β-Blockers, Central Sympathetic Agents, and Direct Vasodilators

The sympathetic nervous system, along with the renin-angiotensin aldosterone system, is a major cardiovascular regulatory system, and sympathetic activation is closely related to the development and progression of hypertension. β-blockers exert antihypertensive effects by blocking β1-adrenoceptors in the heart and the kidneys, decreasing cardiac output and suppressing renin secretion, respectively. Although β-blockers are not first-line agents for the treatment of hypertension, they are used as the primary therapeutics for hypertensive patients with ischemic heart disease and heart failure because of the abundant evidence for secondary prevention and improvement of mortality. Central sympathetic agents cross the blood-brain barrier and stimulate α2-adrenoceptors and imidazoline 1 receptors in the cardiovascular center in the brain, such as the nucleus tractus solitarius and the rostral ventrolateral medulla, suppressing peripheral sympathetic nerve activity and thereby exerting an antihypertensive effect. Central sympathetic agents are used in combination with other antihypertensive drugs for treatment-resistant hypertension, although they are not recommended as first- or second-line agents because of their relatively high frequency of side effects and lack of evidence for improvement of mortality. Methyldopa, one of the central sympathetic agents, is used mainly to treat hypertension in pregnant women. Direct vasodilators act directly on vascular smooth muscle to dilate blood vessels. Hydralazine, one of the direct vasodilators, is used in hypertensive emergencies because it is fast-acting. In addition to standard hypertension treatment, hydralazine is used in combination with diuretics, β-blockers, and sympathomimetics to prevent compensatory sympathetic activation that induces a phenomenon called pseudotolerance.