interior (from Lagos etc.). They do not separate into two cofyledons. They have in chewing a bitter, astringent and resinous taste, somewhat resembling that of the raw coffee bean, followed a slight sweetness, and are appreciated rather as an adjuvant than a substitute for true kola, increasing the user’s enjoyment of the latter and allowing of the consumption of larger quantities without indisposition. Similarly they enhance the flavour of native liquor. The residue after chewing is white. They are eaten raw and not in prepared food. Medicinally they are sad to prevent or relieve colic, and particularly to be curative for colds in the head or chest, relieving cough and hoarseness and improving the singing voice. In Lagos, they are considered effective for bronchitis and throat troubles. Pounded and mixed they are taken also for headaches and for dysentery. They are recorded also as an antidote to the poison of strophantas gratus and until recently it’s been demonstrate to have antihepatotoxic effect as well as some caridvascular effects. The active principle is probably contained in the resins found in the seed, no caffeine or other alkaloid being found in the seed, no caffeine or other alkaloid being found on analysis the fruit itself is edible.
The root is a bitter other stick, sold in the form of small bundles in native markets, chiefly in the forest region. In Sierra Leone, the bark is said to be added to palm wine to increase the intoxicating effort. A similar use is recorded in Gabon with regard to the bark of an allied species, G Klainei pierre. The sap is applied to cure parasitic skin diseases. According to conraum the yellow resinous sap of the tree is used by some Cameroonian tribes to protest from rain, the power in the priming pans of their guns; also the twigs burn lightly, and can be used as tapers.
The wood is yellow with a brownish centre, hard, chose grained, finishing smoothly and taking a good polish and probably durable; it has been used locally in Nigeria.
(the useful plants of wesh tropical Africa) dalziel 1937. A. Biffavanones with c – 3. 8N- linkages are the major metabolites occurring in the genus Gareinia (family Guttiferae). Garcinia species are employed in traditional medicine for the treatment of various diseases, including hepatitis, laryngitis and mouth infections (Iwu and Igboko, 1982). Co-occuring with th4 biflavanoness are xamth ones and bezophenones.
The inflavancids of Garcinia can be divided into two sub groups, those made up of two flavanone units and those that consist of one flavone and one falvenone sub-unit. The biflavaones are the most dominant components in most Garcinia speices (waterman and Hussain, 1983).
Pharmacological activities of Garcinia biflacanones include anti-inflammatory, antihepatotoxic, anticholesteremic, etc.
The Garcinia biflacariods inhibits the growth of gram positive and gram negative micro- organisams both invitro and in vivo. In bacteria test system, the activity was found to be bacteriocidal and gastrointestinal conjugation of the isolates did not diminish this effect.
The biflavanones of Garcinia are pharmacolinetic advantages over simple monomeric flavoroids; for example, the biflavanoids.
Unfortunately when I travelled to Nsukka to see professor. M.M Iwu of the pharmacognosy department in University of Nigeria, Nsukka who himself has worked on several parameter with the Garcinia kola, he confirmed to me that the work on the effect on Garcinia lola, he confirmed to that the work on the effecto Gracinia kola, he confirmed to me that the work on the effect of Garicnia kola, he confirmed to me that the work on the effect of Garcinia kola on the cardiovascular system has just started and that no conclusion had been made yet.
BLOOD PRESSURE
Blood pressure is defined as the force needed to push blood through the vessels of the body and it depends on cardiac activity. This parameter is affected by the administration of certain exogenous substances into the circulatiton. Such as the case with Hausa Kolanut extract as well as Bitter Kolanut extract.
There are variations between the pressure in different blood vessels. This was first appreciated by a medieval artist, Giovanni di pado (1403 – 1483) who painted the hedeading of folin the Baptist. In this painting, he illustrated three streams of blood from a severed neck; one dripping and two spurting. From our acknowledgement today, it is evident that the spurting occurred indartories and the dripping in a vein.
The blood pressure in any vessel reflects an interplay between flow and the resistance to that flow. The factors which influences these two parameters are intricately interwoven with the structure of the components of the cardiovascular system.
Literature reveals that a lot of work has been done on these factors which include heart rate, cardiac contraction, vascular musculature, etc.
