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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Ramirez
René
R
Department of Surgery, UCSF-East Bay, Alameda County Medical Center, Oakland, California, USA.
Chong
Terry
T
Victorino
Gregory P
GP
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004347:Drug Interactions; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D010972:Platelet Activating Factor; D000804:Angiotensin II; C082887:PD 145065; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester