Hypertension

Hypertension, commonly known as high blood pressure, is when the systolic blood pressure is greater than 140 mm Hg or the diastolic blood pressure is greater than 90 mm Hg.  Hypertension is very common among adults with the CDC reporting that 47% of U.S. adults have hypertension (the definition of hypertension in this statistic is a systolic blood pressure > 130 mm Hg or diastolic blood pressure greater than 80 mm Hg).  Hypertension is generally asymptomatic but is a risk factor for the development of heart disease and stroke.  Appropriate treatment of hypertension reduces the risk of developing heart disease including heart failure and coronary artery disease, kidney disease, and stroke.  

Hypertension is caused by increased peripheral vascular resistance. Increased peripheral vascular resistance may result from increased smooth muscle tone of arterioles or from decreased elasticity of blood vessels.  

Risk factors for hypertension include age, race, obesity, diabetes, and environmental factors including smoking.

Physiology

Blood pressure is regulated through the renin-angiotensin-aldosterone system as well as from feedback from baroreceptors.  

Renin-Angiotensin-Aldosterone System

Effects from the renin-angiotensin-aldosterone system is the mainstay for long-term control of blood pressure.  The kidneys have baroreceptors that respond to arterial pressure.  Changes in arterial pressure at the kidney results in alteration of the rate of secretion of renin and changes in the glomerular filtration rate.  

Renin is an enzyme that when released converts angiotensinogen to angiotensin I. Angiotensin I is then converted to angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II is a protein that has multiple effects, primarily causing vasoconstriction of arterioles and veins including arterioles of the kidney.  Constriction of renal arterioles decreases GFR, which ultimately leads to retention of fluid and sodium and increases blood volume.   

Angiotensin II also stimulates aldosterone secretion. Aldosterone increases sodium retention in the kidneys, which ultimately causes increased blood volume and higher blood pressure.  

Baroreceptor System

Baroreceptors are blood pressure sensing neurons. The primary baroreceptors are located in the carotid artery and the aortic arch.  Changes in blood pressure alter the signals sent from the baroreceptors to the spinal cord.  Increases in blood pressure signal to decrease sympathetic outflow, which results in decreased cardiac output from less stimulation of beta-1 receptors.  Smooth muscle relaxation also occurs from decreased stimulation of alpha-1 receptors, which causes decreased peripheral vascular resistance and decreased return of blood to the heart.  

Treatment Strategies

Lifestyle modification should be a tenant of strategy for reducing blood pressure in order to minimize the need for medication management.  Lifestyle modification alone is unlikely to be successful for many patients, so medication management becomes necessary.  

Diuretics

Diuretics work by decreasing the blood volume, which lowers blood pressure.  There are several classes of diuretics. 

Thiazide Diuretics

Thiazide diuretics decrease reabsorption of sodium and chloride in the distal convoluted tubule of the kidney, which decreases blood volume and lowers blood pressure. Over time, blood volume normalizes but blood pressure effects remain from decreased peripheral vascular resistance from arteriolar smooth muscle relaxation. These are potassium wasting diuretics.

Loop Diuretics

Loop diuretics act by blocking sodium and chloride reabsorption in the loop of Henle by blocking the Sodium-Potassium-Chloride cotransporter.  This action results in retention of sodium, chloride and water in the tubule.  Loop diuretics are not generally used alone to treat hypertension. Loop diuretics are potassium wasting.

Potassium Sparing Diuretics

Potassium sparing diuretics include aldosterone antagonists and sodium transport channel blockers (triamterene and amiloride). Aldosterone antagonists cause decreased stimulation of sodium-potassium exchange sites in the collecting tubules, which results in less sodium retention and decreased fluid retention. Triamterene and amiloride affect the process more directly than aldosterone antagonists.  These drugs are potassium sparing.  

Renal Tubule - Primary sites of action of diuretics.

Beta Blockers

Beta blockers primarily decrease cardiac output by decreasing contractility and slowing heart rate, which results in lower blood pressure. Beta blockers also decrease renin release in the kidneys, which lowers blood pressure through the renin-angiotensin-aldosterone system.

ACE Inhibitors

Angiotensin converting enzyme (ACE) inhibitors inhibit the conversion of angiotensin I to angiotensin II, which results in lower blood pressure through the renin-angiotensin-aldosterone system.  Additionally, ACE inhibitors decrease the breakdown of bradykinin, which is also performed by ACE.  Bradykinin is responsible for increasing production of nitric oxide and prostacyclin, which are both vasodilators.  

Angiotensin II Receptor Blockers

Angiotensin II Receptor Blockers (ARBs) block AT1 receptors, which are activated by Angiotensin II.  ARBs have similar effects as ACE inhibitors.  ARBs do not increase bradykinin levels.  

Renin Inhibitors

Renin inhibitors also work on the renin-angiotensin-aldosterone system to lower blood pressure by decreasing production of angiotensin II.  

Renin-Angiotensin-Aldosterone System - Sites of inhibition by medication classes affecting the renin-angiotensin-aldosterone system

Calcium Channel Blockers

Calcium channel blockers block inward movement of calcium into muscle cells, which decreases muscle tone of arterioles, which causes decreased peripheral vascular resistance.  Calcium channel blockers are also negative inotropes and chronotropes. Blood pressure changes are primarily through their effects on peripheral vascular resistance.

Alpha Blockers

Alpha blockers decrease peripheral vascular resistance due to the blockage of alpha-1 receptors, which increase vascular tone when stimulated.

Central Adrenergic Drugs

Clonidine and methyldopa act centrally on alpha-2 receptors, which decreases sympathetic outflow. Decreased sympathetic outflow results in decreased peripheral vascular resistance and lowered blood pressure.

Vasodilators

Vasodilators are direct smooth muscle relaxers that act on smooth muscles of arteries and arterioles to lower blood pressure. Examples of these medications are hydralazine and minoxidil.