Inhibition of the bradykinin B1 receptor attenuates blood pressure and cardiac hypertrophy in DOCA‐salt hypertensive mice (856.12)

Abstract

DOCA‐salt hypertension is associated with increased activity of the kallikrein‐kinin system. We sought to explore whether bradykinin B1 receptor (B1R)‐mediated inflammation contribute to DOCA‐salt hypertension. While baseline blood pressure (BP; telemetry) was not different, DOCA‐salt treatment (1 mg/g body weight DOCA, 1% NaCl for 28 d) resulted in significantly lower BP in B1R knockout mice (121 ±2 mmHg, n=5) compared to non‐transgenic (NT) mice (138 ±3 mmHg, n=8). In DOCA‐treated NT mice, B1R expression (Western blot) in the brain was increased by 2 fold (n=4, p<0.01). To dismiss potential developmental alterations in knockout mice, we complemented our study using a pharmacological approach with inhibition of B1R in the brain of NT mice. ICV infusion of R715, a specific B1R antagonist, attenuated the DOCA‐salt‐induced increase in BP in NT mice (125 ±3 mmHg, n=3, p<0.01). Cardiac hypertrophy was also attenuated in NT+R715 mice (HW/BW: 4.1 ±0.1 vs. 5.6 ±0.2; HW/tibia length: 7.9 ±0.3 vs. 9.2 ±0.7; p<0.01 vs. NT+DOCA). NT+DOCA mice had increased inflammation (qRT‐PCR), as shown by elevated gene expression of TNF, IL‐1β and IL‐6 (3‐, 8‐, and 5‐fold, respectively, n=9, p<0.01 vs. NT) in the hypothalamic paraventricular nucleus, which was attenuated in NT+R715 mice. Taken together, these data provide evidence that B1R contributes to neuroinflammation, thereby the development of DOCA‐salt hypertension.Grant Funding Source: Supported by AHA 12EIA8030004 and 13POST16500025