The Histamine 3 Receptor Is Expressed in the Heart and Its Activation Opposes Adverse Cardiac Remodeling in the Angiotensin II Mouse Model.

Histamine is a basic amine stored in mast cells, with its release capable of activating one of four histamine receptors. The histamine 3 receptor (HR) is known to be cardioprotective during acute ischemia by acting to limit norepinephrine release. However, a recent study reported that myofibroblasts isolated from the infarct zone of rat hearts responded to HR activation by up-regulating collagen production. Thus, it is necessary to clarify the potential role of the HR in relation to fibrosis in the heart. We identified that the mouse left ventricle (LV) expresses the HR. Isolation of mouse cardiac fibroblasts determined that while angiotensin II (Ang II) increased levels of the HR, these cells did not produce excess collagen in response to HR activation. Using the Ang II mouse model of adverse cardiac remodeling, we found that while HR blockade had little effect on cardiac fibrosis, activation of the HR reduced cardiac fibrosis and macrophage infiltration. These findings suggest that when activated, the HR is anti-inflammatory and anti-fibrotic in the mouse heart and may be a promising target for protecting against cardiac fibrosis.