Hypertension Pathophysiology and Pharmacotherapy

A complete glossary of vocabulary terms, concepts, and drug classes covering the pathophysiology, clinical categories, target-organ damage, and pharmacotherapy of hypertension.

Renin-Angiotensin-Aldosterone System (RAAS)

A neurohormonal system that regulates long-term blood pressure and extracellular fluid volume through a cascade involving renin, angiotensinogen, Angiotensin I, Angiotensin II, and aldosterone.

Angiotensinogen

A circulating protein produced and released by the liver in response to low blood pressure or changes in blood volume.

Renin

An enzyme secreted by the kidneys when blood volume or fluid pressure drops, responsible for converting angiotensinogen into Angiotensin I.

Angiotensin-Converting Enzyme (ACE)

An enzyme located in the lungs that converts Angiotensin I into Angiotensin II.

Angiotensin II

A potent vasoconstrictor formed in the RAAS pathway that stimulates aldosterone secretion, increases fluid retention, and contributes to inappropriate cardiac remodeling following a heart attack.

Aldosterone

A hormone secreted by the adrenal glands in response to Angiotensin II that acts on the nephrons to cause sodium and water retention while promoting potassium excretion.

Arterial Baroreceptors

Pressure-sensing receptors located in the carotid sinus, aorta, and left ventricle that alter blood pressure by modulating heart rate, vasodilation, and vasoconstriction.

Vascular Autoregulation

An intrinsic physiological mechanism that regulates arteriole diameter to maintain consistent tissue perfusion levels based on mean arterial pressure ($\text{MAP}$).

Primary Hypertension

High blood pressure with no known identifiable cause (idiopathic), resulting from complex interactions between genetics, the environment, SNS, RAAS, and natriuretic peptides; also called essential hypertension.

Secondary Hypertension

Hypertension resulting from an underlying identifiable disease or disorder, such as renal disease, adrenocortical tumors, pheochromocytoma, or specific drugs.

Blood Pressure Categories

Classifications defined by the American Heart Association: Normal ($<120$ and $<80\,\text{mmHg}$), Elevated ($120-129$ and $<80\,\text{mmHg}$), Stage 1 Hypertension ($130-139$ or $80-89\,\text{mmHg}$), Stage 2 Hypertension ($\ge 140$ or $\ge 90\,\text{mmHg}$), and Hypertensive Crisis ($>180$ and/or $>120\,\text{mmHg}$).

Target-Organ Damage

Vascular and tissue complications resulting from chronic hypertension, affecting the brain (TIA, stroke), heart (LVH, CHD, heart failure), kidneys (renal failure), eyes (retinopathy), and blood vessels (PVD).

Hypertensive Emergency

Severe blood pressure elevation ($>180/120\,\text{mmHg}$) with active signs or symptoms of end-organ damage (e.g., headache, blurry vision, stroke, chest pain), requiring immediate aggressive IV medication to lower blood pressure within minutes to hours.

Hypertensive Urgency

Severely elevated blood pressure ($>180/120\,\text{mmHg}$) without evidence of end-organ damage, treated with oral agents to gradually reduce blood pressure over time.

Diuretics

Antihypertensive medications that promote urinary output, decrease circulating blood volume, lower cardiac output, and reduce arterial resistance by blocking sodium and chloride reabsorption.

Thiazide Diuretics

First-line diuretics for mild hypertension (e.g., hydrochlorothiazide [HCTZ], metolazone) that inhibit sodium, potassium, and chloride reabsorption in the distal convoluted tubule and relax arterioles.

Loop Diuretics

Potent diuretics (e.g., furosemide, bumetanide, torsemide) that block sodium reabsorption in the Loop of Henle, producing profound diuresis to reduce fluid volume in blood vessels.

Hypokalemia

A condition characterized by abnormally low blood potassium levels ($<3.5\,\text{mmol/L}$), categorized as mild ($3.0-3.4\,\text{mmol/L}$), moderate ($2.5-2.9\,\text{mmol/L}$), or severe ($<2.5\,\text{mmol/L}$); a common side effect of loop and thiazide diuretics.

Potassium-Sparing Diuretics

Aldosterone antagonists (e.g., spironolactone) that block aldosterone action, promoting sodium and water excretion while retaining potassium.

ACE Inhibitors

First-line antihypertensive agents ending in '-pril' (e.g., captopril, lisinopril, enlapril, benazepril, ramipril) that block angiotensin-converting enzyme to inhibit Angiotensin II production and reduce aldosterone secretion.

Angioedema

A rare but serious adverse effect of ACE inhibitors involving deep tissue swelling of the lips, eyes, tongue, face, or airway, which occurs at a higher frequency in African American patients ($5.5\%$) compared to others ($0.1-0.7\%$).

Angiotensin Receptor Blockers (ARBs)

Antihypertensive drugs ending in '-sartan' (e.g., losartan, eprosartan, valsartan, olmesartan) that block the action of Angiotensin II at receptor sites after it has been formed.

Calcium Channel Blockers (CCBs)

Antihypertensive agents (e.g., nifedipine, amlodipine, nicardipine, verapamil, diltiazem) that block calcium entry into vascular and cardiac cells, decreasing contractility, conductivity, oxygen demand, and blood pressure.

CCB-Induced Pedal Edema

Lower extremity swelling caused when dihydropyridine CCBs (such as amlodipine) selectively dilate arterioles without dilating venules, leading to elevated capillary hydrostatic pressure and fluid expulsion into surrounding tissue.

Sympatholytics

Classes of drugs (including alpha-blockers, beta-blockers, and central alpha-2 agonists) that block sympathetic nervous system activity to decrease peripheral vascular resistance and blood pressure.

Cardioselective Beta Blockers

Antihypertensive drugs ending in '-olol' (e.g., metoprolol, atenolol, bisoprolol) that selectively block $\beta_1$ receptors in the heart to decrease heart rate, contractility, and renin secretion.

Rebound Hypertension

A critical, sudden rise in blood pressure that occurs when antihypertensive medications (such as beta-blockers or clonidine) are abruptly discontinued.

Centrally Acting Alpha-2 Agonists

Sympatholytic agents (e.g., clonidine) that stimulate central alpha-2 receptors to decrease sympathetic outflow, thereby reducing both alpha and beta receptor stimulation and lowering blood pressure.

Selective Alpha-1 Blockers

Antihypertensive agents (e.g., doxazosin) that block selective alpha-1 adrenergic receptors, inducing venous and arterial dilation to lower blood pressure.

Direct Vasodilators

Antihypertensive agents (e.g., hydralazine) that act directly on vascular smooth muscle to cause arterial relaxation and reduce systemic peripheral vascular resistance.