title: Renal interstitial fluid ATP responses to arterial pressure and tubuloglomerular feedback activation during calcium channel blockade.
abstract: A close relationship between changes in renal interstitial fluid (RIF) ATP concentrations and renal autoregulatory or tubuloglomerular feedback (TGF)-dependent changes in renal vascular resistance (RVR) has been demonstrated, but it has not been determined whether the changes in RIF ATP are a consequence or the cause of the changes in RVR. The present study was performed in anesthetized dogs to assess the changes in RIF ATP following changes in renal arterial pressure (RAP) or stimulation of the TGF mechanism under conditions where changes in RVR were prevented by nifedipine, a calcium channel blocker. RIF ATP levels were measured by using microdialysis probes. Intra-arterial infusion of nifedipine (0.36 microg x kg(-1) x min(-1)) increased renal blood flow (RBF: from 4.49 +/- 0.27 to 5.34 +/- 0.39 ml x min(-1) x g(-1)) and glomerular filtration rate (GFR: from 0.84 +/- 0.07 to 1.09 +/- 0.11 ml x min(-1) x g(-1)). Under conditions of nifedipine infusion, autoregulatory adjustments in RBF, GFR, and RVR were not observed during stepwise reductions in RAP within the autoregulatory range (from 135 +/- 7 to 76 +/- 1 mmHg, n = 7). Furthermore, stimulation of the TGF mechanism with intra-arterial infusion of acetazolamide (100 microg x kg(-1) x min(-1)) did not alter RBF, GFR, and RVR (n = 7). During treatment with nifedipine, RIF ATP levels were significantly decreased in response to reductions in RAP (10.7 +/- 0.7, 5.8 +/- 0.7 and 2.8 +/- 0.3 nmol/l at 135 +/- 7, 101 +/- 4, and 76 +/- 1 mmHg, n = 7) and increased by acetazolamide infusion (from 8.8 +/- 0.8 to 17.0 +/- 1.8 nmol/l, n = 7). These results are similar to those that occurred in dogs not treated with nifedipine and thus demonstrate that the changes in RIF ATP can occur in the absence of autoregulatory or TGF-mediated changes in RVR. The data provide further support to the hypothesis that RIF ATP contributes to adjustments in RVR associated with renal autoregulation and changes in activity of the TGF mechanism.
authors.affiliation: Department of Physiology, Tulane University Health Sciences Center, New Orleans, Louisiana, USA. akira@kms.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Keith E
authors.initials: KE
authors.lastname: Jackson
authors.forename: Dewan S A
authors.initials: DS
authors.lastname: Majid
authors.forename: Matlubur
authors.initials: M
authors.lastname: Rahman
authors.forename: L Gabriel
authors.initials: LG
authors.lastname: Navar
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004285:Dogs; D045604:Extracellular Fluid / Q000378:metabolism*; D025461:Feedback, Physiological; D007668:Kidney / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000502:physiology*; D007684:Kidney Tubules / Q000502:physiology*; D017551:Microdialysis; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D000255:Adenosine Triphosphate; D009543:Nifedipine