Chapter 2: Blood Pressure and Hypertension



2.1  Introduction

2.2  Hypertension

2.3  History of Blood Pressure Measurement

2.4  Blood Pressure Regulation

2.5  Non-Invasive Blood Pressure Measurement Techniques

2.6  Therapeutic Principles

2.7  Recent Hypertension Research and Current Topics


2.1 Introduction

One of the most important determinants of cardiovascular function is the blood pressure. The blood pressure is defined as the force or pressure of the blood against the vessel walls of the cardiovascular system. Blood pressure is transient and fluctuates as a result of the pulse cycle. When the heart contracts, pushing blood out of the heart and into the vessels of the cardiovascular system, the blood pressure increases, and the maximum pressure in the vessel is known as the systolic blood pressure (SBP). In contrast, when the heart relaxes in between heart beats (pulses), the pressure in the vessels decreases and the lowest pressure is referred to as the diastolic blood pressure (DBP). Clinically, the systolic and diastolic blood pressures are denoted as the systolic pressure over the diastolic pressure. For example, a systolic pressure of 120 mmHg and diastolic pressure of 80 mmHg, would be referred to as “120 over 80”. Although pressure can be recorded in several different units, clinically, blood pressures are measured in millimeters of mercury (mmHg).

The systolic and diastolic pressures are two of several independent values representing the cardiovascular performance of the heart. Clinically, these two values can be combined to form an average blood pressure, called the mean arterial pressure, which reflects the influence of the systolic and diastolic pressure on the cardiovascular system. The mean arterial pressure (MAP) is the time weighted average of the blood pressure during the entire pulse cycle. During a single pulse, approximately one third of the cycle is maintained near the systolic pressure, and two thirds of the cycle is maintained near diastolic pressure. Therefore, estimated:

MAP = 1/3 SBP + 2/3 DBP

The calculation of the main arterial pressure is an excellent way to evaluate the stress on the walls of the vessels. This new parameter may be useful to quickly evaluate excessive load on the cardiovascular system in the future.


2.2 Hypertension:

Blood pressure not only fluctuates due to the pulse cycle, but also as a result of external factors. Diet, stress, and physical exertion are only a few of the factors that may influence blood pressure changes. However, in healthy individuals, the blood pressure will return to “normal” when external factors are minimized or negligible. In contrast, when the blood pressure remains high for an extended period of time, an individual may be diagnosed as having high blood pressure/hypertension. Hypertension is a serious disorder that affects approximately 50 million American adults. Hypertension is not necessarily difficult to treat, however, it is hard to detect because it shows no symptoms and therefore is known as the “silent killer.” Some people claim that they can feel high blood pressure, but estimates are rather unreliable. Only by performing regular measurements with an accurate method can one assess the blood pressure and cardiovascular health.

In recent years, medical research has revealed a link between hypertension and other cardiovascular diseases. The elevated blood pressure resulting from hypertension can cause excessive stress on the heart and blood vessels. As a result of the excessive load, the risk of heart attack and stroke increases substantially. In order to help prevent cardiovascular disease, early detection of hypertension is critical. The National Institute of Health (NIH) has developed guidelines (1997) in order to assess blood pressure status. The guidelines have been developed to more clearly define hypertension as a cardiovascular risk factor and provide direction for intervention.

The blood pressure classifications, defined by the NIH, are based on the average of at least two blood pressure measurements for an adult, assuming they are not on anti hypertension medication nor actually ill.


Systolic (mm Hg)

Diastolic (mm Hg)







High Normal






stage 1



stage 2



stage 3

> or equal 180

> or equal to 110

When the systolic and diastolic blood pressures fall into different categories, the higher category should be selected to classify the blood pressure status. For example, 160/92 should be classified as “moderate” and 180/92 should be classified as “very severe.” In addition, a classification of Isolated Systolic Hypertension (ISH) may be made when SBP>140 and DBP<90. Therefore, a blood pressure of 160/82 should be classified as "ISH".

Once a blood pressure classification has been established, the following guidelines should be used as a reference for follow-up.

Initial Screening Blood Pressure (mmHg)

Initial Screening Blood Pressure (mmHg)




Followup Recommended



Recheck in 2 years



Recheck in 1 year



Confirm within 2 months



Evaluate or refer to source of care within 1 month



Evaluate or refer to source of care immediately, or within 1 week depending on clinical situation.


