A Review on Advancements in Hypertension Research: Experimental Models, Mechanisms, and Therapeutic Targets

Abstract

Background: Hypertension is one of the most prevalent cardiovascular disorders and a major global cause of morbidity and mortality, affecting approximately one billion individuals worldwide. Despite advances in screening and diagnosis, adequate blood pressure control remains suboptimal, particularly in countries such as India, where its prevalence among adults continues to increase. Limitations associated with conventional renin–angiotensin–aldosterone system (RAAS) inhibitors have prompted interest in novel therapeutic strategies for more effective blood pressure control and cardiovascular risk reduction.

Methods: This review examines the historical evolution of hypertension research and antihypertensive therapeutics, with particular emphasis on the limitations of conventional RAAS-targeting therapies and emerging pharmacological approaches. Contemporary evidence from clinical trials and relevant research on the ACE2/Ang-(1–7)/Mas receptor axis, neprilysin inhibition, technological advances, and innovative treatment strategies was critically evaluated. The review also considers relevant legislative and public health policy initiatives influencing hypertension management.

Results: The evidence indicates that modulation of alternative components of the RAAS may provide additional therapeutic benefits beyond conventional RAAS inhibition. Targeting the ACE2/Ang-(1–7)/Mas receptor axis may promote vasodilatory and cardioprotective effects, while neprilysin inhibition represents another promising approach for improving blood pressure regulation and cardiovascular outcomes. However, challenges related to therapeutic efficacy, patient heterogeneity, long-term cardiovascular benefits, and implementation remain. Advances in technology and emerging pharmacological strategies may further improve hypertension detection, monitoring, and treatment.

Conclusions: Hypertension management is evolving beyond conventional RAAS inhibition toward more targeted and innovative therapeutic approaches. Modulation of the ACE2/Ang-(1–7)/Mas receptor pathway and neprilysin inhibition represents promising areas for future drug development. Continued integration of clinical evidence, technological innovation, and effective health policies may contribute to more individualized and effective hypertension management and potentially transform cardiovascular outcomes in the future.