**2. Hypertension**

Hypertension, also known as raised blood pressure (BP), is a chronic medical condition and a slow progressive disease defined by a mean systolic BP (SBP) of at least 140 mm Hg and/or a diastolic BP (DBP) of at least 90 mm Hg [4, 15- 16]. In the USA, the seventh report of the Joint National Committee (JNC 7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure has classified measured BP into different schemes and introduced a new classification referred to as "Prehypertension" [15]. Prehypertension was not defined as a disease-state but represented BP measurements of individuals at high risk of developing hypertension (Table 1). Hypertension has been classified into primary hypertension or essential hypertension (EH) and secondary hypertension (SH). They have respectively unknown and known aetiology.


**Table 1.** JNC 7 Classification of blood pressure [4, 15]

Hypertension is a major public health problem responsible for 51% of stroke deaths and 45% of coronary heart diseases deaths [1, 3]. It represents the leading global risk factor of mortali‐ ty, about 12.8% of global death [3] and is also reported to affects both man and woman [17]. Additionally, the prevalence of hypertension is reported to increase with body weight and advancing age [2, 15-16, 18]. Conversely, hypertension in children has been reported, especial‐ ly, in overweight and obese children [19].It has been observed that Black men and women have the highest prevalence of total hypertension [15-16]. Furthermore, while the large proportion ofthepopulationsuffers fromEH(90-95%),only5-10%amongthe cases suffers fromSH[20-24]. It has been reported that most individuals have an uncontrolled hypertension because the diseaseispredominantlya"silent"diseasewhichisasymptomatic [17].Epidemiological studies estimated that in the United States, one in five adultremains unaware of his diseased-state [16]. Nonetheless, with the rise of campaign aimed at increasing hypertension awareness and treatment, the prevalence of uncontrolled hypertension is declining in developed countries, when compared to developing countries [16, 18]. Actually, the low- and middle-income countries, especially Sub-Saharan African countries record an increase in the overall rate of hypertension mostly because of the severe financial constraints, limited set of health services, low access to facilities and low level of awareness, control, treatment campaigns [4].

#### **2.1. Aetiology of essential hypertension**

The aetiology of EH remains a mystery. Even though, EH is the commonest form of hyper‐ tension (90% - 95% of all cases), the underlying defects triggering its onset are not known. This explains the difficulty in finding a definite cure. It has been theoretically proposed (Mosaic Theory of Dr Irvine Page) that the aetiology of EH is multifactorial with genetic, environmental, anatomical, adaptive, neural, endocrine, humoral, haemodynamic risk factors and that those different risk factors interlink together to cause hypertension [25-27]. Some of these risk factors are described below:

## *2.1.1. Environmental risk factors*

Various dietary habits and unhealthy lifestyle have also been identified to play a major role in the pathogenesis of hypertension such as:

**•** Pollutants

chapter, a brief explanatory overview of hypertension and its implication in CVD will be given followed by a summary of potential ability of *Parkia biglobosa* to modulate health, especially

Hypertension, also known as raised blood pressure (BP), is a chronic medical condition and a slow progressive disease defined by a mean systolic BP (SBP) of at least 140 mm Hg and/or a diastolic BP (DBP) of at least 90 mm Hg [4, 15- 16]. In the USA, the seventh report of the Joint National Committee (JNC 7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure has classified measured BP into different schemes and introduced a new classification referred to as "Prehypertension" [15]. Prehypertension was not defined as a disease-state but represented BP measurements of individuals at high risk of developing hypertension (Table 1). Hypertension has been classified into primary hypertension or essential hypertension (EH) and secondary hypertension (SH). They have respectively

