In this study, three key findings were revealed: (1) both AVP and aldosterone were involved in cardiac fibrosis and heart failure in post-infarction rats; (2) AVP was able to induce aldosterone secretion in CMECs by enhancing the expression of CYP11B2; and (3) AVP upregulated CYP11B2 expression through promoting the phosphorylation of CaMK and CREB after binding to the V1R. Here, CREB1 is linked to fibrosis.