CHAPTER ONE: INTRODUCTION

1.1   Background of the Study
The word hypertension is defined as a persistence increase in systemic arterial blood pressure (Sembulingam and Sembuligam, 2006). Clinically, when the systolic pressure remains elevated above 140mmHg and diastolic pressure remains elevated above 90mmHg, it is considered as hypertension. The prevalence varies with age, race, education, occupation and many other variables (Benowitz, 2009). In Nigeria for example, the true incidence of hypertension remains unknown but its prevalence among male and female is estimated to be 11.2% with age adjusted figure of 9.3% (Nurudeenet al., 2013). This translates into approximately 13.4 million Nigerians becoming hypertensive at the age of 15years and above, using the projected national population census figure of 120million (Akinkungbe, 1998). In fact, hypertension is reported to be next to malaria as most serious health problems in developing tropical countries (Agunwa, 1988).
The global dimension of hypertension is immense, as it ranks the most common cardiovascular ailment afflicting about one billion people in the world and causing roughly 7.1 million deaths annually (Brundtland, 2002). Hypertension is said to be the most common cardiovascular disease among Africans and congestive cardiac failure its commonest complication (Akinkungbe 1972, 1985). Earlier studies suggested that hypertension was rare in African population (Sharper et al., 1969, Pobeeet al., 1977), however, epidemiological transition, urbanization, adoption of urban and foreign lifestyles and improved case findings, among others, have made hypertension more prevalent as shown in some studies (Cooper et al., 1998). The last Nigerian National Non-communicable Disease Survey (NNCDS)conducted in 1997 reported 11.4% prevalence of adult hypertension, varying from 14.8% in urban to 9.8% in rural residences respectively. However, a report on Nigeria from the World Health Organization says that, in 2008, the probability of dying between the ages of 30 and 70 years from any of the 4 main NCD is 20% while adult risk factors for raised blood pressure was 34.8% – 33.5% for males and 36.1% for females (WHO, 2008). Another report estimated 38.6% of males and 41.2% of females in the country suffered from hypertension in 2012, figures that were above the regional average for both genders (WHO, 2012). The high prevalence of hypertension together with its deleterious effect on health makes it a major public health problem.
Angiotensin I Converting Enzyme (ACE) is a glycoprotein with peptidyl dipeptide hydrolase activity which cleaves Angiotensin I to produce Angiotensin II in the blood. The powerful vasoconstrictive action of Angiotensin II and its stimulatory action on the synthesis and release of aldosterone favours retention of sodium and water. It also hydrolyzes and inactivates bradykinin, a peptide with a powerful vasodilatory action (Hernandez-Ledesmaet al., 2003; Wong et al., 2004). The utilization of synthetic ACE inhibitors, such as the well-known captopril, provides definitive positive health effects and is considered an important therapeutic approach in the treatment of high blood pressure, though the use of these pharmacological drugs is not advisable in healthy or low-risk populations (Carretero and Oparils, 2000).
The evidence that certain flavonoid-rich natural products can induce reductions in blood pressure and inhibit ACE activity opens the possibility that their consumption may mimic synthetic ACE inhibitors and provide preventive health benefits probably avoiding adverse side effects associated with the synthetic ones in current usage (Actis-Gorettaet al., 2006). If the formation of angiotensin II and the activation of vasodilatorykinins are suppressed by selective ACE inhibitors, there will be a lowering of blood pressure. Some plant products and substances isolated from plants show inhibitory effects on ACE (Farzamirad and Aluko, 2008).
There are 11 ACE inhibitors approved for therapeutic use which can be sub-classified into three groups based on their chemical composition (Jimshenna and Gowda, 2011).

1. Sulfhydryl - containing inhibitors e.g Captopril, Zofenopril.
2. Dicarboxylate - containing inhibitors e.gEnalapril, Lisinopril, Ramipril.
3. Phosphate - containing inhibitors e.g. Fosinopril

Due to the adverse effect observed with the use of synthetic ACE inhibitors, there is a need to look into natural ACE inhibitors from plants.

Combretummicranthum has a number of uses, traditionally it is used as, antihypertensive,diuretic, anti-diarrhoeal, anti-syphilis, antimalarial agent, and to treat hepatitis, jaundice and bronchitis (Udumaet al., 2010). Stefano et al (2014) reported the antimicrobial potency of the leaf extract. Phytochemical studies carried out in the genus Combretum including Combretummicranthumhave demonstrated the occurrence of many classes of constituents,includingtriterpenes, flavonoids, lignans and non-protein amino acids, among others (Touaet al., 2015; Pietrovskiet al., 2006).

1.2   Statement of the Problem
Hypertension is a risk factor for cardiovascular disease. It is the most common and persistent serious health problem, It affects 20-45% of the active population and carries a high risk factor of arteriosclerosis, stroke, myocardial infarction and end stage renal diseases (Jung et al., 2006). It affects 15-25% of adult and 50-60% of elderly people (Gokce, 2004). It ispredicted that the rate of hypertension would increase by 60% in 2025 (Kearney et al., 2005). More than 40 million people worldwide are currently receiving synthetic Angiotensin converting enzyme inhibitors which are associated with the development of adverse consequences such as; Kidney failure, angioedema, hypotension, decrease in white blood cells etc.

1.3   Justification of the Study
Several plants have been reported to have been used in the management of hypertension with no or less side effects. Combretummicranthumhas numerous medicinal applications and it is used traditionally for the treatment of hypertension among the local people. Recently it has been hypothesized that oxidative stress is a key player in the pathogenesis of human hypertension (Rodrigo et al., 2011; Montezano and Touyz, 2012). Hence there is a need to simultaneously evaluate the antioxidant potency and Angiotensin converting enzyme inhibitory activity with the aim of identifying hypertensive drug candidate from plants.

1.4   Aim of the Study
The aim of the study is to investigate the effect of aqueous extract of Combretummicranthumleaves on angiotensin converting enzyme and its Antioxidantproperties.
1.4.1 Specific objectives
The specific objectives of the present study are to:

1. Evaluate the ACE inhibitory activity of aqueous extract of Combretummicranthum leaves.
2. Subject the aqueous extract of the leaves of Combretummicranthum to column chromatography
3. Determine the antioxidant potency and ACE inhibitory activity of fractions from the column chromatography of the aqueous extract.
4. Subject the fraction with the best ACE inhibitory activity to GC-MS.