**Blood pressure (mm Hg)**

Hypertension is a major public health problem responsible for 51% of stroke deaths and 45% of coronary heart diseases deaths [1, 3]. It represents the leading global risk factor of mortali‐ ty, about 12.8% of global death [3] and is also reported to affects both man and woman [17]. Additionally, the prevalence of hypertension is reported to increase with body weight and advancing age [2, 15-16, 18]. Conversely, hypertension in children has been reported, especial‐ ly, in overweight and obese children [19].It has been observed that Black men and women have the highest prevalence of total hypertension [15-16]. Furthermore, while the large proportion ofthepopulationsuffers fromEH(90-95%),only5-10%amongthe cases suffers fromSH[20-24]. It has been reported that most individuals have an uncontrolled hypertension because the diseaseispredominantlya"silent"diseasewhichisasymptomatic [17].Epidemiological studies estimated that in the United States, one in five adultremains unaware of his diseased-state [16]. Nonetheless, with the rise of campaign aimed at increasing hypertension awareness and treatment, the prevalence of uncontrolled hypertension is declining in developed countries,

Normal lower than 120 lower than 80 Prehypertension 120 to 139 80 to 89 Hypertension 140 or higher 90 or higher Stage 1 140 to 159 90 to 99 Stage 2 160 or higher 100 or higher

**SBP DBP**

CVD.

**2. Hypertension**

350 Antioxidant-Antidiabetic Agents and Human Health

unknown and known aetiology.

**Table 1.** JNC 7 Classification of blood pressure [4, 15]

**JNC 7 category**


The consequences of this adopted lifestyle give the rise to metabolic and physiological alterations which mediate the pathogenesis of hypertension and promotes other deleterious conditions such as hyperglycaemia (principal characteristic of diabetes) and hyperlipidaemia (principal characteristic of obesity) [29].

#### *2.1.2. Hereditary risk factors*

Genetic factors are thought to play a prominent role in the development of essential hyper‐ tension, especially genetic abnormalities of the baroreceptor system. However, the genes for hypertension have not yet been identified.

The baroreceptor system consists of nerves ending receptors sensitive to stretch, pulse rate and pressure changes of the blood vessels [30]. They are present on the wall of large arteries such as the aortic arch and the carotid sinus (Figure 1). They stand as the first line of neural control system over blood pressure fluctuation and constitute a short term regulation of BP [31-33]. With a significant change in BP, baroreceptors transmit impulses to central nervous system (CNS)to activate a "feedback" mechanism from autonomous nervous system calledbarorecep‐ tor reflex or baroreflex. The baroreceptor autonomous reflex restores the BP to normal values [30-33].Ithasbeenreportedthatthatlackofbaroreflexsensitivityisassociatedwiththepresence of a family history of hypertension [32, 34]. This shows that hypertension could be initiated from specific hereditary genetic abnormalities involving baroreceptors sensitivity [32, 34].

and increased arterial resistance [25, 48]. For example, the renin angiotensin system (RAS) is a central system involved in the regulation of BP and electrolytes homeostasis. Briefly, with a decrease in BP, kidneys prorenin are converted into active renin. Active renin cleaves the hepatic precursor protein angiotensinogen into the inactive angiotensin I (Ang I) [43, 49]. Then, the angiotensin converting enzyme (ACE) hydrolyses two principal molecules. Firstly, ACE cleaves the inactive Ang I to give active vasoconstrictor hormone Angiotensin II (Ang II). Angiotensin II, not only increases BP by constricting blood vessels but also causes the adrenal gland to release aldosterone, a hormone which increase BP through renal retention of sodium and water (increase of blood volume) and decrease excretion of potassium [42-43, 49]. Secondly, ACE which is a kininase II interact with the kinin-kalllikrein system and inactivate the vasodilator bradikinin by releasing pentapeptide Arg-Pro-Pro-gly-Pheo and tripeptide Ser-Pro-Phe fragments [42]. Therefore, failure to regulate the activated RAS at different level could lead to hypertension. Another example of system dysfunction involved the failure to

Potential Role of *Parkia biglobosa* in the Management and Treatment of Cardiovascular Diseases

The aetiology of SH has been often identified with an underlying illness which indirectly increases BP. It has also been demonstrated that SH can emerge from drugs intake and health conditions such as pregnancy [15, 20, 50-52] (Table 2). Therefore, the treatment of SH is

RENOVASCULAR DISEASES/RENAL ARTERY

http://dx.doi.org/10.5772/57229

353

•Arteriovenous malformation of the renal

•Atherosclerotic renal artery diseases

•Fibromuscular dysplasia •Renal artery embolism

STENOSIS

artery

associated along with the treatment of the identified underlying factors.

regulate the increased activity of norepinephrine [48].

