Molecular mechanisms and clinical pharmacodynamics of antihypertensive agents: a contemporary integrative review

Abstract

Background: Arterial hypertension remains a leading global risk factor for cardiovascular morbidity and mortality. Effective pharmacotherapy hinges on a precise understanding of the molecular mechanisms, receptor dynamics, and tissue-specific effects of antihypertensive agents. Objective: This review aims to integrate current knowledge of the clinical pharmacology of major antihypertensive drug classes, focusing on their receptor targets, pharmacodynamic profiles, and clinical implications, to guide personalized therapy. Methods: We performed a narrative integrative review, synthesizing primary pharmacology literature, clinical trials, and mechanistic studies. Major databases (PubMed, NCBI Bookshelf) and recent pharmacology reviews were searched for peer-reviewed articles on diuretics, ACE inhibitors, angiotensin receptor blockers (ARBs), beta-blockers, and calcium-channel blockers. Results: Each drug class acts via distinct yet overlapping molecular pathways. Diuretics reduce intravascular volume via renal sodium transporters; ACE inhibitors decrease angiotensin II production and increase bradykinin; ARBs block AT₁ receptors; beta-blockers inhibit β-adrenergic signaling reducing heart rate, renin release, and contractility; calcium-channel blockers inhibit L-type (and in some drugs T-type) calcium channels, leading to vascular smooth muscle relaxation (dihydropyridines) or negative inotropy/conduction (non-dihydropyridines). Clinical pharmacodynamics show class- and agent-specific onset, tissue selectivity, and side-effect profiles. Conclusions: Understanding the nuanced molecular pharmacology of antihypertensives facilitates rational drug selection tailored to individual patient profiles (e.g., comorbidities, tolerability). Future research should further explore emerging targets and precision medicine approaches to optimize antihypertensive therapy.