Angiotensin II AT 2 receptor activation attenuates AT 1 receptor - induced increases in the 1 glomerular filtration of albumin – a multiphoton microscopy study

25 In this study, we assessed the acute effects of angiotensin II on the albumin glomerular 26 sieving coefficient (GSC) using intravital microscopy. The experiments were performed on 27 Munich Wistar Froemter (MWF) rats. Alexa-Fluor-594 albumin was injected intravenously, 28 and the fluorescence intensity in the glomerular capillaries and Bowman’s space was 29 determined to calculate the albumin GSC. The GSC was measured before and during the 30 constant infusion of angiotensin II (10 ng/min/kg BW). Baseline mean arterial pressure 31 (MAP) was 99±5 mm Hg and stabilized at 137±5 mm Hg during angiotensin II infusion. The 32 baseline GSC averaged 0.00044±4.8*10 and increased by 286±44% after angiotensin II 33 infusion (p<.0001). The proximal tubular Alexa-Fluor-594 albumin uptake was enhanced 34 during angiotensin II infusion (518% of the baseline value during angiotensin II vs. 218% in 35 controls; p<.0001). No change in GSC was observed when the AT1 antagonist losartan was 36 injected before the start of angiotensin II infusion. The AT2 antagonist PD123319 increased 37 the baseline GSC from 0.00052±3.6*10 to 0.00074±8.2*10 (p=.02) without altering the 38 MAP. During angiotensin II infusion with losartan, PD123319 increased the albumin GSC 39 from 0.00037±5.8*10 to 0.00115±.00015 (p=.001). When the renal perfusion pressure was 40 mechanically controlled, the GSC increased from 0.0007±.00019 to 0.0025±.00063 during 41 angiotensin II infusion (p=.047), similar to what was observed when the renal perfusion 42 pressure was allowed to increase. In summary, AT1 activation acutely increases the albumin 43 GSC. This effect appears to be largely independent of changes in the renal perfusion pressure. 44 The AT2 receptor partially attenuates the proteinuric effects of the AT1 receptor. 45