**2.2. Aetiology of secondary hypertension**

Renal diseases RENAL PARENCHYMAL DISEASES:

Vascular diseases •Coarctation of aorta

Neurological diseases •Brain tumours

Drugs •Oral contraceptive pills

**Table 2.** Causes of secondary hypertension [52]

Endocrinal and metabolic

diseases

•Glomerulonephritis •Polycystic kidney diseases •Diabetic nephropathy •Hydronephrosis

•Aortoarteritis

•Encephalitis

•Cushing syndrome •Pheochromocytoma

•Chronic kidney disease (CKD)

•Primary aldosteronism (Conn Syndrome), •Primary sodium retention (Liddle's Syndrome)

•Non-steroidal anti-inflammatory medications

•Drug Abuse (Cocaine, Alcohol)

**Causes Examples**

In addition, hereditary genetic abnormalities of the neuroendocrine regulation of barorecep‐ tors have similarly been recognised as predictors of EH. For instance, studies have related overexpression of Chromogranin A (Cg A) in plasma, adrenal medulla and sympathetic neurons to essential hypertension in both clinical and experimental models [25, 35]. Similarly, Cg A loci genetic polymorphism was related to hypertension [36]. Chromogranin A is a prohormone stored and released with catecholamine (epinephrine, norepinephrine and dopa‐ mine) by exocytosis [37-38]. It is believed that Cg A influence sympathetic tone since it is a prohormone for active peptides with regulatory properties, namely vasostatin, pancreastastin and catestatin [37, 39]. Catestatin exhibits catecholamine release-inhibitory function and may function as a vasodilator [40-41]. Decreased circulating level of catestatin has been related to EH because it increases adrenergic pressor response by no longer exerting antagonism to neuronal nicotinic acetylcholine receptor [40-41].

Several genetic factors can affect the renin-angiotensin-aldosterone system and indirectly result in hereditary hypertension. For instance, deficient formation of kinin components (proteins that act locally to induce vasodilatation) in the body may also lead to hypertension and development of CVD. Renal kinin-kallikrein system helps to excrete excess sodium from the biological system [42]. Therefore, a reduction in renal expression of kinin-kalllikrein system can also be identified as a genetic factor for hypertension as a result of accumulation of sodium in the body. Consequently, diminished urinary kallikrein (sub-group of serine protease) excretion could represent a genetic marker of hereditary hypertension [42-43].

#### *2.1.3. Haemodynamic, endocrine, neural, anatomical risk factors*

The cardiovascular system ensures the supply of blood to all organs and tissues via distensible blood vessels such as arteries, veins and capillaries of the circulatory system (peripheral and pulmonary). Blood pressure represents the force with which the blood pushes against the wall of the arteries. At physiological level, factors such as blood volume, cardiac output, diameter of artery lumen, and elasticity of artery determine BP [44-45]. In addition, different systems contribute to the short-term and long-term regulation of BP such as:


Therefore, any molecular and physiological dysfunction affecting the regulation of BP can be associated with the pathogenesis of hypertension such as dysfunctions of the renin angiotensin system (RAS), dysfunctions in electrolytes homeostasis, dysfunctions of the endocrine system and increased arterial resistance [25, 48]. For example, the renin angiotensin system (RAS) is a central system involved in the regulation of BP and electrolytes homeostasis. Briefly, with a decrease in BP, kidneys prorenin are converted into active renin. Active renin cleaves the hepatic precursor protein angiotensinogen into the inactive angiotensin I (Ang I) [43, 49]. Then, the angiotensin converting enzyme (ACE) hydrolyses two principal molecules. Firstly, ACE cleaves the inactive Ang I to give active vasoconstrictor hormone Angiotensin II (Ang II). Angiotensin II, not only increases BP by constricting blood vessels but also causes the adrenal gland to release aldosterone, a hormone which increase BP through renal retention of sodium and water (increase of blood volume) and decrease excretion of potassium [42-43, 49]. Secondly, ACE which is a kininase II interact with the kinin-kalllikrein system and inactivate the vasodilator bradikinin by releasing pentapeptide Arg-Pro-Pro-gly-Pheo and tripeptide Ser-Pro-Phe fragments [42]. Therefore, failure to regulate the activated RAS at different level could lead to hypertension. Another example of system dysfunction involved the failure to regulate the increased activity of norepinephrine [48].

