Renin Angiotensin Blockers and Cardiac Protection: From Basis to Clinical Trials

Area of Science:

• Pharmacology
• Cardiovascular Medicine
• Nephrology

Background:

• Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) similarly lower blood pressure.
• Clinical trials indicate ARBs may increase cardiovascular mortality and reduce myocardial infarction protection compared to ACEIs.
• European guidelines recommend ARBs for patients intolerant to ACEIs.

Purpose of the Study:

• To review pharmacological differences between ACEIs and ARBs.
• To elucidate how these differences impact cardiac protection.
• To provide insights into the distinct cardiovascular effects of ACEIs and ARBs.

Main Methods:

• Review of existing clinical trials and meta-analyses comparing ACEIs and ARBs.
• Analysis of pharmacological mechanisms of action for both drug classes.
• Examination of effects on bradykinin, nitric oxide, and angiotensin II receptor signaling.

Main Results:

• ACEIs uniquely affect bradykinin levels and nitric oxide bioavailability, influencing endothelial function, atherogenesis, and fibrinolysis.
• ARBs cause a sustained increase in plasma angiotensin II, potentially overstimulating available receptors.
• Animal models suggest AT4 and AT2 receptor activation by angiotensin II may have deleterious effects in certain conditions.

Conclusions:

• Pharmacological distinctions, particularly ACEIs' effects on bradykinin and nitric oxide, may explain differing cardiovascular outcomes.
• The chronic increase in angiotensin II and potential AT2 receptor overstimulation with ARBs warrant consideration.
• Reserve ARBs for patients with ACEI intolerance due to potential adverse cardiovascular effects.