Antiproteinuric effects of ACE inhibitors have classically been assigned to their hemodynamic effects. Here we assess the acute effects of angiotensin II (AngII) on albumin glomerular sieving coefficient (GSC) in young anesthetized Munich Wister Froemter rats using intravital microscopy.

Methods:

Purified Alexa-Fluor-594 albumin was injected i.v. and fluorescence intensities were determined in glomerular capillaries and in Bowman's space (BS) of several superficial glomeruli. The albumin GSC was then calculated according to: GSC = (intensity BS - intensity background)/(intensity capillaries - intensity background). GSC was measured before and during constant infusion of Ang II (27 ng/min/g BW), while mean arterial blood pressure (MAP) was monitored during the entire experiment.

Results:

Baseline MAP averaged 90±4 mm Hg and stabilized at 130+/-11 mm Hg during AngII infusion. Capillary flow velocity was markedly reduced during AngII infusion (figure1). Albumin GSC averaged 0.00038+/-.00009 at baseline and increased by 263+/-34% within 10 min after constant AngII infusion. During AngII infusion, de novo fluorescence was observed in the proximal tubules indicating uptake of filtered Alexa-albumin. These effects were abolished when a bolus of the AT1 antagonist losartan (9.9 µg/g BW) was injected prior to AngII. In control experiments (saline infusion) no significant changes in MAP, GSC or tubular fluorescence were observed.

Conclusions:

AngII causes rapid increases in glomerular albumin filtration, which are presumably mediated by angiotensin AT1 receptors.

Figure 1