Yulia V. Stepenko, Olesya V. Shcheblykina, Anna A. Peresypkina, Veronika S. Shmigerova, Yomna Y.O.M. Akhmed , Tatiana A. Denisyuk, Anton P. Danilenko, Nikita S. Lyapkalov, Elena A. Shmykova, Lyudmila M. Danilenko

Nonclassical cardiovascular effects of imidazoline receptor agonists

Introduction

Nonclassical cardiovascular effects of imidazoline receptor agonists. Imidazoline receptor agonists show nonclassical cardiovascular effects, lowering blood pressure, improving metabolism & inflammation. Effective for heart failure, hypertension & LVH.

Abstract

Introduction: Imidazoline receptors are a group of metabotropic receptors whose activation is associated with changes in a number of functional parameters, including hemodynamics (lowering blood pressure (BP), negative chrono-and inotropic effects), metabolic metabolism (reducing insulin resistance, increasing high-density lipoproteins (HDL) levels) and hemorheology (antiplatelet activity). In addition, the spectrum of molecular pharmacological effects of imidazoline receptor (IR) agonists includes anti-inflammatory, antioxidant, and antifibrinolytic activities. Materials and Methods: Literature sources were searched using PubMed and Google Scholar databases, including such article types as meta-analysis, randomized controlled trial, and review. The inclusion criteria were full availability of data, scientific significance, and relevance of research. Results and Discussion: Experimental studies in animals revealed such effects of agonists IR as a decrease in the degree of left ventricular hypertrophy (LVH) and interleukin expression. The experience of using agonists IR therapy in clinical practice has revealed its effectiveness in the treatment of patients with chronic heart failure (CHF) II-IIIof NYHA class II-III NYHA with an ejection fraction of less than 40%, arterial hypertension (AH) and microalbuminuria. Conclusions: In general, the totality of data available to date indicates a high expediency of including imidazoline receptors in the repertoire of pharmacological targets, the impact on which can affect not only soft, but also hard endpoints in the treatment of cardiovascular pathology.

Review

The manuscript provides a timely and important review of the "nonclassical" cardiovascular effects of imidazoline receptor (IR) agonists. The authors set out to synthesize current knowledge regarding the diverse physiological and molecular impacts of IR activation beyond conventional hemodynamic changes. The introduction effectively establishes the broad spectrum of effects, encompassing not only blood pressure regulation but also metabolic modulation (e.g., insulin resistance, HDL levels), hemorheological benefits (antiplatelet activity), and critical molecular activities such as anti-inflammatory, antioxidant, and antifibrinolytic properties. This comprehensive scope underscores the potential for IR agonists to represent a significant class of therapeutic agents in cardiovascular medicine. A key strength highlighted in the abstract is the clear demonstration of IR agonists' multifaceted actions from both experimental and clinical perspectives. The review synthesizes evidence from animal studies, revealing promising effects such as the reduction of left ventricular hypertrophy and the attenuation of interleukin expression, indicative of anti-remodeling and anti-inflammatory roles. Furthermore, the clinical experience presented showcases their efficacy in challenging patient populations, including those with chronic heart failure (NYHA II-III with reduced ejection fraction), arterial hypertension, and microalbuminuria. These findings collectively build a compelling case for IR agonists as agents capable of influencing both intermediate (soft) and long-term (hard) cardiovascular endpoints. While the abstract convincingly argues for the high expediency of considering imidazoline receptors as valuable pharmacological targets, a deeper understanding of the specific mechanisms underlying each nonclassical effect, especially in a comparative context, would further enrich the overall narrative. Given this is a review, the strength lies in synthesizing existing data; however, the abstract's conclusions hint at the need for continued rigorous research, particularly concerning long-term outcome studies that firmly establish the impact on "hard endpoints." Nevertheless, the presented overview strongly supports the notion that IR agonists offer a promising therapeutic avenue that warrants further comprehensive investigation and clinical application in cardiovascular pathology.

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