The activity of these factors are further modulated by nervous, volume and humeral mechanisms. These mechanisms also influence the blood pressure directly (Guyton 1981).
In order to determine the value of blood pressure, various method have been device; direct and indirect. The direct method as invasive while the indirect is not.
The first blood pressure measurement was done in the eighteenth century (Stephen Hales 1733). He measured the blood pressure of a mare by inserting a brasses tube blood rose in the tube. A lot of improvement have been made on this, such as the administration of annosthesia to reduce the pain experienced by the use of a mercury manometer, (poiseulle 1828). Which made it feasible to measure blood pressure indoors. Carl Ludwig added a float to pensueulle’s manometer making it possible to obtain a continuous according of blood pressure on a homograph.
Remarkable improvement have been made in these methods. For as electro-optical, inductive mechano-electronic tube, and-guage, the procedure employed in this investigation was first devised by London (1951) and modified by Labi (1972).
In this method pressure was recorded from the caro artery. The artery was vanullated and the canulla was to physiography via a tube filled with heparinised saline. In Tubi’s method, a fluid filled ammeter making it possible to obtain a continuous latter has several advantage. One of which is the fact that systolic and diastolic pressure are recorded. This is in contrast to the former which records only the man arterial pressure (MAP),.
Since the major objective of this experiment to extrapolate to result human we must not fail to mention how important blood pressure is to humans we must not fail to mention how important blood pressure is to human beings. It is important to be controlled at nor mal level because an increase or decrease from the central level can be harzadons to human health. It is commonly accepted that the normal human B.F is a mean of about 120/80, but there are wide variations from these. Which still come within the normal range which depends on age eg world health organisation (WHO) defines Norm tension in Young adults, below the age of 40 as 140/90 Hypertension for such age group will not normally be described until they have attained the level of 145/95. Hypertension is a chronic debility disease so human efforts genre towards maintaining a normal blood pressure is an important physiological phenomenon. Conversely Hypotension or reduction in Blood pressure can be equally a serious condition. The case of reduced blood pressure is even more disastrous in that it does not allow for a chronic state to arise. For example, a sudden reduction in blood pressure can result in fainting, shock, and death if not abated on time. It is therefore of paramount importance that normal blood pressure should be maintained in man. The problem of maintaining normal blood pressure in man is a herculean task. This difficulty is compounded by the fact that man is an erect posture increases the task and the need for maintenance of a normal blood pressure.
There are various factors responsible for the control of normal blood pressure in man. These factors include:
1. Pumping action of the Heart
2. Peripheral resistance
3. Quantity of blood in arterial system
4. Viscosity of blood
5. Elasticity of the vascular wall
6. Central Nervous system effect
7. Autonomic Nervous system effect
8. Receptor factors
9. Endocrine factors
10. Chemical or ionic effects
11. Viscometer centre activity
12. Kidney effect
13. others
(1) PUMPING ACTION OF THE HEART:
The pumping action of the heart is important for the maintenance of blood pressure. When the Heart fails normal blood pressure cannot be maintained because the pump is inefficient. It is known from Haemodynamic principle that Co = Sv x HR. the cardiac output by itself affects the blood pressure because the pressure in the arterial system depends on the quantity of blood that the heart can pump.
If there is less pumped out by the heart there will be Hypotension and if there is a great deal pumped out by the Heart, there will be Hypertension. This is because the haemodynamic equation says that
Q = Ap
A where Q = quantity of blood in circulation.
P = pressure difference at 2 ends of the tube
R = peripheral Resistance.
Blood pressure = Q x R
Since the blood flow from the heart is tantamount to cardiac output (co) and cardiac output is related to stroke volume (SV) and heart rate (HR) indirect proportionality. Ti implies that whatever effects the stroke volume or Heart rate will affect. Cardiac output (co) and consequently affect the blood pressure. In certain diseased conditions like myocardial impaction. The heart muscle is diseased and weakened in its activity therefore the stroke volume will be diminished. This will adversely affect the blood pressure. In other conditions such as sinoatrial node (SA node) and Atrioventicular node (AV node) blockade or bundle branch blockade. Heart rate may be affected leading to cardiac output and blood pressure reduction.