By regularly calculating the blood pressure and following the structure guidelines developed by the NIH, one can reduce hypertension and the risk of cardiovascular disease.


2.3 History of Blood Pressure Measurement

In 1733, Reverend Stephen Hales published one of the first methods of blood pressure measurement. He developed a technique in which a glass tube could be inserted into the arteries of the neck of a horse. By holding the glass tube in an upright position, the blood would be pumped out of the neck and into the tube by the pumping of the heart. As a result, the level of the blood in the tube could determine the blood pressure. Unfortunately for the horse, since the blood in the tube was not returned to the cardiovascular system, the measurement was irreversible.

The tools for the direct assessment of blood pressure have come a long way since the early 1700’s. Today, direct techniques of blood pressure evaluation called catheterization take place in hospitals around the world daily. Catheterization involves inserting a pressure transducer known as the catheter, into different areas of the cardiovascular system. For instance, in order to understand the pressure changes inside the left ventricle of the heart, the catheter is inserted into the femoral artery of the patient (the groin area), guided up the femoral artery into the aorta, past the aortic valve and into the left ventricle. The results of the catheter pressure are displayed as a waveform on the screen of a computer system. Although discomforting, in most cases the patient experiences no long-term side effects.

Catheterization procedures, however, have several drawbacks. First, the procedures can only be performed in a sterile environment such as a hospital under the supervision of a cardiologist. Second, due to the need for infection control and professional personnel, most catheterization procedures are time consuming and extremely expensive ranging in the thousands of dollars. Finally, as a result of any invasive procedure, the patient is under the risk of complications such as infection, which may lead to very serious consequences. As a result of these weaknesses, great time and effort was taken in the development of new fast and convenient methods of blood pressure measurement. The development of indirect blood pressure measurement techniques has reduced cost, time and risk of complications to the patient making indirect blood pressure assessment the standard technique for regular blood pressure evaluation.



2.4 Blood Pressure Regulation



Homeostasis is defined as the condition of constancy of the “internal environment” in terms of its cells, tissues, and organs. Thus in blood pressure regulation, homeostasis will tend to stabilize the blood pressure, maintaining it at a steady resting state. For example, if a person exercises, the heart rate will increase, inducing higher blood pressure. Homeostasis will accommodate the body through various mechanisms to decrease the heart rate and reduce the high blood pressure. Homeostasis is the primary basis by which normal body functions are maintained in order to sustain life.

Negative Feedback System:

One of the most important techniques for maintaining homeostasis is the negative feedback system. The system works to maintain a physiological set-point of the body by sensing changes and returning the body to the original set-point. That means, if a physiological disturbance occurs, the body via a negative feedback system will counteract the disturbance and try to return the body to its normal set-point. There might be more than one negative feedback systems that can counter the changes of a particular disturbance (as is the case of blood pressure regulation). Whenever the condition of constancy is deviated and corrections are not possible, damage to the body and death can result.

Some of the important tools to regulate blood pressure in the body are as follows:


Baroreceptors are pressure sensors that monitor blood pressure. One population of these receptors is located in the walls of the common carotid artery, forming the carotid sinus. Others are scattered throughout the wall of the aortic arch. They are very sensitive to blood pressure leaving the heart and act as the sensor to keep the overall pressure of the heart at a set point. If the blood pressure begins to fall, baroreceptors activation decreases, and the autonomic nervous system acts to increase blood pressure. In contrast, if the blood pressure increases, baroreceptor activation also increases, and the autonomic nervous system must act to decrease the blood pressure.


Smooth muscles of most vessels are innervated by the autonomic nervous system. When blood vessels “dilate” or vasodilate through relaxation of the smooth muscles in the wall of the vessels, the radius and compliance of the vessels increase. Not only does the larger opening in the vessels increase blood flow through the vessels, but also the larger compliance gives the vessels the ability to stretch with an increased load, permitting an even greater volume of blood flow through the vessels.


