title: Modulation of the myogenic mechanism: concordant effects of NO synthesis inhibition and O2- dismutation on renal autoregulation in the time and frequency domains.
abstract: Renal blood flow autoregulation was investigated in anesthetized C57Bl6 mice using time- and frequency-domain analyses. Autoregulation was reestablished by 15 s in two stages after a 25-mmHg step increase in renal perfusion pressure (RPP). The renal vascular resistance (RVR) response did not include a contribution from the macula densa tubuloglomerular feedback mechanism. Inhibition of nitric oxide (NO) synthase [N(G)-nitro-l-arginine methyl ester (l-NAME)] reduced the time for complete autoregulation to 2 s and induced 0.25-Hz oscillations in RVR. Quenching of superoxide (SOD mimetic tempol) during l-NAME normalized the speed and strength of stage 1 of the RVR increase and abolished oscillations. The slope of stage 2 was unaffected by l-NAME or tempol. These effects of l-NAME and tempol were evaluated in the frequency domain during random fluctuations in RPP. NO synthase inhibition amplified the resonance peak in admittance gain at 0.25 Hz and markedly increased the gain slope at the upper myogenic frequency range (0.06-0.25 Hz, identified as stage 1), with reversal by tempol. The slope of admittance gain in the lower half of the myogenic frequency range (equated with stage 2) was not affected by l-NAME or tempol. Our data show that the myogenic mechanism alone can achieve complete renal blood flow autoregulation in the mouse kidney following a step increase in RPP. They suggest also that the principal inhibitory action of NO is quenching of superoxide, which otherwise potentiates dynamic components of the myogenic constriction in vivo. This primarily involves the first stage of a two-stage myogenic response.
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Moss
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Tayler K
authors.initials: TK
authors.lastname: Gentle
authors.affiliation: Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina arends@med.unc.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Arendshorst
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009130:Muscle, Smooth / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012079:Renal Circulation / Q000187:drug effects; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism*; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D013113:Spin Labels; D001127:Arginine Vasopressin; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester
keywords: admittance gain; afferent arteriole; perfusion pressure; renal circulation; renal vascular resistance
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