In most cases, elevated blood pressure is associated with an overall increase in resistance to flow of blood through arterioles, whereas cardiac output is usually normal. Meticulous investigation of autonomic nervous system function, baroreceptor reflexes, the renin-angiotensin-aldosterone system, and the kidney has 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 combination of several (multifactorial) abnormalities. Epidemiologic evidence points to genetic factors, psychological stress, and environmental and dietary factors (increased salt and decreased (see Chapter 17) constricts and nitric oxide (see Chapter 19) dilates blood vessels.
4. Volume       Kidneys 2. Capacitance Venules 1. Resistance Arterioles 3. Pump output    Heart Aldosterone Angiotensin Renin CNS– Sympathetic nerves FIGURE 11–1 Anatomic sites of blood pressure control. potassium or calcium intake) as contributing to the development of hypertension. Increase in blood pressure with aging does not occur in populations with low daily sodium intake. Patients with labile hypertension appear more likely than normal controls to have blood pressure elevations after salt loading. The heritability of essential hypertension is estimated to be about 30%. Mutations in several genes have been linked to vari-ous rare causes of hypertension. Functional variations of the genes for angiotensinogen, angiotensin-converting enzyme (ACE), the angiotensin II receptor, the β2 adrenoceptor, α adducin (a cyto-skeletal protein), and others appear to contribute to some cases of essential hypertension. Normal Regulation of Blood Pressure According to the hydraulic equation, arterial blood pressure (BP) is directly proportionate to the product of the blood flow (cardiac output, CO) and the resistance to passage of blood through precapillary arterioles (peripheral vascular resistance, PVR): BP = CO × PVR Physiologically, in both normal and hypertensive individuals, blood pressure is maintained by moment-to-moment regula-tion of cardiac output and peripheral vascular resistance, exerted at three anatomic sites (Figure 11–1): arterioles, postcapillary venules (capacitance vessels), and heart. A fourth anatomic control site, the kidney, contributes to maintenance of blood pressure by regulating the volume of intravascular fluid. Baroreflexes, medi-ated by autonomic nerves, act in combination with humoral mechanisms, including the renin-angiotensin-aldosterone sys-tem, to coordinate function at these four control sites and to maintain normal blood pressure. Finally, local release of vasoac-tive substances from vascular endothelium may also be involved in the regulation of vascular resistance. For example, endothelin-1
Blood pressure in a hypertensive patient is controlled by the same mechanisms that are operative in normotensive subjects. Regulation of blood pressure in hypertensive patients differs from healthy patients in that the baroreceptors and the renal blood volume-pressure control systems appear to be “set” at a higher level of blood pressure. All antihypertensive drugs act by interfering with these normal mechanisms, which are reviewed below.
A. Postural Baroreflex