Angiotensin II effect on hydraulic permeability: interaction with endothelin-1, nitric oxide, and platelet activating...

The purposes of this study were: 1) to examine the influence of endothelin (ET-1) release on the ability of angiotensin (Ang) II to modulate permeability, 2) to determine if the action of Ang II on microvascular permeability is dependent on nitric oxide (NO) release, and 3) to explore the effect of Ang II in microvessels activated with platelet activating factor (PAF).

Hydraulic permeability (L(p)) was measured using the modified Landis in vivo micro occlusion technique during perfusion with: 1) the ET-1 receptor antagonist PD145065 (50 microM), then PD145065 + Ang II, 2) Ang II (20 nm), a NO synthase inhibitor L-NAME (100 microM), then L-NAME + Ang II, and 3) after endothelial activation with 10 nM of PAF, then PAF + Ang II.

1) The ET-1 antagonist increased L(p) 2.5-fold, Ang II alone increased L(p) five-fold, while Ang II perfusion during ET-1 antagonism increased L(p) over 6-fold (P < 0.04); 2) L-NAME increased L(p) over 3-fold. Ang II perfusion during NO synthase inhibition had no effect compared to NO synthase inhibition alone (P = 0.9) while Ang II alone increased L(p) 5-fold (P < or = 0.01); 3) PAF + Ang II (L(p) = 2.74 +/- 0.12) was decreased versus PAF alone (L(p) = 4.66 +/- 0.25) (P < 0.02).

Ang II does not increase hydraulic permeability via ET-1 release. Ang II may act via NO release to increase hydraulic permeability in the basal state. Finally, Ang II attenuates the increase in hydraulic permeability because of endothelial activation with platelet activating factor.