Anil K Bidani1,2, Aaron J Polichnowski3,4, Hector Licea-Vargas3, Jianrui Long5, Stephanie Kliethermes6, Geoffrey A Williamson5, Karen A Griffin3,2. 1. Division of Nephrology, Department of Medicine, Loyola University Medical Center and abidani@lumc.edu. 2. Renal Section, Department of Medicine, Edward Hines Jr. Veterans Administration Hospital, Maywood, Illinois. 3. Division of Nephrology, Department of Medicine, Loyola University Medical Center and. 4. Department of Biomedical Sciences and Center of Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee. 5. Department of Electrical and Computer Engineering, Illinois Institute of Technology, Chicago, Illinois; and. 6. Department of Orthopedics and Rehabilitation, University of Wisconsin, Madison, Wisconsin.
Abstract
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.
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.
Authors: Elke Wühl; Antonella Trivelli; Stefano Picca; Mieczyslaw Litwin; Amira Peco-Antic; Aleksandra Zurowska; Sara Testa; Augustina Jankauskiene; Sevinc Emre; Alberto Caldas-Afonso; Ali Anarat; Patrick Niaudet; Sevgi Mir; Aysin Bakkaloglu; Barbara Enke; Giovanni Montini; Ann-Margret Wingen; Peter Sallay; Nikola Jeck; Ulla Berg; Salim Caliskan; Simone Wygoda; Katharina Hohbach-Hohenfellner; Jiri Dusek; Tomasz Urasinski; Klaus Arbeiter; Thomas Neuhaus; Jutta Gellermann; Dorota Drozdz; Michel Fischbach; Kristina Möller; Marianne Wigger; Licia Peruzzi; Otto Mehls; Franz Schaefer Journal: N Engl J Med Date: 2009-10-22 Impact factor: 91.245
Authors: Aaron J Polichnowski; Karen A Griffin; Hector Licea-Vargas; Rongpei Lan; Maria M Picken; Jainrui Long; Geoffrey A Williamson; Christian Rosenberger; Susanne Mathia; Manjeri A Venkatachalam; Anil K Bidani Journal: Am J Physiol Renal Physiol Date: 2020-03-16
Authors: Jacqueline C Potter; Shannon A Whiles; Conor B Miles; Jenna B Whiles; Mark A Mitchell; Brianna E Biederman; Febronia M Dawoud; Kevin F Breuel; Geoffrey A Williamson; Maria M Picken; Aaron J Polichnowski Journal: J Am Heart Assoc Date: 2021-10-23 Impact factor: 5.501