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1 Department of Internal Medicine, Loyola University Medical Center and Edward Hines VA Hospital, Maywood, IL, USA
2 Department of Electrical and Computer Engineering, Illinois Institute of Technology, Chicago, IL, USA
3 Department of Pharmacology & Therapeutics, University of Calgary, Calgary, Alberta, Canada
* To whom correspondence should be addressed. E-mail: kgriffi{at}lumc.edu.
Renal autoregulation (AR) mechanisms provide the primary protection against transmission of systemic pressures and hypertensive renal damage. However, the relative merits of the 'step' change vs. 'dynamic' methods for the assessment of AR capacity remain controversial. The effects of 48-72 hours of orally administered amlodipine ('L' type) and mibefradil ('T' type) calcium channel blockers (CCBs) on 'step' and 'dynamic' AR in Sprague- Dawley rats were compared. Both CCBs significantly impaired 'steady-state step' AR (autoregulatory indices = ~0.5 vs. ~0.1 in controls, p < 0.05; n=9-10/group). By contrast, dynamic AR compensation in separate conscious rats (n=12) was not significantly altered by either amlodipine (n=10) or mibefradil (n=6) (fractional gain in admittance ~0.4-0.5 in all groups at frequencies in the range of 0.0025 - 0.025 Hz). However, both CCBs tended to attenuate the myogenic resonance peak along with shifting it to a significantly slower frequency (p < 0.001) during 'dynamic' AR but no consistent effects were observed on the TGF resonance peak. While the reasons for the insensitivity of 'dynamic' vs. 'steady-state step' AR capacity estimates to CCBs remain to be established, the present data indicates that 'dynamic' AR methods may have a limited utility for assessing AR capacity, but may provide potentially important insights into the operational characteristics of AR control mechanisms. A strong correlation was also observed between the average conductance and the admittance gain at the heart beat frequency (r = 0.77, p < 0.001) suggesting that such parameters may provide additional and possibly more meaningful indices of BP transmission in conscious animals during 'dynamic' AR.
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