Elevated blood pressure (BP) is the product of increased cardiac output (CO) and peripheral vascular resistance (PVR). Increased CO may result from increased fluid volume from excess sodium intake or renal sodium retention, stimulation of the renin-angiotensin-aldosterone system (RAAS), or activation of the sympathetic nervous system (SNS). Functional constriction or structural hypertrophy of the vasculature increases PVR. Both result from excess stimulation of the RAAS, SNS overactivity, genetic alterations of cell membranes, or endothelial-derived factors.

Recommendations for treating hypertension are based on the 2017 American College of Cardiology /American Heart Association (ACC/AHA) Hypertension Guidelines. Hypertension is diagnosed from the average of two or more BP measurements. Normal BP is less than 120/80 mmHg. Elevated BP is 120-129/<80 mmHg. Stage 1 hypertension is classified as 130-139/80-89 mmHg. Stage 2 hypertension is considered at pressures greater than 140/90 mmHg. The BP goal for most patients with hypertension is less than 130/80 mmHg.

Patients with elevated and Stage 1 hypertension with an atherosclerotic cardiovascular disease (ASCVD) 10-year risk less than 10% should be managed through nonpharmacologic regulation of BP which includes weight loss with a heart-healthy diet, dietary sodium restriction and potassium supplementation, increased physical activity, and limited alcohol consumption. If these patients have an ASCVD 10-year risk greater than 10% or clinical CVD, antihypertensive drug therapy should also be initiated. Patients with Stage 2 hypertension will most likely require two or more medications to reach the target BP.

Angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazides reduce mortality in patients with hypertension and are considered first-line therapies. As a group, African American patients show a smaller response in BP reduction to ACEIs or ARBs than Caucasian patients. Therefore, patients that self-identify as Black or African American should be preferentially placed on a CCB or thiazide. If microalbuminuria is present (urine albumin:creatinine ≥300 mg/g), an ACEI or ARB should be considered.

1. ACEIs (lisinopril, enalapril, captopril, etc.) decrease angiotensin II formation and subsequent aldosterone synthesis, thereby reducing vasoconstriction and sodium and water retention. ARBs (losartan, valsartan, telmisartan, etc.) are similar to ACEIs.  While ACEI’s block formation of angiotensin II, ARBs block the effects of angiotensin II by antagonizing AT1 receptors. ARBs are recommended for patients that are unable to tolerate ACEIs, usually due to dry cough or rare incidences of angioedema. ARBs should not be initiated in patients with a history of angioedema, hypotension, hyperkalemia, or renal insufficiency with ACEIs

2. CCBs reduce calcium ion influx during depolarization of cardiac and/or vascular smooth muscle leading to muscle relaxation.  Non-dihydropyridine CCBs (diltiazem, verapamil) are more cardioselective, have negative inotropic effects, and decrease CO.  On the other hand, the dihydropyridine CCBs (amlodipine, nicardipine, nifedipine, etc.) act mostly on vascular smooth muscle to decrease PVR.

3. Thiazides (hydrochlorothiazide, chlorthalidone, etc.) inhibit sodium reabsorption in the renal distal tubules causing increased excretion of sodium, water, potassium and hydrogen ions. While their diuretic effect is not as potent as loop diuretics, thiazides exhibit significant antihypertensive activity and have a longer duration of action. Loop diuretics, however, should replace thiazides in patients with impaired kidney function and a reduced estimated glomerular filtration rate.


Comorbidities drive therapeutic decision-making. Beta-blockers are not recommended as monotherapy for the treatment of hypertension and should only be considered if heart failure or other comorbidities are also present. Dihydropyridine CCBs should be avoided in patients with heart failure. Alpha-blockers are not recommended due to orthostasis risk unless the patient has benign prostatic hyperplasia.

1. Resistant hypertension

This occurs when BP is not at goal while taking a 3-drug complementary regimen which typically includes a longer-acting thiazide like chlorthalidone, ACEI or ARB, and a CCB. Mineralocorticoid (aldosterone) receptor antagonists like spironolactone are advantageous additions in this setting and have shown evidence of greater BP reduction than beta or alpha blockers. Vasodilators like hydralazine or minoxidil have also shown significant reductions in BP in these patients. Direct renin inhibitors like aliskiren show similar reductions in BP to ACEIs or ARBs but should not be used in combination with them due to increased likelihood of angioedema and hyperkalemia. Central alpha-2 agonists like clonidine are generally reserved as last line therapy due to adverse effects in the central nervous system, particularly in elderly populations.

2. Pregnancy

Women with hypertension who become pregnant or are planning to become pregnant, should be transitioned to methyldopa, nifedipine, and/or labetalol during pregnancy. Hydralazine is a reasonable addition to these medications if BP remains above goal, however, it should not be used as monotherapy. ACEIs, ARBs, and direct renin inhibitors are contraindicated in pregnancy.

Abigail Elmes
Kelly Karpa

General overview of the RAAS system: Cells and hormones

This 15-minute animated, narrated video describes the components and pathways involved with the renin-angiotensin-aldosterone system. The role of the RAAS and its regulation of blood pressure is also discussed. Suitable for beginners.

 Author: Rishi Desai, Khan Academy

Average: 4 (2 votes)

High Blood Pressure

This 7-minute animated, narrated video describes the factors affecting blood pressure such as cardiac output, blood volume, and vascular resistance. Methods of blood pressure measurement, long term consequences of elevated blood pressure, and treatments of hypertension are also briefly discussed. Suitable for beginners.

Author: Covenant Health

Average: 2.7 (3 votes)

Pharmacology – Hypertension & antihypertensives (made easy)

This 15-minute animated, narrated video describes the pharmacology of major classes of antihypertensive medications. The role of other medications such as bosentan, fenoldopam, hydralazine, and minoxidil is also discussed. Suitable for beginners.

Author: Speed Pharmacology

Average: 3.8 (5 votes)