title: ANG II-induced downregulation of RBF after a prolonged reduction of renal perfusion pressure is due to pre- and postglomerular constriction.
abstract: Previous experiments from our laboratory showed that longer-lasting reductions in renal perfusion pressure (RPP) are associated with a gradual decrease in renal blood flow (RBF) that can be abolished by clamping plasma ANG II concentration ([ANG II]). The aim of the present study was to investigate the mechanisms behind the RBF downregulation in halothane-anesthetized Sprague-Dawley rats during a 30-min reduction in RPP to 88 mmHg. During the 30 min of reduced RPP we also measured glomerular filtration rate (GFR), proximal tubular pressure (P(prox)), and proximal tubular flow rate (Q(LP)). Early distal tubular fluid conductivity was measured as an estimate of early distal [NaCl] ([NaCl](ED)), and changes in plasma renin concentration (PRC) over time were measured. During 30 min of reduced RPP, RBF decreased gradually from 6.5 +/- 0.3 to 6.0 +/- 0.3 ml/min after 5 min (NS) to 5.2 +/- 0.2 ml/min after 30 min (P < 0.05). This decrease occurred in parallel with a gradual increase in PRC from 38.2 +/- 11.0 x 10(-5) to 87.1 +/- 25.1 x 10(-5) Goldblatt units (GU)/ml after 5 min (P < 0.05) to 158.5 +/- 42.9 x 10(-5) GU/ml after 30 min (P < 0.01). GFR, P(prox), and [NaCl](ED) all decreased significantly after 5 min and remained low. Estimates of pre- and postglomerular resistances showed that the autoregulatory mechanisms initially dilated preglomerular vessels to maintain RBF and GFR. However, after 30 min of reduced RPP, both pre- and postglomerular resistance had increased. We conclude that the decrease in RBF over time is caused by increases in both pre- and postglomerular resistance due to rising plasma renin and ANG II concentrations.
authors.affiliation: Dept. of Medical Physiology, The Panum Institute, 10.5, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. cmehlin@mfi.ku.dk
authors.forename: Charlotte Mehlin
authors.initials: CM
authors.lastname: Sorensen
authors.forename: Paul Peter
authors.initials: PP
authors.lastname: Leyssac
authors.forename: Max
authors.initials: M
authors.lastname: Salomonsson
authors.forename: Ole
authors.initials: O
authors.lastname: Skott
authors.forename: Niels-Henrik
authors.initials: NH
authors.lastname: Holstein-Rathlou
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000502:physiology; D008297:Male; D008954:Models, Biological; D009399:Nephrons / Q000502:physiology; D011188:Potassium / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D012965:Sodium Chloride / Q000097:blood; D014655:Vascular Resistance / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
chemical_list: D014662:Vasoconstrictor Agents; D014867:Water; D000804:Angiotensin II; D012965:Sodium Chloride; D011188:Potassium