(2) PERIPHERAL RESISTANCE:
Peripheral resistance is dependent upon the internal diameter (calibre) of the small vessels especially the arteries and, to a less extend, of the capillaries and upon the viscosity of blood. Haddy demonstrated the significant role played by smaller arteries and veins in contributing to resistance across systemic vascular beds. In fact, the minute vessels of the muscles and of abdominal structures are known to constitute the greater part of peripheral resistance.
Peripheral resistance has been defined by various terminologies. Green has used a unit of peripheral resistance (PRU) as equal to 1mmHg/1ml/min. many authors take such a artic and by expressing pressure in dynes per square centimetre and flow as millimetres per second. The peripheral resistance can be given absolute units of force peripheral resistance ® = mean blood pressure (mmHg) x 1.332
Cardiac flow (ml/sec.)
R = dynes/cm2 = DYNES SEC
Cm3/sec CM5
= synwa,sec
Cm5
1.332 is used to convert pressure to dynes. Studies show that peripheral resistance calculated this way varies inversely with the size of animal, directly with the surface area.
It is now customary to divide blood vessels into a series of segments that afe defined by function (Folklow; 1966).
WINDKESSEL VESSEL: These convert the rhythmic outflow of the heart to a fairly smooth flow in the flow in the peripheral arteries. These vessels include the aorta and its large branches.
RESISTANCE VESSELS: These include chiefly the small arteries the arterioles and to a lesser extend capillaries and the smallest venues. They determine the resistance to the forward flow for blood by virtue of the sphineteric action.
Factors which influence them include myogenic tone. Locally generated metabolites. Local and circulating hormones and the sympathetic nervous system. The capillaries form a group known as exchange vessels. The next group which consists of limited segment of precapillary arterioles are the sphincter vessels. Then contraction may shut off the distal capillaries.
There are, also the capillary vessels (mainly veins). Whose changes in diameter have a propanety vessels (mainly veins). Whose changes in diameter have a pronounced effect on the filing of the heart and thus on cariac output.
Poiseuille’s equation shows that blood pressure depends on carida output, peripheral resistance and blood viscosity.
The latter depends on the corpuscular content of blood which shows only minor variations during the course of the day. Therefore its variations in the product of cardiac output and peripheral resistances that determine the blood pressure.
Factors that influence the peripheral resistance:
New Nervous
The complex structure of the vascular system calls for artificial simplification in an attempt to understand the factors which influence the peripheral resistance. Poiseuille’s formula states that ‘’pressure varies directly as the length of the tube indirectly as the fourth power of the radius. The vascular system is branched, elastic and highly reactive and the viscosity subject to the peculiarities related to the presence of cells therefore penseuille’s law cannot be applied quantitatively to this system.
These non-nervous factors serve as a foundation upon which neurogenic mechanisms act to determine the magnitude of peripheral resistance. Investigations including acute experiments suggest that the peripheral resistance largely depends upon the flow of sympathetic impulses to blood vessels. The work NODOWELL has shown that carbon dioxide acts locally as a vasodilator peripherally but centrally stimulates the vasoconstrictor canter in the medullar causing vasoconstriction.
Catecholamines increase myocardial contractility, heart rate, haemoglobin concentration, haematocrit, coronary blood flow, total oxygen consumption and myocardial oxygen consumption. In this way, they influence peripheral resistance hence blood pressure.
3. THE QUANTITY OF BLOOD IN THE ARTERIAL TREE
The quantity of blood in the arterial system is important for control of blood pressure because of there is not enough in the system, there won’t be enough to be pumped out during cardiac output phase, and this will adversely affect blood pressure by reducing it. So in a case such as haemorrhage the quantity of blood in the circulation is considerably reduced and so there is a fall in blood pressure. If this fall in blood pressure continues unaltered it can lead to syncope and shock and even death.
VISCOSITY OF THE BLOOD
Viscosity refers to the ‘’thickness’’ of any liquid. When viscosity increases the pressure required to force the fluid along the length of a narrow tube in a given time, increase is constant, it will take a longer time for the liquid to transverse the tube. The frictional resistance developed between the parts of the liquid is greater when the viscosity is high compared to when it is low since it depends upon the degree to which the molecules within the fluid can cohere.
