ARTERIAL BLOOD PRESSURE

After studying this chapter you should be able to:

1. Identify cardiac output and the peripheral resistance to blood flow as the major variables determining the dynamically generated arterial blood pressure.

2. Describe the central mechanisms regulating arterial blood pressure including the sensory inputs and the motor outputs via the autonomic nervous system which together make up the baroreceptor reflex.

3. Explain the background to the methods used for routine measurements of arterial blood pressure.

4. Understand the problems inherent in trying to establish what is a normal blood pressure and at what stage a diagnosis of hypertension is established.

5. Explain the major pathological effects of untreated hypertension.

6. Describe the actions of the major classes of drugs available for treating hypertension.

7. Discuss what is meant by hydrostatic pressure in the circulation and explain how it will vary with posture.

Introduction

Pressure developed in the arterial tree depends on the amount of blood being pumped into it, the cardiac output, and the resistance to blood flowing out of the arteries, the peripheral resistance. The resistance of the entire systemic circuit between the aortic valve in the left side of the heart and the right atrium where the blood returns to the heart is called the total peripheral resistance (TPR).

The relationship between the mean arterial blood pressure, cardiac output and resistance can be summarized as follows:

This equation is directly analogous to Ohm’s Law which is concerned with electrical current flow along a wire, i.e. V = I × R. Blood pressure and voltage (V) represent the driving force (potential energy) to move blood or drive current flow. Cardiac output and current flow (I) are equivalent as are the two types of resistance.

A simple model of the arterial circulation is shown in Figure 10.1. Blood pressure can be regulated by changes in either cardiac output or the peripheral resistance.

Fig. 10.1 Simple model of the circulation. Blood pressure in the arterial vessels (the driving force to push blood around the body) depends on the input of blood from the heart (cardiac output) and the resistance to outflow (total peripheral resistance).

Arterial blood pressure provides the driving force to perfuse the tissues of the body with blood. This driving force is dissipated as blood moves round the circulation and there is a continuous fall in pressure between the arteries and the right atrium (see Fig. 9.1). Mean aortic pressure is typically about 95 mm Hg whereas right atrial pressure is about 0–5 mm Hg. Although the output of the heart is phasic, i.e. blood enters the circulatory system during cardiac systole and this ceases when the heart refills during diastole, circulation of blood around all the tissues of the body is continuous. This is driven by the head of pressure maintained in the arterial tree (see page 86). Blood pressure in the arteries is pulsatile but by the time blood reaches the capillaries, where the important functions of the circulatory system take place, the pressure fluctuations have been damped out (see Fig. 9.1).

It is important that arterial pressure is maintained quite constant, as a fall in pressure below a critical level leads to underperfusion of the brain and the subject faints (see Chapter 9). A sustained rise in arterial blood pressure—hypertension—leads to the pathological changes in blood vessels described later in this chapter. Moment to moment fluctuations in arterial blood pressure are minimized by the baroreceptor reflex. This reflex is summarized in Figure 10.2.

Fig. 10.2 The baroreceptor reflex. The response to a fall in arterial blood pressure is an increase in both cardiac output and peripheral resistance that will restore blood pressure.

An outline of a case history of a patient with hypertension is shown in Case 10.1:1.

Case 10.1 Arterial blood pressure: 1

An insurance medical

Mr John Ames is a 45-year-old smoker who is overweight (body mass index 28) but he has been feeling well and has no symptoms of cardiovascular disease. He applied for life insurance cover and was referred for a medical examination. His blood pressure was found to be 188/106 mm Hg. Examination of the cardiovascular system showed no evidence of cardiac disease with no murmurs and with normal pulses all round. His GP arranged a blood test for serum fasting lipids (LDL and HDL cholesterol and triglycerides) and also to check renal function (urea, creatinine and electrolyte concentrations). A urine sample was checked using a dipstick test for glucose and protein. A renal ultrasound test to assess kidney size was arranged at the local hospital.

