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CHAPTER 11 Antihypertensive Agents 175

(see Chapter 17) constricts and nitric oxide (see Chapter 19) B. Renal Response to Decreased Blood Pressure
dilates blood vessels. By controlling blood volume, the kidney is primarily responsible
Blood pressure in a hypertensive patient is controlled by the for long-term blood pressure control. A reduction in renal perfu-
same mechanisms that are operative in normotensive subjects. sion pressure causes intrarenal redistribution of blood flow and
Regulation of blood pressure in hypertensive patients differs from increased reabsorption of salt and water. In addition, decreased
healthy patients in that the baroreceptors and the renal blood pressure in renal arterioles as well as sympathetic neural activ-
volume-pressure control systems appear to be “set” at a higher ity (via β adrenoceptors) stimulates production of renin, which
level of blood pressure. All antihypertensive drugs act by interfer- increases production of angiotensin II (see Figure 11–1 and
ing with these normal mechanisms, which are reviewed below. Chapter 17). Angiotensin II causes (1) direct constriction of
resistance vessels and (2) stimulation of aldosterone synthesis in
A. Postural Baroreflex the adrenal cortex, which increases renal sodium absorption and
Baroreflexes are responsible for rapid, moment-to-moment adjust- intravascular blood volume. Vasopressin released from the pos-
ments in blood pressure, such as in transition from a reclining to terior pituitary gland also plays a role in maintenance of blood
an upright posture (Figure 11–2). Central sympathetic neurons pressure through its ability to regulate water reabsorption by the
arising from the vasomotor area of the medulla are tonically kidney (see Chapters 15 and 17).
active. Carotid baroreceptors are stimulated by the stretch of the
vessel walls brought about by the internal pressure (arterial blood
pressure). Baroreceptor activation inhibits central sympathetic ■ BASIC PHARMACOLOGY OF
discharge. Conversely, reduction in stretch results in a reduction ANTIHYPERTENSIVE AGENTS
in baroreceptor activity. Thus, in the case of a transition to upright
posture, baroreceptors sense the reduction in arterial pressure
that results from pooling of blood in the veins below the level All antihypertensive agents act at one or more of the four ana-
of the heart as reduced wall stretch, and sympathetic discharge tomic control sites depicted in Figure 11–1 and produce their
is disinhibited. The reflex increase in sympathetic outflow acts effects by interfering with normal mechanisms of blood pressure
through nerve endings to increase peripheral vascular resistance regulation. A useful classification of these agents categorizes
(constriction of arterioles) and cardiac output (direct stimula- them according to the principal regulatory site or mechanism on
tion of the heart and constriction of capacitance vessels, which which they act (Figure 11–3). Because of their common mecha-
increases venous return to the heart), thereby restoring normal nisms of action, drugs within each category tend to produce
blood pressure. The same baroreflex acts in response to any event a similar spectrum of toxicities. The categories include the
that lowers arterial pressure, including a primary reduction in following:
peripheral vascular resistance (eg, caused by a vasodilating agent) 1. Diuretics, which lower blood pressure by depleting the body of
or a reduction in intravascular volume (eg, due to hemorrhage or sodium and reducing blood volume and perhaps by other
to loss of salt and water via the kidney). mechanisms.

IC
2. Nucleus of the tractus solitarius
Brain- CP Sensory fiber
stem 1. Baroreceptor
in carotid sinus
Inhibitory interneurons
X
XI
XII Arterial blood pressure
Vessel wall
3. Vasomotor
center
Motor fibers

5 6
Spinal
cord
4. Autonomic 5. Sympathetic
ganglion nerve ending 6. α or β
receptor
FIGURE 11–2 Baroreceptor reflex arc. CP, cerebellar peduncle; IC, inferior colliculus.