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Received for publication November 20, 2003.
Revised January 14, 2004.
Accepted for publication January 29, 2004.
Histamine is highly concentrated in the heart of animals and humans. Excessive release in pathophysiological conditions, such as immediate hypersensitivity and septic shock, causes cardiac dysfunction and arrhythmias. Previous pharmacological studies revealed that H1- and H2-receptors mediate these effects. Yet, an accurate estimate of the distribution and molecular characteristics of cardiac histamine receptors is missing. Recently, the genes encoding H1- and H2-receptors have been cloned, and the amino acid sequence and protein structure have been elucidated. Accordingly, we analyzed gene and protein expression levels of H1- and H2-receptors in atria and ventricles of guinea pig, rabbit, rat and human hearts. With immunocytochemical techniques we examined the regional expression of H1- and H2-receptor proteins in the sinoatrial and atrioventricular nodes and surrounding myocardium of the guinea-pig heart. Northern and Western blot studies revealed that cardiac histamine H1- and H2-receptors are variably distributed among different mammalian species and different regions of the heart, while H2-receptors are abundantly expressed in human atrial and ventricular myocardium. These findings agree with those of previous pharmacological studies, clearly demonstrating that the responses of the heart to histamine depend on the expression level of H1- and H2-receptors. The highly abundant expression of H2-receptors in the human heart substantiates histamine arrhythmogenicity in various disease states. The new knowledge of a differential distribution of histamine receptor subtypes in the human heart will foster a better understanding of histamine roles in cardiovascular pathophysiology and may contribute to new therapeutic approaches to histamine-induced cardiac dysfunctions.
Key words:
Heart, Histamine H<SUB>1</SUB>-receptor, Histamine H<SUB>2</SUB>-receptor, Immunohistochemistry, Northern blot, Western blot
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