Angiotensin receptor blockers (ARBs) mechanism of action
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Angiotensin Receptor Blockers (ARBs) Mechanism of Action
AT1 Receptor Blockade and Blood Pressure Reduction
Angiotensin receptor blockers (ARBs) work by selectively blocking the angiotensin II type 1 (AT1) receptor. This prevents angiotensin II—a hormone that normally causes blood vessels to constrict and raises blood pressure—from binding to its main receptor, leading to relaxation of blood vessels, increased salt and water excretion, reduced plasma volume, and decreased cellular hypertrophy. The result is a lowering of blood pressure, mainly through reduced peripheral vascular resistance, usually without an increase in heart rate 1256.
Surmountable vs. Insurmountable Antagonism
ARBs can be classified based on how they bind to the AT1 receptor. Some are surmountable antagonists, meaning their effects can be overcome by high levels of angiotensin II, while others are insurmountable, providing more sustained receptor blockade. These differences in binding kinetics may influence the clinical effects and duration of action of different ARBs 1.
Effects on AT2 Receptors and Additional Benefits
By blocking AT1 receptors, ARBs allow angiotensin II to act more on unblocked type 2 (AT2) receptors. Stimulation of AT2 receptors may have beneficial effects, such as neuroprotection and vascular repair, especially in conditions like stroke. This dual action—blocking harmful AT1 effects while allowing potentially beneficial AT2 effects—may contribute to the protective benefits of ARBs beyond just lowering blood pressure 36.
Non-ACE Pathways and Complete Inhibition
Unlike ACE inhibitors, which only block the conversion of angiotensin I to angiotensin II, ARBs block the action of angiotensin II regardless of how it is produced, including through non-ACE pathways like chymase. This means ARBs may offer more complete inhibition of angiotensin II’s effects 12.
Pleiotropic and Neuroprotective Effects
ARBs have additional effects beyond blood pressure control. They can reduce inflammation, protect the heart and kidneys, and may even have neuroprotective actions by entering the brain and reducing injury in conditions like stroke, Alzheimer’s, and Parkinson’s disease. Some ARBs also inhibit enzymes in the brain that are linked to cognitive impairment, suggesting possible benefits in treating or preventing brain disorders 36789.
Clinical Implications
ARBs are effective for treating hypertension and are also used in heart failure and diabetic nephropathy, especially in patients who cannot tolerate ACE inhibitors. They have a low incidence of side effects and may provide organ protection in various conditions. Their unique mechanism—blocking AT1 receptors and allowing AT2 receptor stimulation—underlies many of their beneficial effects 256.
Conclusion
ARBs lower blood pressure by selectively blocking the AT1 receptor, preventing the harmful effects of angiotensin II. Their mechanism allows for additional benefits, including organ protection and possible neuroprotection, making them a valuable option in the management of hypertension and related conditions 12356789.
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