The Roles of Cardiovascular H2-Histamine Receptors Under Normal and Pathophysiological Conditions

Abstract

This review addresses pharmacological, structural and functional relationships among H2-histamine receptors and H1-histamine receptors in the mammalian heart. The role of both receptors in the regulation of force and rhythm, including their electrophysiological effects on the mammalian heart, will then be discussed in context. The potential clinical role of cardiac H2-histamine-receptors in cardiac diseases will be examined. The use of H2-histamine receptor agonists to acutely increase the force of contraction will be discussed. Special attention will be paid to the potential role of cardiac H2-histamine receptors in the genesis of cardiac arrhythmias. Moreover, novel findings on the putative role of H2-histamine receptor antagonists in treating chronic heart failure in animal models and patients will be reviewed. Some limitations in our biochemical understanding of the cardiac role of H2-histamine receptors will be discussed. Recommendations for further basic and translational research on cardiac H2-histamine receptors will be offered. We will speculate whether new knowledge might lead to novel roles of H2-histamine receptors in cardiac disease and whether cardiomyocyte specific H2-histamine receptor agonists and antagonists should be developed.

Possible Association between the Use of Proton Pump Inhibitors and H2 Receptor Antagonists, and Esophageal Cancer: A Nested Case–Control Study Using a Korean National Health Screening Cohort

“…Theoretically, H 2 receptors are mainly distributed in the myocardium of the right atrium and ventricle in animal studies [ 36 ]. Functional or structural alterations of H 2 receptors in cardiomyocytes may lead to cardiac arrhythmias [ 37 ]. Thus, the negative impact of H2RA might more likely happen in elderly patients, which might eventually indirectly increase the patients’ death ratio.…”

Impact of Acid Suppression Therapy on Renal and Survival Outcomes in Patients with Chronic Kidney Disease: A Taiwanese Nationwide Cohort Study

“…Histamine-2-receptor (H2R) antagonist (H2RA) and proton pump inhibitor (PPI) are the main options for acid suppression therapy available at present, with PPI being more expensive, high-profile, and over-prescribed worldwide [ 1 ] than H2RA. Experimental data has shown a pathophysiological role of histamine signaling and H2R activation in response to histamine in the kidney, heart, and immune response [ 2 , 3 , 4 , 5 ]. H2Rs are found in mammalian and human cardiomyocytes, throughout the kidney and renal vessels, in the stomach and in neutrophils [ 2 , 3 , 4 , 5 ].…”

“…Experimental data has shown a pathophysiological role of histamine signaling and H2R activation in response to histamine in the kidney, heart, and immune response [ 2 , 3 , 4 , 5 ]. H2Rs are found in mammalian and human cardiomyocytes, throughout the kidney and renal vessels, in the stomach and in neutrophils [ 2 , 3 , 4 , 5 ]. Histamine (via the H2R) mediates inflammation, which is central to renal diseases, reduces renal blood flow and creatinine and urea clearance at high doses, and modifies activated neutrophils, triggering oxidative burst and the release of reactive oxygen species; H2R activation stimulates renin release, promotes cardiac fibrosis and apoptosis, and plays a role in immune response [ 2 , 3 , 4 , 5 ].…”

“…H2Rs are found in mammalian and human cardiomyocytes, throughout the kidney and renal vessels, in the stomach and in neutrophils [ 2 , 3 , 4 , 5 ]. Histamine (via the H2R) mediates inflammation, which is central to renal diseases, reduces renal blood flow and creatinine and urea clearance at high doses, and modifies activated neutrophils, triggering oxidative burst and the release of reactive oxygen species; H2R activation stimulates renin release, promotes cardiac fibrosis and apoptosis, and plays a role in immune response [ 2 , 3 , 4 , 5 ]. Therefore, it seems biologically plausible that H2RA haspotential beneficial effects on the kidney, heart, and survival.…”

“…Animal interventional models of ischemic acute renal failure, pressure-induced heart failure, and sepsis and clinical studies of patients with heart failure and COVID-19 infection have provided evidence that H2RA could improve heart and renal functions, such as reduced levels of serum creatinine and blood urea nitrogen, and lower mortality [ 3 , 4 , 5 , 13 , 14 , 15 , 16 , 17 , 18 ]. However, there is a lack of clinical human evidence to address the impact of H2RA on the renal outcome.…”