A Textbook of Clinical Pharmacology and Therapeutics

Cardiac output may be increased in children or young
adults during the earliest stages of essential hypertension, but
by the time hypertension is established in middle life the pre-
dominant haemodynamic abnormality is an elevated periph-
eral vascular resistance. With ageing, elastic fibres in the aorta
and conduit arteries are replaced by less compliant collagen
causing arterial stiffening and systolic hypertension, which is
common in the elderly.
The kidney plays a key role in the control of blood pressure
and in the pathogenesis of hypertension. Excretion of salt and
water controls intravascular volume. Secretion of renin influ-
ences vascular tone and electrolyte balance via activation of the
renin–angiotensin–aldosterone system. Renal disease (vascular,

parenchymal or obstructive) is a cause of arterial hypertension.

Conversely, severe hypertension causes glomerular sclerosis,

manifested clinically by proteinuria and reduced glomerular fil-

tration, leading to a vicious circle of worsening blood pressure

and progressive renal impairment. Renal cross-transplantation

experiments in several animal models of hypertension, as well

as observations following therapeutic renal transplantation in

humans, both point to the importance of the kidney in the

pathogenesis of hypertension.

The sympathetic nervous system is also important in the

control of blood pressure, providing background αreceptor-

mediated vasoconstrictor tone and βreceptor-mediated cardiac

stimulation. Sympathetic activity varies rapidly to adjust for

changes in cardiovascular demand with alterations in posture

and physical activity. It is also activated by emotional states

such as anxiety, and this can result in ‘white-coat’ hyperten-

sion. A vasoconstrictor peptide, endothelin, released by the

endothelium contributes to vasoconstrictor tone. Conversely,

endothelium-derived nitric oxide provides background active

vasodilator tone.

Cardiovascular drugs work by augmenting or inhibiting

these processes, see Figure 28.3. The main such drugs for treat-

ing hypertension can usefully be grouped as:

Aangiotensin-converting enzyme inhibitors (ACEI) and

angiotensin AT 1 receptor antagonists (sartans);

B beta-adrenoceptor antagonists;

C calcium channel antagonists;

Ddiuretics.

186 HYPERTENSION

Heart

Peripheral resistance Kidneys

Figure 28.2:Arterial blood pressure is controlled by the force of
contraction of the heart and the peripheral resistance (resistances
in parallel though various vascular beds). The fullness of the
circulation is controlled by the kidneys, which play a critical role
in essential hypertension.

Sympathetic ganglia

Adrenal cortex

Heart

β-Blockers

(‘B’ drugs)

Vasomotor centre

α 2 -Adrenoceptor agonists

(e.g. clonidine)

Imidazoline receptor agonists

(e.g. moxonidine)

Vascular smooth muscle

ACE inhibitors

Angiotensin receptor blockers

Calcium channel blockers (‘C’ drugs)

Diuretics (‘D’ drugs)

α 1 -Blockers (e.g. doxazosin)

ACE inhibitors

Angiotensin receptors blockers

Mineralocorticoid antagonists

Juxtaglomerular cells

β-blockers (‘B’ drugs)

Renin inhibitors

Kidney tubules

Diuretics (‘D’ drugs)

ACE inhibitors

Angiotensin

receptor blockers

(‘A’ drugs)

(‘A’ drugs)

‘A’ drugs

Figure 28.3:Classes of

antihypertensive drugs and their

sites of action.