In response to histamine, H2R activation leads to adenylyl cyclase-mediated cAMP activation, which can stimulate renin release in the kidney, induces positive inotropic and chronotropic responses of the heart [3,4,5], and this closely relates to the development of various cardiovascular diseases, such as myocardial ischemia and infarction, hypertension, and heart failure [15]. The gene discussed is REN; the disease is heart failure.