Dynamic renal autoregulation in conscious, freely moving mice

Abstract

Myogenic (MYO) and tubuloglomerular feedback (TGF) mechanisms control renal blood flow (RBF) autoregulation. MYO and TGF operate with specific dynamic properties to regulate RBF in response to spontaneous fluctuations in blood pressure (BP). Developing a method to evaluate MYO and TGF control systems in conscious mice would allow RBF autoregulation to be studied in available genetic models. Using spectral analysis of BP and RBF, we identified dynamic operational characteristics of MYO and TGF in conscious, freely moving mice (NZW, n=10), instrumented with ultrasound flow probes and arterial catheters. We found that MYO generates a distinct resonance peak in transfer gain at 0.31±0.01 Hz. MYO‐dependent attenuation of RBF oscillations, indicative of active autoregulation, is apparent as a trough in gain below 0.3 Hz (−6.3±1.5 dB) and a strong positive phase peak (87±8 deg), which are abolished by amlodipine infusion (3.3±1.1 dB p<0.01; 14±1 deg p<0.01). Operation of TGF produces a local maximum in gain at 0.77±0.8 Hz and a positive phase peak (60.4±14.3 deg), both of which are removed by infusion of furosemide. Administration of amlodipine eliminated both MYO and TGF signature peaks, whereas furosemide did not alter MYO operational characteristics. These data indicate that MYO and TGF dynamics may be used to investigate the effectiveness of renal autoregulatory mechanisms in conscious mice. (Supported by R01HL085907 MJR, R01HL069194 JFR)