Renin inhibition--benefit beyond hypertension control

Area of Science:

• Cardiovascular Pharmacology
• Renal Physiology
• Endocrinology

Background:

• The renin-angiotensin system (RAS) is crucial for blood pressure and electrolyte balance.
• Overactivation of the angiotensin AT1-receptor by angiotensin II (AII) increases blood pressure and causes end-organ damage.
• Current treatments like ACE inhibitors and ARBs incompletely block the RAS due to AII formation via indirect pathways and compensatory renin release.

Purpose of the Study:

• To highlight renin inhibition as a preferred pharmacologic strategy for RAS blockade.
• To discuss the long-standing recognition of renin inhibition's advantages.
• To note recent advancements in developing clinically effective renin inhibitors.

Main Methods:

• Review of established knowledge on RAS function and regulation.
• Analysis of the limitations of current antihypertensive therapies (ACE inhibitors, ARBs).
• Discussion of the rationale for targeting renin as the rate-limiting step in RAS activation.

Main Results:

• Renin inhibition provides a more complete blockade of the RAS compared to ACE inhibitors and ARBs.
• Inhibiting renin addresses the issue of compensatory renin release seen with other drug classes.
• Recent development has led to clinically effective renin inhibitors, exemplified by Aliskiren.

Conclusions:

• Renin inhibition represents a highly effective approach to pharmacologically block the RAS.
• Aliskiren's approval signifies a major advancement in RAS-targeted therapies.
• Targeting renin offers a promising strategy for managing hypertension and cardiovascular diseases.