What is the mechanism of action of aliskiren (Tekturna)?

October 9, 2025 •

4 min read

As the first in a class of medications known as direct renin inhibitors, aliskiren (Tekturna) offers a unique way to manage high blood pressure. It targets the very first step of the body's renin-angiotensin-aldosterone system (RAAS), a hormonal pathway that regulates blood pressure. Unlike more common blood pressure medications that act further down this cascade, aliskiren provides a distinct point of therapeutic intervention for controlling hypertension.

Quick Summary

Aliskiren (Tekturna) is a direct renin inhibitor that lowers blood pressure by blocking the enzyme renin, the initial step of the RAAS pathway. This prevents the formation of angiotensin I and subsequently, the powerful vasoconstrictor angiotensin II, leading to relaxed blood vessels and reduced blood pressure.

Key Points

Direct Renin Inhibition: Aliskiren acts by directly inhibiting the enzyme renin, the first and rate-limiting step in the RAAS pathway.
Reduces Blood Pressure: By blocking renin, aliskiren prevents the formation of angiotensin I and II, resulting in the relaxation of blood vessels and a reduction in blood pressure.
Suppresses Plasma Renin Activity (PRA): Unlike ACE inhibitors and ARBs, aliskiren causes a net reduction in PRA by directly blocking the enzyme, even with compensatory increases in renin production.
Not for Combination Therapy in Diabetics: Combining aliskiren with ACE inhibitors or ARBs is contraindicated in patients with diabetes due to increased risks of kidney problems, high potassium, and low blood pressure.
Potential for Serious Side Effects: While often well-tolerated, aliskiren can cause serious side effects like angioedema (swelling) and hyperkalemia (high potassium levels).

Understanding the Renin-Angiotensin-Aldosterone System (RAAS)

To fully grasp how aliskiren works, one must first understand the RAAS, a complex hormonal pathway that plays a critical role in regulating blood pressure and fluid balance in the body. The cascade begins in the kidneys, which produce and release an enzyme called renin in response to low blood volume or low blood pressure. Renin then acts on a protein in the blood called angiotensinogen, cleaving it to form angiotensin I.

Angiotensin I is then converted into angiotensin II by another enzyme called angiotensin-converting enzyme (ACE). Angiotensin II is a potent molecule with several effects on the body:

Vasoconstriction: It causes the narrowing of blood vessels, which increases blood pressure.
Aldosterone release: It stimulates the adrenal glands to release aldosterone, a hormone that promotes sodium and water retention by the kidneys, further increasing blood pressure.
Sympathetic activity: It increases sympathetic nervous system activity, which contributes to higher heart rate and blood pressure.

In healthy individuals, this system is tightly regulated. However, in people with hypertension, the RAAS can be overactive, leading to chronically high blood pressure. Many antihypertensive drugs work by interrupting this cascade at different points.

The Unique Mechanism of Aliskiren

As a direct renin inhibitor, aliskiren (Tekturna) stands apart from other common blood pressure medications because it targets the RAAS at its origin.

How aliskiren interrupts the RAAS

Direct Renin Inhibition: Aliskiren binds directly and tightly to the active site of the renin enzyme.
Initial Cascade Blockade: By inhibiting renin, aliskiren prevents the crucial first step of the RAAS—the conversion of angiotensinogen to angiotensin I.
Cascade Interruption: This inhibition effectively blocks the entire downstream cascade, leading to reduced levels of both angiotensin I and the powerful vasoconstrictor angiotensin II.
Lowered Blood Pressure: The result is a relaxation of blood vessels and a decrease in sodium and water retention, which lowers overall blood pressure.

Effects on Plasma Renin Activity (PRA)

One of the most notable features of aliskiren is its effect on plasma renin activity (PRA). When ACE inhibitors or angiotensin receptor blockers (ARBs) are used, the body's natural feedback loop causes an increase in renin production and PRA. However, since aliskiren directly blocks renin, it causes a marked reduction in PRA, effectively suppressing the system's activity.

Comparison of RAAS-Blocking Medications

Aliskiren is not the only medication that works on the RAAS. Here is a comparison of aliskiren with other common classes of antihypertensive drugs.


Feature	Aliskiren (Direct Renin Inhibitor)	ACE Inhibitors (e.g., Lisinopril)	Angiotensin Receptor Blockers (ARBs) (e.g., Valsartan)
Mechanism	Directly inhibits renin, blocking the conversion of angiotensinogen to angiotensin I.	Inhibits the ACE enzyme, preventing the conversion of angiotensin I to angiotensin II.	Blocks the angiotensin II receptor, preventing angiotensin II from binding.
Point of Action	First step of the RAAS cascade.	Mid-step of the RAAS cascade.	End-step of the RAAS cascade.
Effect on PRA	Markedly reduces plasma renin activity.	Increases plasma renin activity due to loss of negative feedback.	Increases plasma renin activity due to loss of negative feedback.
Common Side Effects	Diarrhea, rash, cough (less common than ACEIs).	Persistent dry cough is a common side effect.	Fewer side effects than ACEIs, especially cough.
Angioedema Risk	Can cause angioedema, a serious allergic reaction, though incidence is low.	Known risk of angioedema.	Lower risk of angioedema than ACEIs.

Clinical Considerations and Safety

While aliskiren offers a novel approach, it is not without important clinical considerations.

Combination with Other RAAS Blockers: Studies have shown that combining aliskiren with an ACE inhibitor or ARB, especially in patients with diabetes, increases the risk of renal impairment, hyperkalemia (high potassium), and hypotension. Therefore, this combination is contraindicated in diabetic patients.
High-Fat Meals: The absorption of aliskiren can be significantly decreased by high-fat meals. It is recommended to take the medication consistently with or without food.
Pregnancy: Like other RAAS inhibitors, aliskiren is unsafe for use during pregnancy as it can cause harm or death to the fetus during the second and third trimesters.

Conclusion

Aliskiren (Tekturna) represents a unique and effective strategy for managing hypertension by acting as a direct renin inhibitor. By targeting the very start of the RAAS cascade, it prevents the formation of key vasoconstrictors and effectively lowers blood pressure. Although it provides an alternative for patients who may not tolerate the cough associated with ACE inhibitors, its use requires careful consideration, particularly regarding drug interactions and contraindications in specific patient populations. As with any medication, its use should be guided by a healthcare professional to ensure both efficacy and safety.

Frequently Asked Questions

Aliskiren inhibits the RAAS pathway at its starting point by directly blocking the renin enzyme, while ACE inhibitors block the ACE enzyme, a later step in the cascade.

Aliskiren can be used in combination with some other antihypertensives, but should not be combined with ACE inhibitors or ARBs, especially in patients with diabetes, due to safety concerns.

Common side effects include diarrhea, cough, headache, dizziness, and fatigue. The cough is less frequent than with ACE inhibitors.

You should avoid potassium supplements and salt substitutes containing potassium. High-fat meals can also decrease the absorption of aliskiren, so consistent timing with or without food is important.

Aliskiren can cause severe injury or death to an unborn baby, particularly during the second and third trimesters of pregnancy.

While a cough is a possible side effect, it is significantly less common with aliskiren compared to ACE inhibitors.

Aliskiren can cause high potassium levels (hyperkalemia), especially when combined with other RAAS inhibitors or in patients with kidney problems. Regular blood monitoring is necessary.