Blood is about five time more viscous than water. Various observes have obtained values between 4.5 and 5.5 for the viscosity of blood taking distilled water as unity.
How the viscosity influences blood pressure is again a matter of outflows. Where they during force and calibze of the vessels remain unchanged, the frictional resistance developed in the region depends on the viscosity. Therefore increase in the number of cells in the blood will culminate increase in the peripheral resistance which will invariably lead to an increase in blood pressure. However increase in viscosity rarely occurs in normal cases or in experimental conditions during blood pressure measurement.
LELASTICITY OF THE VESSEL WALLS
This factor alone determines the radius and thence the diameter of the vessel and since the radius has a profound effect in the blood flow it hence affects the blood pressure.
To control the blood pressure therefore adequate control of the elasticity of the vessel wall is important. The elasticity of vessel wall is in the Tunica media and is predominantly controlled by sympathetic innervation which can cause vasoconstriction when stimulated. Below 30 – 40mmHg, the elasticity of the belles wall is not of much importance because such low pressures can no longer stretch the vessel wall due to the phenomenon of critical closing pressure (CCP).
When the vessel wall loses its elasticity as in old age, relative Hypertension develops.
CNS EFFECT
There is an anatomical organisation of the central Nervous system to the control of the heart and blood vessels. Transaction of the spinal card at any cervical level results in an immediate and profound fall in arterial pressure (claude Bernard; 1863). Central stimulation of a nerve such as the sciatic cause’s depression of the pressure reflexes (Owsjannikor 1871). It has been longest known that there is a cerebral mechanism that influences the circulatory system at the bulbar or medullary level termed the vasomotor centre of the medullar oblongata. This centre was discovered in ludwig’s laboratory in 1870.
Another groups of workers have concluded that the centre for vasoconstriction is located somewhere in the bulbar region. Within the hypothalamus are excitable elements that have conductive continuity with the cardiovascular innervations (karplus and Kreidl 1909). In this work, changes in heart rate and blood pressure were observed following ablation and stimulation using electrodes. The hypothalamic level rather then medullar is the basic mechanism for the maintenance of blood pressure (keller 1960). In the same year (1960) oberholzer trying to locate circulatory centres in the medullar and midbrain found that ablation experiments led to the concept of a vasomotor centre while later electrical stimulation led to the assumption of substres which dominate the spinal vasomotor outflow consist of a medially located ‘’depressor’’ zone and crandin lateral ‘’pressor’’ zone. The depressor zone is considered to relay baro-receptor influences while the pressor zone is the autonomous centre for the maintenance of a general vasomotor tone.
Vasomotor fibres are traceable in either the pyramidal tract or scattered in the lateral reticular formation at the medullary level. From here. They descend into the ventral parts of the lateral column.
Study of the reactivity of the circulatory system to presser drugs provide some relevant information of the amount, of sympathetic discharge to the heart and blood vessels (Smirk, 1970) even though there is no satisfactory way of separate determination.
ANS EFFECT
The hypothalamic control of the sympathetic outflow to blood pressure control is more important than the medullary sympathetic controls. The hypothetic controls may occur as part of the limbic pressure during emotion. When there is a mild to moderate stimulation of the limbic system of the sympathetic outflow to the control of blood pressure causing an increased blood pressure.
If however, there is severe stimulation of the limbic system, the parasympathetic outflow dominate and this is the physiological basis for fainting and even shock when an exceptionally emotionally predisposed individual gets a very bad or sometimes a very good news.
RECEPTORS
There are numerous receptors that control the blood pressure. They modify it in various forms. Receptors such as Baroreceptors and chemoreceptors affect the blood pressure through the vasomotor centre but other receptors such as pains receptors can also affect the blood pressure eg. Moderate stimulation of pain receptors can lead to increase in blood pressure. However severe pain can lead to parasympathetic over domination leading to hypertension. This is a physiological basis for someone developing syncope in server pain.
ENDOCRINE EFFECTS.
