Angiotensin II AT2 receptor activation attenuates AT1 receptor-induced increases in the glomerular filtration of albumin: a multiphoton microscopy study

Abstract

In this study, we assessed the acute effects of angiotensin II on the albumin glomerular sieving coefficient (GSC) using intravital microscopy. The experiments were performed on Munich Wistar Froemter (MWF) rats. Alexa-Fluor-594 albumin was injected intravenously, and the fluorescence intensity in the glomerular capillaries and Bowman's space was determined to calculate the albumin GSC. The GSC was measured before and during the constant infusion of angiotensin II (10 ng·min(-1)·kg(-1) body wt). Baseline mean arterial pressure (MAP) was 99 ± 5 mmHg and stabilized at 137 ± 5 mmHg during angiotensin II infusion. The baseline GSC averaged 0.00044 ± 4.8 × 10(-5) and increased by 286 ± 44% after angiotensin II infusion (P < 0.0001). The proximal tubular Alexa-Fluor-594 albumin uptake was enhanced during angiotensin II infusion (518% of the baseline value during angiotensin II vs. 218% in controls; P < 0.0001). No change in GSC was observed when the AT1 antagonist losartan was injected before the start of angiotensin II infusion. The AT2 antagonist PD123319 increased the baseline GSC from 0.00052 ± 3.6 × 10(-5) to 0.00074 ± 8.2 × 10(-5) (P = 0.02) without altering the MAP. During angiotensin II infusion with losartan, PD123319 increased the albumin GSC from 0.00037 ± 5.8 × 10(-5) to 0.00115 ± 0.00015 (P = 0.001). When the renal perfusion pressure was mechanically controlled, the GSC increased from 0.0007 ± 0.00019 to 0.0025 ± 0.00063 during angiotensin II infusion (P = 0.047), similar to what was observed when the renal perfusion pressure was allowed to increase. In summary, AT1 activation acutely increases the albumin GSC. This effect appears to be largely independent of changes in the renal perfusion pressure. The AT2 receptor partially attenuates the proteinuric effects of the AT1 receptor.

Keywords: AT receptors; angiotensin II; glomerular filtration barrier; mulitphoton microscopy; proteinuria.