Dose-dependent actions and temporal effects of angiotensin II on microvascular permeability.

Background: Angiotensin II is a potent vasoconstrictor that is elevated after shock. Previous studies suggest that angiotensin II may directly modulate the endothelial barrier. Our hypothesis was that angiotensin II would increase microvascular hydraulic permeability in a dose-dependent fashion.
Methods: Hydraulic permeability (Lp) is a measure of water flow across the endothelial barrier. Lp was measured in rat mesenteric venules using the modified Landis micro-occlusion technique. Venules were first perfused with Ringer's solution and baseline measurements of Lp were obtained. The venules were then recannulated and perfused with angiotensin II at 0.2 ng/mL (n = 5), 2.0 ng/mL (n = 5), 20 ng/mL (n = 8), and 200 ng/mL (n = 5), before final Lp measurements.
Results: Baseline values for Lp averaged 1.35 +/- 0.12. The 20-ng/mL and 200-ng/mL concentrations of angiotensin II significantly increased Lp to 3.86 +/- 0.4 (p < 0.0008) and 7.94 +/- 1.1 (p < 0.005), respectively. The maximal effect of angiotensin II was seen at 15 minutes of perfusion. Units for Lp are x 10(-7) cm.s-1.cm H2O-1.
Conclusion: Angiotensin II affects a dose-dependent increase in microvascular permeability. This suggests that angiotensin II is involved in modulating intravascular fluid flux across the vessel wall. This effect is opposite to that observed in other vasoconstrictors that are up-regulated after trauma.