Intracerebroventricular administration of bone marrow-derived cells attenuates angiotensin II-initiated neurogenic hypertension in rats.

Abstract

Bone marrow-derived cells exert anti-inflammatory actions and can migrate into the brain. However, their role in the development of neurogenic hypertension remains unclear. A hyperactive renin-angiotensin system and inflammation in the brain are mechanisms that contribute to angiotensin II-initiated neurogenic hypertension. We hypothesized that bone marrow-derived cells in the brain attenuate the overactive brain renin-angiotensin system and inflammation, thereby reducing neurogenic hypertension. We cultured plastic-adherent bone marrow-derived cells for 3 weeks. Seven days after initiation of vehicle or angiotensin II infusions, the rats underwent intracerebroventricular administration of either serum-free medium or autologous bone marrow-derived cells (106 cells). After 23 days of infusion, the mean arterial pressure was recorded, and the sympathetic tone was evaluated. Rats infused with angiotensin II demonstrated significant increases in the resting mean arterial pressure and the peak depressor response to ganglionic blockade (vehicle vs. angiotensin II infusion, 119 ± 4 vs. 178 ± 6 mmHg and -34 ± 6 vs. -74 ± 5 mmHg, respectively). Intracerebroventricularly administered bone marrow-derived cells attenuated the angiotensin II-mediated increases in the resting mean arterial pressure and peak depressor response (142 ± 11 and -52 ± 4 mmHg, respectively). The cells also reduced the angiotensin II-induced increases in angiotensin II type 1 receptor and transforming growth factor-β expression in the brain. In conclusion, bone marrow-derived cells in the brain may have a protective role against the development of angiotensin II-induced neurogenic hypertension by modulating angiotensin II type 1 receptor expression and inflammatory processes.