Immunomodulatory Activity of the Most Commonly Used Antihypertensive Drugs—Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers

Abstract

This review article is focused on antihypertensive drugs, namely angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and their immunomodulatory properties reported in hypertensive patients as well as in experimental settings involving studies on animal models and cell lines. The immune regulatory action of ACEI and ARB is mainly connected with the inhibition of proinflammatory cytokine secretion, diminished expression of adhesion molecules, and normalization of CRP concentration in the blood plasma. The topic has significant importance in future medical practice in the therapy of patients with comorbidities with underlying chronic inflammatory responses. Thus, this additional effect of immune regulatory action of ACEI and ARB may also benefit the treatment of patients with metabolic syndrome, allergies, or autoimmune disorders.

Beta-blockers in patients with liver cirrhosis: Pragmatism or perfection?

“…There is strong evidence in the cardiovascular literature that activation and recruitment of inflammatory cells is mediated by the adrenergic system, especially via ß 2 -receptors ( 95 ), and that antihypertensive drugs ( 96 ) have a beneficial immunomodulatory effect.…”

Angiotensin Receptor Blockers in the Management of Hypertension: A Real-World Perspective and Current Recommendations

“…Atherosclerosis: decrease of PAI-1 in the vessel wall, reduced atherosclerosis progression and reduced instability of atherosclerotic plaque 39,40 MACE: reduced occurrence of stroke, MI, HF, CV mortality, death from any cause [41][42][43][44][45][46][47] Metabolic diseases: increased urinary uric acid excretion, activation of PPAR-γ, reduction of adipose tissue weight and of adipocyte size 14,31,32 Diabetes: reduction of the occurrence of new-onset diabetes, improvement of insulin sensitivity and HOMA-IR index 29,33 Chronic kidney disease: protective role toward the development of microalbuminuria, overt proteinuria, and the progression to end-stage renal disease [31][32][33][34][35][36] Side effects: reduced incidence of angioedema, cough, hypotension, syncope, and electrolyte abnormalities 52,[56][57][58] COVID-19: potential beneficial effects through vasodilatation, anti-inflammatory, anti-oxidative, and antiproliferative properties [60][61][62][63][64][65][66] Abbreviations: ACEi, angiotensin converting enzyme inhibitors; ARBs, angiotensin receptor blockers; CV, cardiovascular; HF, heart failure; HOMA-IR, homeostasis model assessment; LVH, left ventricular hypertrophy; MI, myocardial infarction; PAI-1, plasminogen activator inhibitor type-I; PPAR-γ, peroxisome proliferator-activated receptor.…”

“…Vascular Health and Risk Management 2022:18 510 Indeed, studies performed in patients with hypertension, stable angina or type 2 diabetes mellitus, the long-term treatment with ARBs showed a reduction in the levels of markers of vascular inflammation [high-sensitive C-reactive protein (CRP), alpha tumor necrosis factor, interleukin-6, and macrophage chemotactic protein-1], a regression of the atheromatous plaque volume at the carotid and coronary arteries and a regression of vascular hypertrophy. 41 In patients with high CV risk, ARBs have shown comparable protective effects with respect to ACEi. The ONTARGET (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial) study, which included 25,000 patients with coronary, peripheral or cerebrovascular disease and diabetes with end organ damage, demonstrated that telmisartan had similar effects compared to ramipril on the primary composite endpoint of CV death, MI, stroke or hospitalization for HF and death from any cause.…”

Monocyte and Macrophage Function Diversity

“…Macrophages are known to be major players in inflammatory diseases such as hypertension, which is associated with chronic inflammation. Bryniarski et al [ 7 ] analyzed how anti-hypertension drugs, angiotensin-converting enzyme (ACE2) inhibitors, and angiotensin II receptor blockers reduce the inflammatory activity of macrophages and other immune cells. In very informative tables they listed all studied drugs and their effect on molecules related to the immune response and different immune cells.…”

“…AT2R and ACE2 receptors initiate a signaling cascade in macrophages that modulate their activation and production of chemokines and cytokines. This is also very relevant to the recent COVID-19 pandemic because ACE2 receptors bind the SARS-CoV-2 Spike Protein, facilitating virus internalization and intercellular spreading [ 7 , 8 ]. The anti-hypertension drugs modulate immune response parameters not only in hypertensive but also in healthy patients; thus, their anti-inflammatory properties can be possibly used to treat other than hypertension inflammatory diseases including overreactive macrophages in viral infections.…”