Similar to vasodilation, vasoconstriction is also controlled by the autonomic nervous system, and causes the smooth muscles in the wall of the blood vessel to “constrict” or vasoconstrict. As a result of vasoconstriction, the vessels stiffen and become less compliant. However, the effects of vasoconstriction in the arteries and veins are quite different. In arterial vasoconstriction (major site of flow resistance in the body), the effect is to redirect blood flow and increase the total peripheral resistance. In the veins, vasoconstriction does not affect total peripheral resistance as greatly as in the arteries, which have lower overall compliance (stiffer). Instead, the primary outcome of vasoconstriction is to decrease the venial wall compliance, which decreases the volume of blood within the veins.

Precapillary Sphincters:

Located at the entrance to the capillary vessels are precapillary sphincters consisting of a single smooth muscle fiber per sphincter. These capillary “gate- keepers” open and close in response to changes in their immediate environment, such as blood pressure. This helps to maintain blood pressure in the venous circulation. Another important function of the precapil lary sphincter is to prevent back flow of blood, driving blood flow in one direction.



2.5 Non-Invasive Blood Pressure Measurement Techniques

During the past 90 years two primary methods of non-invasive blood pressure assessment have been developed. Although they depend on different mediums in order to detect the blood pressure signal, both the auscultatory and oscillometric techniques depend on the use of an air filled cuff to occlude the brachial artery. Cuff measurement principles are based on simple fundamental physics. As illustrated in Figure 2.1, when the cuff is inflated to a pressure greater than the maximum arterial pressure (systolic pressure), no blood flows through the artery under the cuff. When the cuff slowly deflates to a pressure equal to the systolic pressure, blood begins to flow through the artery (figure 2.2). As the cuff pressure continues to deflate, the oscillation of blood jetting through the artery begins to flow stronger. When the cuff no longer occludes the artery and the artery has returned to the original state (figure 2.3), the minimum pressure (diastolic pressure) is observed. Both indirect methods of assessment depend on this simple physical phenomenon.


Figure 2.1         Figure 2.2             Figure 2.3



The auscultatory method of blood pressure determination depends on sound to transmit the blood pressure signal. The physical phenomenon due to the cuff occluding the brachial artery can be detected by the human ear through a stethoscope. The Korotkoff sound signals, as they are known, correlate to characteristics of the cuff deflation principle. As the pressure decreases from above the systolic pressure due to the deflation of the cuff, the Korotkoff sounds become audible and then fade away as the cuff pressure decreases. The systolic pressure is the pressure at which the Korotkoff sounds first become audible. The sounds then become muffled as the blood jets through the brachial artery and finally disappear. The pressure at which the sounds become extremely muffled and disappear is the diastolic pressure. Unfortunately, inaccurate blood pressure determination may occur due to hearing problems or noisy backgrounds, in addition to inherent limitations of the human ear. However, an automated auscultatory technique using a microphone may improve inherent limitations of the manual technique providing more accurate blood pressure determinations.


The oscillometric method of blood pressure determination is dependent on pressure changes in the brachial artery as air released from a pressure cuff. The pressure volume coupling between the brachial artery and the cuff is fundamental in the determination of blood pressure. A change in blood pressure within the artery causes a change in volume of the brachial artery due to the elasticity of the vessel. The change in volume of the artery causes a change in volume in the cuff due to the coupling of the cuff to the arm. A sensitive pressure transducer that creates a digital signal detects the corresponding pressure change within the cuff. The signal is displayed as a blood pressure waveform (figure 2.4) in which blood pressure can be calculated. The waveform is recorded as the cuff pressure deflates from a cuff pressure greater than the systolic pressure to cuff pressure that is less than the diastolic pressure. Although traditional oscillometric methods use the amplitude of the signal to detect the blood pressure, the DynaPulse utilizes pattern recognition. A new, patented algorithm based on this technique is used to determine the systolic, diastolic, and mean arterial pressure from the non-invasive blood pressure waveform. The single pulse pressure wave (figure 2.5), which is normalized to the systolic and diastolic pressures, is utilized to examine individual pulse behaviors.



Figure 2.4



Figure 2.5




2.6 Therapeutic Principles


Systemic hypertension is a health threat to the person as a whole, since the untreated disease shortens life expectancy with approximately 20 years. Target organs for damage are the heart, aorta, brain, eyes and the kidneys.

The positive effect on life expectancy of a moderate reduction of an abnormally high systemic arterial blood pressure is well documented.

