Page 188 - Basic _ Clinical Pharmacology ( PDFDrive )

174 SECTION III Cardiovascular-Renal Drugs

TABLE 11–1 Classification of hypertension on the potassium or calcium intake) as contributing to the development
basis of blood pressure. of hypertension. Increase in blood pressure with aging does not
occur in populations with low daily sodium intake. Patients with
Systolic/Diastolic Pressure labile hypertension appear more likely than normal controls to
(mm Hg) Category
have blood pressure elevations after salt loading.
< 120/80 Normal The heritability of essential hypertension is estimated to be
120–139/80–89 Prehypertension about 30%. Mutations in several genes have been linked to vari-
ous rare causes of hypertension. Functional variations of the genes
≥ 140/90 Hypertension
for angiotensinogen, angiotensin-converting enzyme (ACE), the
140–159/90–99 Stage 1
angiotensin II receptor, the β adrenoceptor, α adducin (a cyto-
2
≥ 160/100 Stage 2 skeletal protein), and others appear to contribute to some cases of
From the Joint National Committee on prevention, detection, evaluation, and treatment essential hypertension.
of high blood pressure. JAMA 2003;289:2560.
Normal Regulation of Blood Pressure
140/90 mm Hg) increases the risk of eventual end-organ damage. According to the hydraulic equation, arterial blood pressure (BP)
Starting at 115/75 mm Hg, cardiovascular disease risk doubles is directly proportionate to the product of the blood flow (cardiac
with each increment of 20/10 mm Hg throughout the blood pres- output, CO) and the resistance to passage of blood through
sure range. Both systolic hypertension and diastolic hypertension precapillary arterioles (peripheral vascular resistance, PVR):
are associated with end-organ damage; so-called isolated systolic
hypertension is not benign. The risks—and therefore the urgency BP = CO × PVR
of instituting therapy—increase in proportion to the magnitude Physiologically, in both normal and hypertensive individuals,
of blood pressure elevation. The risk of end-organ damage at any blood pressure is maintained by moment-to-moment regula-
level of blood pressure or age is greater in African Americans and tion of cardiac output and peripheral vascular resistance, exerted
relatively less in premenopausal women than in men. Other posi- at three anatomic sites (Figure 11–1): arterioles, postcapillary
tive risk factors include smoking; metabolic syndrome, including venules (capacitance vessels), and heart. A fourth anatomic control
obesity, dyslipidemia, and diabetes; manifestations of end-organ site, the kidney, contributes to maintenance of blood pressure by
damage at the time of diagnosis; and a family history of cardio- regulating the volume of intravascular fluid. Baroreflexes, medi-
vascular disease. ated by autonomic nerves, act in combination with humoral
It should be noted that the diagnosis of hypertension depends mechanisms, including the renin-angiotensin-aldosterone sys-
on measurement of blood pressure and not on symptoms reported tem, to coordinate function at these four control sites and to
by the patient. In fact, hypertension is usually asymptomatic until maintain normal blood pressure. Finally, local release of vasoac-
overt end-organ damage is imminent or has already occurred. tive substances from vascular endothelium may also be involved
in the regulation of vascular resistance. For example, endothelin-1
Etiology of Hypertension
A specific cause of hypertension can be established in only 10–15% 2. Capacitance
of patients. Patients in whom no specific cause of hypertension can Venules 3. Pump output
be found are said to have essential or primary hypertension. Patients Heart
with a specific etiology are said to have secondary hypertension. It is
important to consider specific causes in each case, however, because
some of them are amenable to definitive surgical treatment: renal CNS–
artery constriction, coarctation of the aorta, pheochromocytoma, Sympathetic nerves
Cushing’s disease, and primary aldosteronism.
In most cases, elevated blood pressure is associated with an 4. Volume
overall increase in resistance to flow of blood through arterioles, 1. Resistance Kidneys
whereas cardiac output is usually normal. Meticulous investiga- Arterioles
tion of autonomic nervous system function, baroreceptor reflexes,
the renin-angiotensin-aldosterone system, and the kidney has Renin
failed to identify a single abnormality as the cause of increased
peripheral vascular resistance in essential hypertension. It appears,
therefore, that elevated blood pressure is usually caused by a Aldosterone Angiotensin
combination of several (multifactorial) abnormalities. Epidemio-
logic evidence points to genetic factors, psychological stress, and
environmental and dietary factors (increased salt and decreased FIGURE 11–1 Anatomic sites of blood pressure control.