Renal blood flow and dynamic autoregulation in conscious mice

Abstract

Autoregulation of renal blood flow (RBF) occurs via myogenic and tubuloglomerular feedback (TGF) mechanisms that are engaged by pressure changes within preglomerular arteries and by tubular flow and content, respectively. Our understanding of autoregulatory function in the kidney largely stems from experiments in anesthetized animals where renal perfusion pressure is precisely controlled. However, normally occurring variations in blood pressure are sufficient to engage both myogenic and TGF mechanisms, making the assessment of autoregulatory function in conscious animals of significant value. To our knowledge, no studies have evaluated the dynamics of RBF in conscious mice. Therefore, we used spectral analysis of blood pressure and RBF and identified dynamic operational characteristics of the myogenic and TGF mechanisms in conscious, freely moving mice instrumented with ultrasound flow probes and arterial catheters. The myogenic response generates a distinct resonance peak in transfer gain at 0.31 +/- 0.01 Hz. Myogenic-dependent attenuation of RBF oscillations, indicative of active autoregulation, is apparent as a trough in gain below 0.3 Hz (-6.5 +/- 1.3 dB) and a strong positive phase peak (93 +/- 9 deg), which are abolished by amlodipine infusion. Operation of TGF produces a local maximum in gain at 0.05 +/- 0.01 Hz and a positive phase peak (62.3 +/- 12.3 deg), both of which are eliminated by infusion of furosemide. Administration of amlodipine eliminated both myogenic and TGF signature peaks, whereas furosemide shifted the myogenic phase peak to a slower operational frequency. These data indicate that myogenic and TGF dynamics may be used to investigate the effectiveness of renal autoregulatory mechanisms in conscious mice.