While waiting for the results of these tests to return the GP insisted that John should come to the surgery to have his blood pressure measured twice more by the practice nurse in the coming 10 days. The blood, urine and ultrasound tests all provided normal results but John’s blood pressure was still high on the subsequent checks and the GP told him he had essential hypertension. A thiazide diuretic was prescribed. This history raises the following questions.

1. John was told he had essential hypertension. What does this mean? At what level of blood pressure elevation should therapy be considered?

2. Why was it important to check John’s blood lipid levels?

3. What was the reason behind the repeated blood pressure measurements?

4. Why was John’s renal function checked?

5. What does body mass index mean?

Aspects of the answers to these questions are to be found in the text of this chapter and in Box 10.1.

The factors determining cardiac output have been discussed in Chapter 4. The essential features are that the heart has an intrinsic contractile rate which can be modified by the parasympathetic (vagus) nerve to slow the heart or by the sympathetic nerves to increase heart rate. The force of contraction of the heart and, therefore, the stroke volume is determined by a combination of preload effects (blood volume, venous return, venous tone), contractility effects (changes in myocyte [Ca⁺⁺] produced physiologically by sympathetic nerve stimulation) and afterload effects (mainly opposition to opening the aortic valve produced by the arterial blood pressure).

The factors determining peripheral blood vessel resistance to flow have been discussed in Chapter 9. Some of the mechanisms (metabolite, endothelial and local hormone effects) ensure an appropriate distribution of flow within tissues to match the local metabolic activity. Adjustment of the overall resistance to maintain arterial blood pressure at a relatively constant level is achieved by the autonomic nerve supply to peripheral blood vessels. This has the fundamental characteristics that it is sympathetic in origin, using noradrenaline (norepinephrine) as the main neurotransmitter which, acting primarily through α₁-receptors, leads to vasoconstriction (see Chapter 9). Although there are parts of the circulation where one or other of these characteristics does not apply, these are very limited and specialized aspects of vascular control and are not major factors determining the total peripheral resistance.

In order to link all these components together we need a baroreceptor mechanism to continuously provide central control mechanisms in the brain with information about the current arterial blood pressure.

Interesting facts

In 1733 the Englishman, the Reverend Stephen Hales, made the first successful measurement of blood pressure by inserting a long glass tube into the carotid artery and jugular vein of a horse. Blood in the arterial cannula rose 2.92 metres up the tube, but in the venous cannula it was only 0.5 metres.

Arterial baroreceptors

Baroreceptors are actually modified nerve endings buried in the blood vessel wall. An increase in pressure within the vessel stretches the blood vessel wall and therefore distorts the nerve endings. This leads to the opening of ion channels and the generation of action potentials in the baroreceptor nerves. If the blood vessel is experimentally prevented from expanding in response to a change in internal pressure, then there is no change in action potential number. This demonstrates that the baroreceptor does not directly monitor pressure as such but rather pressure is sensed indirectly as stretch produced in blood vessel walls.

Anatomical location of baroreceptors

The location of the main arterial baroreceptors is shown in Figure 10.3.

Fig. 10.3 Location of major arterial baroreceptors.

The carotid sinus is a thin-walled dilatation of the internal carotid artery which occurs just after the bifurcation of the common carotid artery into the internal and external carotid arteries. The carotid sinus baroreceptor is a bundle of nerve fibres which is a part of the glossopharygeal (IX) cranial nerve.

The aortic arch baroreceptor is a part of the vagus (X) cranial nerve and the nerve endings are distributed in the wall of the aortic arch.

Information from these two groups of baroreceptors enters the brain at the level of the medulla.

Central control of the cardiovascular system

The view that the cardiovascular system is regulated from a ‘vasomotor centre’ located in the medulla is now obsolete. This concept implies an anatomically distinct part of the brain which could be demonstrated in a dissection room. In practice cardiovascular control involves interaction between diffuse parts of the medulla, hypothalamus, cerebral cortex and cerebellum.

