Learning Objectives

By the end of this lesson, the learner should be able to:

• Describe the role of the renin–angiotensin–aldosterone system (RAAS) in blood pressure regulation.
• Compare the mechanisms of action of ACE inhibitors, ARBs, and renin inhibitors.
• Identify the major clinical uses of RAAS-blocking drugs.
• Recognize the key adverse effects and contraindications associated with these agents.
• Relate the site of vascular action of antihypertensive drugs to their physiological consequences.

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The Angiotensin System (Overview)

The renin–angiotensin–aldosterone system plays a central role in regulating blood pressure through effects on vascular tone, sodium balance, and intravascular volume. Interruption of this pathway lowers blood pressure primarily by reducing angiotensin II–mediated vasoconstriction and aldosterone secretion.

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Drugs and Mechanisms

ACE Inhibitors (ACEIs)

Examples: captopril, lisinopril (and other “-prils”)

• Inhibit conversion of angiotensin I to angiotensin II
• Prevent stimulation of AT₁ receptors
• Decrease aldosterone secretion
• Produce vasodilation
• Inhibits the degradation of bradykinin, contributing to vasodilation and certain adverse effects

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Angiotensin II Receptor Blockers (ARBs)

Examples: losartan (and other “-sartans”)

• Directly block AT₁ receptors
• Produce blood pressure effects similar to ACE inhibitors
• Do not interfere with bradykinin degradation

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Renin Inhibitor

Example: aliskiren

• Inhibits renin, blocking the formation of angiotensin I
• Produces blood pressure effects similar to ACE inhibitors
• Does not affect bradykinin metabolism

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Clinical Uses

• Mild-to-moderate hypertension (all agents)
• Renal protection in diabetic nephropathy (ACEIs and ARBs)
• Chronic heart failure (ACEIs and ARBs)

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Adverse Effects

• Dry cough (ACE inhibitors only)
• Hyperkalemia
• Acute renal failure in patients with renal artery stenosis
• Angioedema

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Contraindication

Pregnancy (all RAAS-blocking agents)

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Bridge to Physiology

Vascular Specificity of Vasodilators

Antihypertensive drugs differ in their primary site of action within the vasculature:

• Arteriolar dilation:
  Calcium channel blockers, hydralazine, potassium channel openers
• Venular dilation:
  Nitrates
• Both arteriolar and venular dilation:
  Most other vasodilators

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Orthostatic Hypotension

Orthostatic (postural) hypotension results primarily from venular dilation, not arteriolar dilation. It is most commonly associated with:

• α₁-adrenergic blockade
• Decreased sympathetic tone

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Activity