Stimulation of histamine H₁-receptors produces a positive inotropic effect in the human atrium

There is a controversy whether histamine H₁-receptor activation raises or lowers or does not affect contractility in the human heart. Therefore, we studied stimulation of H₁-receptors in isolated electrically stimulated (one beat per second) human atrial preparations (HAP). For comparison, we measured force of contraction in left atrial preparations (LA) from mice with overexpression of the histamine H₁-receptor in the heart (H₁-TG). We detected the messenger ribonucleic acid (mRNA) expression of human histamine H₁-receptors in HAP. In LA from H₁-TG, each cumulatively applied concentration of histamine and a dual H₁/H₂-agonist called 2-(2-thiazolyl)-ethylamine (ThEA) caused a time-dependent initial negative inotropic effect followed over time by a lasting positive inotropic effect. Both effects were concentration-dependent in LA from H₁-TG. After 100 µM cimetidine, 10 µM histamine exercised a positive inotropic effect in HAP that was diminished by 10 µM mepyramine, an H₁-receptor antagonist. The concentrations of mepyramine and cimetidine used here are based on the work of others and our own work (e.g., Guo et al. J Cardiovasc Pharmacol. 6:1210-5 1984, Rayo Abella et al. J Pharmacol Exp Ther. 389:174-185 2024). Similarly, we observed that ThEA (10 µM, 30 µM, 100 µM cumulatively applied) induced a concentration- and time-dependent positive inotropic effect in HAP. In HAP, we detected never negative inotropic effects to either histamine or ThEA. The positive inotropic effects to ThEA in HAP were reduced by mepyramine. The positive inotropic effects of ThEA in LA from H₁-TG and in HAP were not accompanied by reductions in the time of tension relaxation. We conclude that stimulation of histamine H₁-receptors only increases and does not decrease force of contraction in the HAP in our patients.