From the Research
Angiotensin receptor-neprilysin inhibitors (ARNi) dilate afferent arterioles in the kidney, improving renal blood flow and glomerular filtration rate, as demonstrated in the most recent study 1.
Mechanism of Action
ARNi medications like sacubitril/valsartan work through dual mechanisms: blocking the angiotensin II type 1 receptor while simultaneously inhibiting neprilysin, an enzyme that breaks down natriuretic peptides. This combination leads to vasodilation of the afferent arteriole while maintaining efferent arteriole tone, which helps reduce intraglomerular pressure.
Clinical Implications
The vasodilatory effect occurs because natriuretic peptides (which increase when neprilysin is inhibited) promote relaxation of vascular smooth muscle, while the angiotensin receptor blockade prevents the vasoconstriction normally caused by angiotensin II. This hemodynamic effect contributes to the renoprotective benefits of ARNi therapy, making these medications valuable for patients with heart failure, particularly those with reduced ejection fraction, as they improve renal perfusion while reducing cardiac workload, as shown in a study published in the Journal of cardiovascular pharmacology and therapeutics 1.
Treatment Approach
Patients typically start with lower doses (such as sacubitril/valsartan 24/26 mg twice daily) and titrate upward as tolerated while monitoring blood pressure, renal function, and potassium levels.
Key Considerations
It is essential to consider the patient's kidney function and adjust the dose accordingly, as neprilysin inhibitors can accumulate in patients with impaired renal function, leading to potential side effects like hypotension, as noted in a study published in Current hypertension reports 2.
Recent Findings
A recent study published in the Journal of cardiac failure found that ARNi use was associated with significant reduction in blood pressure compared to ACEI/ARB group overall and across the eGFR spectrum, including in advanced chronic kidney disease 3.
Future Perspectives
The role of ARNi in various cardiovascular disorders, including heart failure with reduced ejection fraction, hypertension, and chronic kidney disease, continues to evolve, with ongoing research aiming to further elucidate its benefits and potential applications, as discussed in a review published in Future cardiology 4.