pressure greater than 96 torr. If the diastolic value exceeds 115 torr, then the afflicted
individual has severe hypertension.
In hypertension, the prolonged elevation of pressure against the arterial walls either
damages the lining of the artery, promoting atherosclerosis and eventual partial or total
blockage of the artery at the point or zone of damage, or causes the arterial wall to rup-
ture. Not surprisingly, there are many long-term secondary complications arising from
hypertension: coronary artery atherosclerosis (producing angina pectoris which may
progress to a myocardial infarction [heart attack] that may or may not be complicated
by cardiac arrhythmias), cerebral artery atherosclerosis (producing transient ischemic
attacks which may progress to a cerebral infarction [stroke] that may or may not be
complicated by seizures), peripheral artery atherosclerosis (producing intermittent
claudication—lower leg calf pain during physical exertion), renal artery atheroscle-
rosis (producing decreased renal function and ultimately kidney failure), heart failure
(mechanical failure of the heart, either because it is pumping against a high peripheral
resistance or because the muscles of the heart are damaged by a myocardial infarction),
or cerebral haemorrhage (from rupture of a blood vessel within the brain).
Since optimal blood pressure is crucial to the health of the organism as a whole, it is
also not surprising that there are many control systems within the body to influence and
adjust the blood pressure. Components of both the peripheral and central nervous
systems, as well as the hormonal systems of the kidney, heart, and peripheral vascular
network, all work in concert to continuously adjust blood pressure on a short and inter-
mediate timeframe basis. Arising from this complexity is the availability of numerous
druggable targets that may be exploited for antihypertensive drug design. These include
one or more of the following four general mechanistic targets:
- Neurotransmitter receptorsas messenger targets (e.g., adrenergic drugs such as
β-blockers, chapter 4) - Hormone receptorsas messenger targets (e.g., renin–angiotensin system drugs,
section 5.21) - Endogenous cellular structuresas nonmessenger targets (e.g., membrane targets
such as Ca^2 +ion channels, section 7.1) and - Endogenous macromoleculesas nonmessenger targets (e.g., carbonic anhydrase
inhibitors or other agents as diuretics, chapter 8)
In keeping with these four mechanistic classes of antihypertensives, the clinically use-
ful agents for hypertension can be grouped into four corresponding major categories:
- Sympathoplegic agents: lower blood pressure by inhibiting cardiac function,
increasing venous pooling in capacitance vessels (rather than in arterial resistance
vessels), and reducing peripheral vascular resistance (e.g.,β-adrenergic antagonists
such as propranolol (4.63),α-agonists such as clonidine (4.42), and biogenic amine
depletories such as reserpine (3.1)) - Hormonal agentsthat inhibit the production or action of angiotensin: reduce periph-
eral vascular resistance and possibly blood volume (e.g., ACE inhibitors such as
enalapril (5.137), AT 1 antagonists); other hormones that influence blood pressure
could also be targeted
HORMONES AND THEIR RECEPTORS 379