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Neurohormonal modulation in cardiovascular disease.

¹Institute of Pharmacology, Christian Albrechts University.

American Heart Journal

|January 5, 2000

Summary

The renin-angiotensin system (RAS) involves angiotensin II (Ang II) acting on AT(1) and AT(2) receptors. AT(1) antagonists, or sartans, are effective hypertension treatments, but understanding AT(2) receptor function is crucial for their full therapeutic potential.

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Area of Science:

Cardiovascular Physiology
Endocrinology
Pharmacology

Background:

The renin-angiotensin system (RAS) is a critical hormonal system regulating blood pressure and fluid balance.
Angiotensin II (Ang II) exerts its effects through two main receptor subtypes: AT(1) and AT(2).
AT(1) receptors mediate vasoconstriction, salt/water retention, and aldosterone release, while also contributing to hypertrophy and atherosclerosis.

Purpose of the Study:

To elucidate the distinct roles of AT(1) and AT(2) receptors in mediating the effects of Ang II.
To compare the mechanisms of action and therapeutic potential of AT(1) receptor antagonists (sartans) versus angiotensin-converting enzyme (ACE) inhibitors.
To highlight the importance of understanding AT(2) receptor function in the context of AT(1) antagonist therapy for target-organ protection.

Main Methods:

Review of existing physiological and pharmacological data on the RAS, Ang II, and its receptors.
Analysis of the mechanisms by which AT(1) receptor antagonists (sartans) inhibit the RAS.
Comparison of the effects of sartans and ACE inhibitors on cardiovascular and renal systems.

Main Results:

AT(1) receptors are primarily responsible for the deleterious effects of Ang II, including vasoconstriction and organ damage.
AT(2) receptors are associated with antiproliferative effects, tissue regeneration, and antagonism of AT(1) actions.
AT(1) receptor antagonists (sartans) offer a more complete blockade of the RAS compared to ACE inhibitors and show potential for target-organ protection.

Conclusions:

The balance between AT(1) and AT(2) receptor signaling determines the net physiological outcome of Ang II.
Sartans represent a significant therapeutic advance in hypertension management, offering an alternative to ACE inhibitors.
Further research into AT(2) receptor function is essential for optimizing the use of AT(1) antagonists and maximizing their benefits, particularly in preventing target-organ damage.

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