Angiotensin II induced down regulation of RBF after a prolonged reduction of renal perfusion pressure is due to pre- and postglomerular constriction

Previous experiments from our laboratory have shown 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 angiotensin II concentration ([Ang II]). The aim of the present study was to investigate the mechanisms behind the RBF downregulation in halothaneanaesthetized Sprague Dawley rats during a 30 min reduction in RPP to 88 mm Hg. During the 30 min of reduced RPP we also measured glomerular filtration rate (GFR), proximal tubular pressure (Pprox) and proximal tubular flow rate (QLP). 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 ml/min 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 plasma renin concentration from 38.2 ± 11.0 x 10 GU/ml to 87.1 ± 25.1 x 10 GU/ml after 5 min (P < 0.05) to 158.5 ± 42.9 x 10 GU/ml after 30 min (P < 0.01). GFR, Pprox, and [NaCl]ED all decreased significantly after 5 min and remained low. Estimates of preand postglomerular resistances showed that the autoregulatory mechanisms initially dilated preglomerular vessels to maintain RBF and GFR. However, after 30 min of reduced RPP both preand postglomerular resistance had increased. We conclude that the decrease in RBF over time is caused by increases in both preand postglomerular resistance due to rising plasma renin and Ang II concentrations.