The simple resistance model is applied for the therapy of systemic hypertension. The driving pressure in the systemic circulation is equal to the cardiac output multiplied with the Total Peripheral Vascular Resistance (TPVR).

The cardiac output is equal to the cardiac frequency multiplied with the stroke volume, and the stroke volume depends of the total blood volume. TPVR depends of the degree of contraction of the resistance vessels and of the distensibility (eg, specific compliance) of the arterial system.

Principally, systemic hypertension is therefore treatable through one or more of the following strategies:

1.   Reduction of the total blood volume (and thus the stroke volume) with diuretics results in reduction of the driving pressure,

2.   Reduction of the cardiac frequency reduces cardiac output and thus the driving pressure,

3.   Reduction of TPVR with vasodilatators reduces the driving pressure.

Two strategies of therapy and their combination are available: Change of life style with or without drug therapy. Drug therapy must usually be continued for the lifetime of the patient.

Life style modifications (relaxed duration exercise and healthy habits):

In healthy individuals, the opening of resistance vessels during exercise typically reduces the TPVR to 30% of the value at rest. This vasodilatation expresses an enormous capacity, which is only present in the resistance vessels of the striated muscular system at large. The only natural way to break the vicious circle described above is to maintain the dilatation capacity throughout life by frequent use of the locomotor system. The exercise must include large muscle groups for some time. The exercise must be relaxed and comfortable in order to become a life style. Other beneficial effects of relaxed duration exercise (such as walking, golf, jogging, swimming, badminton, tennis etc) is improved glucose tolerance, weight loss, improved heart function, improved lipid profile, normal gastrointestinal functions and psychological benefits such as improved mood and a healthy sleep pattern. Healthy food and drinking habits are important, and smoking has to be given up.

Hypotensive drugs can be divided into 5 categories:

1. Diuretics

Hypertensive patients seem to handle Na+ just as healthy persons.

Initial administration of diuretics produce a pronounced renal salt and water excretion, which lead to a reduction in ECV, and a fall in systemic blood pressure. The urinary salt and water excretion returns to normal after several days, but the blood pressure remains at the reduced level. This is difficult to explain. Perhaps some diuretics have a direct relaxing effect on vascular smooth muscle in the arterioles or other vessels. 

2. b-adrenergic receptor blockers

b-blockers antagonise competitively the effects of adrenaline and nor-adrenaline on b-adrenergic vasodilatating receptors. The typical non-selective b-adrenergic receptor blocker is propranolol, which is a potent reversible antagonist at both b1-and b2-adrenergic receptors. Propranolol acts on the heart and reduces the chronotropic (reduced heart rate) and inotropic effect (reduced force and cardiac output); the reduced cardiac function is most pronounced during high sympatho-adrenergic activity, such as during exercise or stress, so the drug can release acute cardiac failure. The anti-arrhythmic effect of propranolol is probably due to its local anaesthetic action on cardiac cells including pacemaker cells. The effect of propranolol on hypertension is not clarified, since it seems to increase peripheral vascular resistance slightly. Simultaneously, propranolol reduces the release of renin from the juxtamedullary apparatus. This inhibits aldosterone secretion, and thus reduces the potassium secretion of the distal tubular system. The result is potassium retention, which is further aggravated by b-blockade of receptors on cell membranes, whereby the adrenaline-stimulated Na+-K+ pump is inhibited. Following meals containing carbohydrate and potassium, there is a release of insulin, which stimulates the Na+ - K+ pump, and thus the K+ uptake in cells. Adrenaline also stimulates the Na+- K+pump through activation of b2 - receptors, whereby the plasma-[K+ ] is reduced. The normal effect of insulin is hypoglycaemia, which is compensated by lipolysis and glycogenolysis (with FFA and glucose liberation), by increased sympathoadrenergic activity. Propranolol inhibits lipolysis from adipocytes and glycogenolysis from hepatocytes, myocardial and skeletal muscle cells. This is a problem with diabetics or for patients with reduced glucose tolerance. b-blockade may lead to life threatening hypoglycaemia or a serious rise in blood pressure, if adrenaline release dominates. Propranolol is thus contraindicated in persons with diabetes, sinus bradycardia, partial heart block and congestive heart failure. Propranolol increases airway resistance, which is a hazard to patients with COLD or asthma, because of bronchoconstriction.

