title: The renin-angiotensin system and the third mechanism of renal blood flow autoregulation.
abstract: Autoregulation of renal blood flow comprises three mechanisms: the myogenic response (MR), the tubuloglomerular feedback (TGF), and a third mechanism (3M). The nature of 3M is unknown; it may be related to hypotensive resetting of autoregulation that probably relies on pressure-dependent stimulation of the renin-angiotensin system (RAS). Thus we used a normotensive angiotensin II clamp in anesthetized rats and studied autoregulation 1) by slow ramp-shaped reductions in renal perfusion pressure (RPP) followed by ramp-shaped RPP restorations and 2) by means of the step response technique: after 30 s of either total or partial suprarenal aortic occlusion, a step increase in RPP was made and the response of renal vascular conductance analyzed to assess the mechanisms' strength and initial direction (vasodilation or constriction). The angiotensin clamp abolished the resetting of autoregulation during ramp-shaped RPP changes. Under control conditions, the initial TGF response was dilatory after total occlusions but constrictive after partial occlusions. The initial 3M response presented a mirror image to the TGF: it was constrictive after total but dilatory after partial occlusions. The angiotensin clamp suppressed the TGF and turned the initial 3M response following total occlusions into dilation. We conclude that 1) pressure-dependent RAS stimulation is a major cause behind hypotensive resetting of autoregulation, 2) TGF sensitivity strongly depends on pressure-dependent changes in RAS activity, 3) the 3M is modulated, but not mediated, by the RAS, and 4) the 3M acts as a counterbalance to the TGF and might possibly be related to the recently described connecting tubule glomerular feedback.
authors.affiliation: Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, CCM, Tucholskystr. 2, D-10117 Berlin, Germany. erdmann.seeliger@charite.de
authors.forename: Erdmann
authors.initials: E
authors.lastname: Seeliger
authors.forename: Thomas
authors.initials: T
authors.lastname: Wronski
authors.forename: Mechthild
authors.initials: M
authors.lastname: Ladwig
authors.forename: Leszek
authors.initials: L
authors.lastname: Dobrowolski
authors.forename: Torsten
authors.initials: T
authors.lastname: Vogel
authors.forename: Michael
authors.initials: M
authors.lastname: Godes
authors.forename: Pontus B
authors.initials: PB
authors.lastname: Persson
authors.forename: Bert
authors.initials: B
authors.lastname: Flemming