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