Abstract 83: Intracerebroventricular Administration of Autologous Bone Marrow-derived Cells Attenuate Slow Pressor Angiotensin II Initiated Hypertension in Rats
Objectives: Subcutaneous infusion of non-pressor doses of angiotensin II (Ang II) gradually produces hypertension in part via central mechanism. Bone marrow-derived cells (BMC) have an ability to secrete paracrine factors leading to improvements in tissue injury. We hypothesized that implantation of autologous BMCs in the brain would attenuate Ang II initiated neurogenic hypertension via secreted paracrine factors.
METHODS: Sprague-Dawley rats were divided into following 4 groups: rats received vehicle infusion with intracerebroventricular (icv) administration of medium (V/M group, n=5); rats received vehicle infusion with icv administration of DiI labeled BMCs (V/B group, n=3); rats received Ang II infusion (150 ng/kg/min) with icv administration of medium (A/M group, n=4); rats received Ang II infusion with icv administration of BMCs (A/B group, n=5). Three weeks following initiation of the infusion, rats had surgery to implant arterial and venous catheters. Resting mean arterial pressure (MAP) of rats was recorded in conscious unrestrained state and resting sympathetic tone was evaluated with a peak depressor response produced by hexamethonium (C6) injection.
Results: Systolic blood pressure (SBP) measured by tailcuff method was similar among the groups, only A/M group had a trend to increase in SBP. Resting MAPs of V/M, V/B, A/M and A/B group were 125±2, 116±2, 174±7, 134±8 mmHg, respectively. Ang II infusion significantly increased MAP in A/M group, however in A/B group, icv administration of BMCs attenuated the Ang II mediated increase in MAP. Heart rate was similar among the groups. The peak depressor responses to C6 injection in V/M, V/B, A/M and A/B group were 38±3, 46±6, 77±5, 48±1 mmHg, respectively. Ang II infusion significantly increased the peak depressor response to C6 and icv administration of BMCs attenuated the increase in peak depressor response. DiI positive cells were distributed to the choroid plexus, surface of ventricle, and subventricular zone but not to the subfornical organ.
Conclusion: Icv administration of autologous BMCs attenuate slow pressor Ang II initiated hypertension via attenuating the Ang II mediated sympathetic activation in rats. Paracrine factors secreted from the BMCs may be involved in this process.
- © 2012 by American Heart Association, Inc.