BP Fluctuations and the Real-Time Dynamics of Renal Blood Flow Responses in Conscious Rats
Authors: Bidani Anil K. , Polichnowski Aaron J. , Licea-Vargas Hector , Long Jianrui , Kliethermes Stephanie , Williamson Geoffrey A. , Griffin Karen A. 
Published: December 2019

Significance Statement
Real-time dynamics of renal autoregulation to stabilize renal blood flow and GFR and protect glomeruli from hypertension in conscious animals with spontaneously fluctuating BP remain uncharacterized. Using novel methods to analyze relationships between BP and renal blood flow, the authors show that conscious rats display autoregulatory restoration of renal blood flow in <10 seconds; restoration is significantly slower with impaired autoregulation, resulting in exposure to increased glomerular pressure. However, unlike rats under anesthesia, conscious rats achieve complete compensation, even with severe autoregulatory impairment after calcium channel blockade. These data indicate that transient glomerular pressure elevations may play a larger role in hypertensive glomerulosclerosis than recognized, and suggest that mechanisms independent of voltage-gated calcium channels might maintain overall renal blood flow and GFR stability when known autoregulatory mechanisms are impaired.

Background
Renal autoregulation maintains stable renal function despite BP fluctuations and protects glomerular capillaries from hypertensive injury. However, real-time dynamics of renal autoregulation in conscious animals have not been characterized.

Methods
To develop novel analytic methods for assessing renal autoregulation, we recorded concurrent BP and renal blood flow in conscious rats, comparing animals with renal autoregulation that was intact versus impaired (from 3/4 nephrectomy), before and after additional impairment (from the calcium channel blocker amlodipine). We calculated autoregulatory indices for adjacent short segments of increasing length (0.5, 1, 2.5, 5, 10, and 20 seconds) that exhibited a mean BP difference of at least 5 mm Hg.

Results
Autoregulatory restoration of renal blood flow to baseline after BP changes in conscious rats occurs rapidly, in 5–10 seconds. The response is significantly slower in states of impaired renal autoregulation, enhancing glomerular pressure exposure. However, in rats with severe renal autoregulation impairment (3/4 nephrectomy plus amlodipine), renal blood flow in conscious animals (but not anesthetized animals) was still restored to baseline, but took longer (15–20 seconds). Consequently, the ability to maintain overall renal blood flow stability is not compromised in conscious rats with impaired renal autoregulation.

Conclusions
These novel findings show the feasibility of renal autoregulation assessment in conscious animals with spontaneous BP fluctuations and indicate that transient increases in glomerular pressure may play a greater role in the pathogenesis of hypertensive glomerulosclerosis than previously thought. These data also show that unidentified mechanosensitive mechanisms independent of known renal autoregulation mechanisms and voltage-gated calcium channels can maintain overall renal blood flow and GFR stability despite severely impaired renal autoregulation.