#### **2.2. Aetiology of secondary hypertension**

tor reflex or baroreflex. The baroreceptor autonomous reflex restores the BP to normal values [30-33].Ithasbeenreportedthatthatlackofbaroreflexsensitivityisassociatedwiththepresence of a family history of hypertension [32, 34]. This shows that hypertension could be initiated from specific hereditary genetic abnormalities involving baroreceptors sensitivity [32, 34].

In addition, hereditary genetic abnormalities of the neuroendocrine regulation of barorecep‐ tors have similarly been recognised as predictors of EH. For instance, studies have related overexpression of Chromogranin A (Cg A) in plasma, adrenal medulla and sympathetic neurons to essential hypertension in both clinical and experimental models [25, 35]. Similarly, Cg A loci genetic polymorphism was related to hypertension [36]. Chromogranin A is a prohormone stored and released with catecholamine (epinephrine, norepinephrine and dopa‐ mine) by exocytosis [37-38]. It is believed that Cg A influence sympathetic tone since it is a prohormone for active peptides with regulatory properties, namely vasostatin, pancreastastin and catestatin [37, 39]. Catestatin exhibits catecholamine release-inhibitory function and may function as a vasodilator [40-41]. Decreased circulating level of catestatin has been related to EH because it increases adrenergic pressor response by no longer exerting antagonism to

Several genetic factors can affect the renin-angiotensin-aldosterone system and indirectly result in hereditary hypertension. For instance, deficient formation of kinin components (proteins that act locally to induce vasodilatation) in the body may also lead to hypertension and development of CVD. Renal kinin-kallikrein system helps to excrete excess sodium from the biological system [42]. Therefore, a reduction in renal expression of kinin-kalllikrein system can also be identified as a genetic factor for hypertension as a result of accumulation of sodium in the body. Consequently, diminished urinary kallikrein (sub-group of serine protease)

The cardiovascular system ensures the supply of blood to all organs and tissues via distensible blood vessels such as arteries, veins and capillaries of the circulatory system (peripheral and pulmonary). Blood pressure represents the force with which the blood pushes against the wall of the arteries. At physiological level, factors such as blood volume, cardiac output, diameter of artery lumen, and elasticity of artery determine BP [44-45]. In addition, different systems

**•** The humoral secretion of vasoconstrictors and vasodilators substances such as acetylcho‐

**•** The kidneys regulation of BP via renal body fluid feedback, namely the renin-angiotensin-

Therefore, any molecular and physiological dysfunction affecting the regulation of BP can be associated with the pathogenesis of hypertension such as dysfunctions of the renin angiotensin system (RAS), dysfunctions in electrolytes homeostasis, dysfunctions of the endocrine system

excretion could represent a genetic marker of hereditary hypertension [42-43].

*2.1.3. Haemodynamic, endocrine, neural, anatomical risk factors*

**•** The nervous system baroreceptor reflex [46].

line, atropine [47].

contribute to the short-term and long-term regulation of BP such as:

aldosterone system and the pressure natriuresis [31, 43].

neuronal nicotinic acetylcholine receptor [40-41].

352 Antioxidant-Antidiabetic Agents and Human Health

The aetiology of SH has been often identified with an underlying illness which indirectly increases BP. It has also been demonstrated that SH can emerge from drugs intake and health conditions such as pregnancy [15, 20, 50-52] (Table 2). Therefore, the treatment of SH is associated along with the treatment of the identified underlying factors.


**Table 2.** Causes of secondary hypertension [52]
