Abstract 093: Tubuloglomerular feedback system dynamically regulates cardiorenal crosstalk

The kidney auto-regulates its blood flow through myogenic response and the tubulo-glomerular feedback (TGF) system. TGF sustains oscillatory fluid flow in the kidney with a signature frequency at 0.03Hz, which is detectable across scales: at the single-nephron (via micro-puncture and intravital imaging), at the multi-nephron (via resting state magnetic resonance imaging) and at the whole-kidney (via transdermal measurement of renal clearance) levels. TGF is closely linked to the renin-angiotensin system (RAS) at the juxtaglomerular apparatus, potentially impacting systemic blood pressure regulation. Hypothesis: We hypothesize that oscillatory fluid flow in the kidney is coupled to arterial blood pressure fluctuation to achieve dynamic physiological control, which manifests differently in male and female subjects and is impaired in hypertension. Methods: We analyzed simultaneous telemetry-based measurements of arterial blood pressure (BP) and renal blood flow (RBF) in male and female Wistar Kyoto / Sprague-Dawley rats, under anesthesia or conscious. Power spectrum analysis was used to evaluate the temporal relationship between systemic BP and RBF with or without RAS inhibition with ACE inhibitor captopril. Results: Band-pass filtering-based smoothing revealed robust oscillations in arterial BP (with an amplitude of up to 25mmHg) and in RBF within the TGF frequency range in normotensive rats, where male rats exhibit higher frequency (median: 0.04Hz, n=5) than females (median: 0.02Hz, n=5), in both anesthetized and conscious measurements. Cross-plots of paired data uncovered a nonlinear relationship between arterial BP and RBF, indicating TGF as an effective mechanism to buffer BP changes, and that systemic BP is modulated with TGF. ACE inhibition increased the power of TGF frequency, where mixed-mode oscillations were observed in male rats, reminiscent of single-nephron GFR power spectrum seen in spontaneous hypertensive rats, but not in females. Conclusions: Here, we report an intricate relationship between systemic BP and RBF that is highly dynamic and mediated through the TGF system. We note male-female differences in TGF frequency distribution, as previously observed in single-nephron fluid flow measured by intravital two-photon imaging, as well as in responses to RAS inhibition. This work encourages further examination of cardiorenal crosstalk in hypertensive conditions.