Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
The notion that sympathetic fibers are found on the vascular wall and when stimulated cause vasoconstriction was proposed in 1840. The activity of these fibers is one of the components that control peripheral vascular resistance. Hyperactivity of the sympathetic nervous system is well described not only in hypertensive patients, but also in subjects at risk of progressing to hypertension, namely normotensive individuals with a family history of hypertension and those with white-coat hypertension.
The high adrenergic drive in hypertensive patients is attributed to: (1) enhanced spillover rate from neuroeffective junctions and the resulting augmented norepinephrine secretion from sympathetic nerve terminals ; (2) impaired vagal tone and reduced parasympathetic activity ; and (3) increased central adrenergic drive and peripheral sympathetic nerve traffic to the skeletal muscle circulation.
In patients with sustained hypertension, the high sympathetic drive is demonstrated in all subgroups of the hypertensive population: males, females, diabetics, and those with metabolic syndrome, young and old. Furthermore, the degree of the sympathetic drive has a positive correlation with the severity of hypertension and with hypertensive complications, especially left ventricular hypertrophy.
The alpha adrenergic receptors (α-ARs) are activated by the catecholamines epinephrine and norepinephrine. Alpha and beta ARs are divided into subclasses: α 1 -AR–α 1 A-AR, α 1 B-AR, and α 1 D-AR; α 2 -AR–α 2 A-AR, α 2 B-AR, and α 2 C-AR; and β-AR–β 1 -AR, β 2 -AR, and β 3 -AR. Most of the cells in the human body express at least one of the nine AR subclasses. The α-ARs are composed of α 1 -ARs and α 2 -ARs. The α 1 -ARs are postsynaptic. Their activation results in norepinephrine release and vasoconstriction. The α 2 -ARs are located in the presynaptic and postsynaptic areas. When located presynaptically, they inhibit norepinephrine release, whereas when located postsynaptically, they increase norepinephrine release and mediate vasoconstriction and venoconstriction.
α 1 -ARs are expressed in various organs, including the brain, heart, liver, kidney, prostate, spleen, and blood vessels. Activation of the α 1 -AR mediates modulation of neurotransmission as well as regulation of the cardiovascular system and metabolism.
All α 1 -ARs play a role in the regulation of vascular tone. However, the most major contribution to vascular tone is made by the α 1 A-AR and α 1 D-AR subclasses; α 1 A-ARs are located in distributing arteries (the mesenteric and renal arteries) and α 1 D-ARs are located in large conducting arteries (the aorta, the carotid), as well in the coronary arteries. The expression of the α 1 B-AR subclass is minor in the vascular structure, but is increased in older individuals (>65 years).
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here