Many b-blockers act selectively, but all compounds have effects as described below:

Selective b1-blockers acts on the cardiac b1-receptors and reduces the force of cardiac contraction and thus lowers the blood pressure.

Blockade of b1-adrenergic receptors located on the renin-secreting juxtaglomerular cells reduces the renin release and the blood pressure in persons with renin-dependent hypertension (eg, patients with a high renin level in the plasma from renovascular disease).

Many b-blockers reach the brain tissue through the blood-brain barrier, and others reach the brain cells through the large fenestrae of the circumventricular organs. The CNS-effect is an inhibition of the sympatho-adrenergic output, and beneficial effects on paroxysms of panic and anxiety. The hypotonic CNS-effect is probably dominating, and explains the maintained lowering of blood pressure, although the initial reduction in cardiac output is often only temporary.

3. a1-adrenergic antagonists

This class of drug inhibits the effect mediated through noradrenaline released from sympathetic presynaptic fibres to the postsynaptic a1-receptors and produce vasodilatation. Also a central effect of these compounds (doxazosin, prazosin) may be involved. The hypotensive efficiency of these drugs give rise to the main complication, which is a serious fall in blood pressure following the first dose.


4. Angiotensin Converting Enzyme (ACE) Inhibitors

Angiotensin converting enzyme is found to have the highest activity in the endothelium of the long pulmonary capillaries. Converting enzyme is a kininase II, which convert the decapeptide, angiotensin I, to the vasoconstrictive octapeptide, angiotensin II. ACE inhibitors (captopril, enalapril, and lisinopril) reversibly inhibit converting enzyme and thus act as a vasodilatator of both resistance and capacitance vessels. Angiotensin II is a potent vasoconstrictor, in particular when its concentration in plasma is high. Patients with 100 pg l-1 or more of angiotensin II react beneficial on ACE inhibitors. Also other hypertonics such as diabetic patients reduce their risk of vascular insults by the use of ACE inhibitors for reasons unknown.


5. Calcium-channel blocking agents

Ca2+-antagonists (amlodipine, nifedipine, diltiazem, and verapamil) act as effective vasodilatators, because they relax the smooth muscles of the arterioles. They also inhibit the cardiac contractile force. Ca2+-antagonists inhibits the Ca2+-entry into the cells, because they bind to the proteins of Ca2+-channels in the membrane. The overall effect is beneficial in congestive heart failure, because the vasodilation dimishes TPVR and thus reduces afterload. Hereby, the cardiac output is improved despite cardiac contractile depression. 


6. Future strategy

  ·      Systemic hypertension is the most frequently diagnosed and treated risk factor for the development of atherosclerosis (including ischemic heart disease).  

  ·      A risk factor is a factor showing covariance with atherosclerosis. The remaining risk factors for atherosclerosis are physical inactivity, hypercholesterolaemia, hypertriglyceridaemia, increased LDL concentration, smoking, diabetes, and familiar factors (genes, social inheritance or life style patterns).

  ·      A rational strategy is to control the risk factors for the patients. A successful lowering of arterial blood pressure with a hypotensive drug must not be accompanied by an unrecognised consequential rise in other risk factors.

  ·      Relaxed exercise is an alternative therapeutic strategy to antihypertensive drugs in many cases of essential hypertension. 

  ·      Mild and relaxed exercise has other beneficial effects, namely a consequential reduction of most of the known risk factors for atherosclerosis. 

  ·      Healthy food, exercise and drinking habits are important to hypertonics, and smoking has to be given up. 


2.7 Recent Hypertension Research and Current Topics


1) Controlling Systolic Blood Pressure Prevents All Types Of Strokes
2) Additive Lifestyle Modification Is More Effective Than One Intervention in Reducing Blood Pressure in Both Men and Women With Elevated Blood Pressure
3) ACE Inhibitors Slow the Progression in Both Diabetic and Nondiabetic Chronic Renal Disease
4) Pulse Pressure Predicts Cardiovascular Risk in Older Hypertensive Patients
5) Hypertension Itself and Not the Antihypertensive Agent Affects Sexual Function in Women
6) Moderately Intense Exercise Lowers Stroke Risk in Women