(726.7) Real-Time dynamics of renal autoregulatory responses to BP changes in conscious, normotensive and hypertensive rat strains

Poster Board Number: E190

Karen Griffin (Hines VA Hospital and Loyola University Medical Center), Aaron Polichnowski (East Tennessee State University), Geoffrey Williamson (Illinois Institute of Technology), Anil Bidani (Hines VA Hospital and Loyola University Medical Center)

Renal autoregulatory (AR) mechanisms are believed to insulate RBF and GFR from the continuously fluctuating systemic pressures and protect the glomerular capillaries from barotrauma by preventing glomerular transmission of systemic hypertension.  However, renal AR has usually only been assessed by the degree to which RBF is restored to baseline after step changes in BP are imposed, generally under anesthesia.  AR indices (% changes in RBF / % changes in BP) are used to quantitate the magnitude of the AR compensation.  However, such methods do not provide an assessment of the real time dynamics of AR responses to the spontaneously occurring BP fluctuations in real time.  We have recently described novel analytic methods to characterize both the magnitude and the kinetics of such AR responses to BP fluctuations in conscious Sprague-Dawley rats with intact (controls) and impaired AR (3/4 nephrectomy) and/or calcium channel blockade (JASN 31(2):324-336, 2020).  Essentially, AR indices were calculated for adjacent segments of varying lengths (0.5 – 20 sec) which exhibited a MAP difference of at least 5 mmHg.  These studies indicated a much greater rapidity of the normal AR response than observed using standard methods under anesthesia with the bulk of AR compensation (gt;50%) occurring within 2.5 sec with complete compensation occurring more slowly by ~10 sec.  This rapid initial and likely myogenic component of the response was noted to be significantly slower in states of impaired renal AR with lt;40% of AR compensation being achieved by 5 sec.  To assess the generalizability of these pattern of AR responses and interpretations of rapid myogenic protection, similar AR analysis were performed on concurrent BP and RBF recordings of 1-4 hr duration that had been obtained in conscious chronically instrumented hypertensive and normotensive rat strains in our laboratory for transfer function analysis in control SHR, SHRsp, Dahl S (DS) and R (DR) rats, and Sprague-Dawley (SD) rats over the past 20 years (Fig. 1).  The pattern of AR responses and compensation is remarkably similar in all rat strains except that the responses are even faster and stronger in hypertensive rats with ~80% compensation being achieved by 2.5 sec (Fig. 2).  To further examine the impact of ambient BP on AR responses, AI were separately calculated when the ambient MAP was within 30 mmHg below (low BP) or above (high BP) the average MAP during the recordings for each strain.  There was a clear trend for the AR responses to be stronger at higher ambient MAP, although statistical significance was not achieved in all strains because of the scatter in individual animal data (Fig. 3).  These data suggest that in addition to genetic factors, ambient BP per se may modulate the dynamics of protective renal AR responses in conscious rats.



Figures 1-3