Various hormones affect the blood pressure in human’s cardinal amongst these are Noradrenelin and Adrenalin which are the sympathetic neurotransmitters and the pharmacological basis of treatment of Hypertension revolves round this physiological knowledge. Adrenalin and Noradrenalin which are sympathetic Nemo transmitter will lead to increase in blood pressure whereas Acetyl choline which is a para sympatric Nemo-transmitter leads to a fall in blood pressure. The adrenergic effort is on both blood pressure and the Heart and so it affects the pumping action of the Heart, peripheral resistance. Elasticity and mimicks the auto Mobic nervous system effect of the control of blood pressure.
Besides there is also vasopressin or antidiuretic hormone (ADH) which is a strongly vasoconstriction effect on the blood vessels. This is not as significant in the control of blood pressure as Noradrenalin or adrenaline of the endocrine factors a endocrine factors, a clinical situation called phaechromocytoma does exist where by, there is excessive release of catecholamine’s leading to sustained hypertension. So endocrine factors in control of blood pressure are important.
Gastrin a gastrointestinal hormone has been known to have varying effects on the blood pressure depending on the dose but its effect on the normal control of blood pressure in man is questionable.
CHEMICAL OR IONIC EFFECTS
Many different chemical factors and was affect blood pressure by either dilating or constricting local blood vessels. Though the roles of these substances in the overall regulation of the circulation generally are not known, their specific effects can be listed as follows: an increase in ‘’calcium’’ concentration causes ‘’’vasoconstriction’’. This results from the general effect of calcium to stimulate smooth muscle contraction.
An increase in magnesium ions concentration causes ‘’vasodilatation’’, for magnesium, Lorries like potassium ions. Inhibit smooth muscle generally.
Increased ‘’sodium ions concentration causes ‘’arteriolar dilatation’’ this results from an increase in osmolality of the fluids rather than from a specific effect of sodium ion itself. The raised osmolality of the blood caused by increased quantities of ‘’Glucose’’ or other on vasoactive substance also caused arteriolar dilatation. Decreased osmolality causes arteriolar constriction.
An increase in Hydrogen ion concentration (decrease in PH) causes dilatation of the arterioles. A slight decrease in Hydrogen ion concentration causes ‘’Arteriolar constriction, but an intense decrease causes ‘’Dilatation’’, which is the same effect as that which occurs with increased hydrogen ion concentration. Changes in carbon dioxide (CO2) concentration have almost no direct effect on the degree of constriction of local blood vessels, however CO2, acting on vasomotor centre, has extremely powerful vasoconstrictor effect. Also, CO2, can cause dilatation indirectly by increasing the hydrogen ion concentration.
The adenosine compounds including adenosine itself, AMP, AOP. ARB all cause vasodilatation.
VASOMOTOR CENTRE ACTIVITY
The vasomotor centre is located in the lower one-third(x) of the pons and the upper two-thirds (1,3) of the medulla. It has a predominant effect on the control of blood pressure by its action on the diameter of the vessels. The vasomotor centre is affected by higher centres including cortex and the limbic system. Their effect can either be excitatory or inhibitory to the vasomotor centre. Carbon-dioxide also affects the vasomotor centre and is positive. Oxygen lack will also positively stimulate the vasomotor centre leading to generalised vasoconstriction and increase in blood pressure. Impulses from reformatory centre can also affect the vasomotor centre positively or negatively thereby leading to changes in blood pressure. Impulses from Baroreceptor have a negative influence on vasomotor venter which will lead to vasodilatation which will lead to vasodilatation and in so doing will correct the increased pressure that originally stimulated the Baroreceptors.
Chemoreceptors have either positive or negative influence depending on the degree of their concentration in the vasomotor centre.
Other afferents from the somatic and the visceral regions can also affect the vasomotor centre e.g. in severe dilatation of the gut which leads to Hypotension die to parasympathetic over domination.
KIDNEYS
The kidneys play an important role in control of blood pressure in man. When they are diseased e.g. in glomerular nephritis and pyelonephritis. They will affect the blood pressure in man and this is the physiological basis for our investigation of kidney disease for all hypertensive cases.
OTHER FACTORS.
Besides the factors, there are some other factors some of which have not been properly elucidated which lead to hypertensive state in man and are collect