The initial processing of information from the baroreceptors occurs in the nucleus tractus solitarius (NTS) in the medulla. The NTS has connections to the regions of the medulla which organize the outflow to the two divisions of the autonomic nervous system. The cell bodies of the preganglionic parasympathetic nerves, which slow heart rate, are located in the nucleus ambiguus and the dorsal motor nucleus. There are also neural connections from the NTS to the rostral ventrolateral medulla, a region of the brainstem controlling the sympathetic outflow to the heart (increases rate) and to the peripheral blood vessels (mainly leading to vasoconstriction). Figure 10.4 summarizes the main pathways in the medulla involved in the control of arterial blood pressure.

Fig. 10.4 Blood pressure regulation by medulla. Major pathways in medulla which are concerned with blood pressure regulation. CVLM = caudal ventrolateral medulla; NA = nucleus ambiguus; NTS = nucleus tractus solitarius; RVLM = rostral ventrolateral medulla.

The hypothalamus functions effectively as the site within the brain which contains information about the ‘set point’ for arterial blood pressure i.e. what the pressure should normally be held at. The hypothalamus has a number of regions involved in cardiovascular control. The hypothalamic depressor area receives an input from the NTS. It is therefore informed about the arterial blood pressure and plays a very significant role in the baroreceptor reflex. The defence area of the hypothalamus plays a part in the cardiovascular responses to acute stress. The response to stress is an increase in heart rate and sympathetically mediated vasoconstriction particularly in the skin, the splanchnic (gut and liver) and the kidney circulations. An acute rise in blood pressure occurs in response to stress which means that the normal baroreceptor reflex, which keeps blood pressure constant, has been overridden. The brain regions involved in this include the amygdala, part of the limbic system. The series of responses to acute stress, which include changes in blood pressure, has been given various names including the term ‘alerting response’. The cardiovascular responses are reversed quite quickly when the perceived threat is removed.

A further function of the hypothalamus in vascular control relates to the fact that the temperature regulating area in the anterior hypothalamus controls the changes in skin blood flow which are part of the response to changes in body temperature.

The cerebellum is involved in the coordination of muscle movement in exercise and is also involved in the circulatory responses to exercise. Aspects of this are discussed in Chapter 13.

The baroreceptor reflex

A flow chart summarizing the baroreceptor reflex for the regulation of arterial blood pressure is shown in Figure 10.2. The responses to a fall in blood pressure are illustrated. The reflex response is an increase in heart rate, an increase in the force of cardiac contraction and an increase in peripheral vasoconstriction, all of which will help to restore blood pressure to normal levels. It has been said that regulation of heart rate is the primary role of the baroreceptor reflex and that responses leading to vasoconstriction and venoconstriction are of secondary importance.

The functional characteristics of the carotid sinus and aortic arch baroreceptors are essentially similar. Both consist of a mixture of large myelinated nerve fibres (A fibres) and a greater number of small, unmyelinated C fibres. The A fibres have a lower threshold response (30–90 mm Hg) than the C fibres (70–140 mm Hg). Thus, at normal pressures, A fibres are all stimulated to generate action potentials but only about a quarter of the C fibres are active. The A fibres reach a maximum firing rate before the C fibres. A generalization would therefore be that the myelinated A fibres are most important at normal pressure ranges but the C fibres become increasingly activated as pressure rises above the normal level. The arterial baroreceptors provide an input to the brain relaying pulse pressure, i.e. rate of change of pressure, as well as mean arterial pressure.

Baroreceptor reflex resetting occurs during the long-term rises in blood pressure known as hypertension and also during the changes in blood pressure which occur with increasing age. The site of these adaptive changes is in the central control mechanisms. The changes in baroreceptor function are a consequence of raised blood pressure rather than a primary cause of hypertension. Sensitivity of the baroreceptor mechanism may decrease when there are changes in the arterial wall compliance which sometimes occur as a consequence of atherosclerotic changes (see Chapter 8).

In humans, circulatory control mechanisms are dominated by the baroreceptor reflex but there are also other reflex responses which contribute to overall control.