Does the 'step' change methodology compared to 'dynamic' methods better assess renal autoregulatory capacity and susceptibility to hypertensive injury in renal mass reduction rat models?
The step methodology, but not dynamic methods, provides a valid index of underlying susceptibility to hypertensive glomerular damage after renal mass reduction in rats.
Renal autoregulatory (AR) mechanisms provide the primary protection against transmission of systemic pressures, and their impairment is believed to be responsible for the enhanced susceptibility to hypertensive renal damage in renal mass reduction (RMR) models. Assessment of AR capacity by the "step" change methodology under anesthesia was compared with that by "dynamic" methods in separate conscious control Sprague-Dawley rats and after uninephrectomy (UNX) and (3/4) RMR (RK-NX) (n = 7-10/group). Substantially less AR capacity was seen by the dynamic vs. the step methodology in control rats. Moreover, dynamic AR capacity did not differ among controls, UNX, and RK-NX rats (fractional gain in admittance approximately 0.4-0.5 in all groups at frequencies in the range of 0.0025-0.025 Hz). By contrast, significant impairment of step AR was seen in RK-NX vs. control or UNX rats (AR indexes 0.7 +/- 0.1 vs. 0.1 +/- 0.02 and 0.2 +/- 0.04, respectively, P < 0.01). We propose that the step and dynamic methods evaluate the renal AR responses to different components of blood pressure (BP) power with the step AR assessing the ability to buffer large changes in average BP (DC power), whereas the present "dynamic" methods assess the AR ability to buffer slow BP fluctuations (<0.25 Hz) superimposed on the average BP (AC power), a substantially smaller component of total BP power. We further suggest that step but not dynamic AR methods as presently performed provide a valid index of the underlying susceptibility to hypertensive glomerular damage after RMR.
Bidani et al. (Tue,) studied this question.