The dopamine D3 receptor knockout mouse models aging‐related changes in hypertension and cardiac fibrosis

The increased prevalence of hypertension with aging is well established, as is a role for the dopamine D3 receptor in the general pathophysiology of hypertension. To determine the specific effects of D3 dysfunction on autonomic output and cardiac involvement in aging associated hypertension, non‐invasive blood pressure measurements, echocardiography, and histochemistry were used to compare cardiac structure and function in differently‐aged wild‐type (WT) animals (10 weeks, 1 year, 2 year) and D3 receptor knockout mice (D3KO). In WT animals, aging‐related increases in blood pressure and cardiac function, accompanied by bradycardia in the oldest animals were observed. Intriguingly, 2 month‐old D3KO mice displayed blood pressure and heart rate values that were significantly increased over their age‐matched WT controls, and that were comparable to those of the 2 year‐old WT group. Echocardiography did not reveal significant differences between age matched young WT and D3KO mice, but immunohistology demonstrated fibrosis in the young D3KO mice that was comparable to the age‐related fibrosis seen in 2 year old WT mice. Taken together, these data suggest that the D3KO animal may serve as a model to better understand the role of the dopamine D3 receptor in the aging heart, and in particular its role in the pathophysiology of cardiovascular fibrosis. Funded by Brody School of Medicine (SC), and NIH NHLBI HL081720 (DAT).