title: Angiotensin II type 1 receptor activation increases microvascular hydraulic permeability.
abstract: BACKGROUND
  In addition to its vasoconstricting effects, angiotensin II (Ang II) has also demonstrated the ability to modulate microvessel permeability. We hypothesized that activation of the angiotensin II type 1 receptor (AT1) would increase hydraulic permeability.
  
  
  METHODS
  Hydraulic permeability (L(p)) was measured in rat mesenteric venules using the Landis micro-occlusion technique. Paired measures of L(p) were obtained at baseline and after perfusion with the AT1 agonist, [Sar(1)]-angiotensin II, at 10 micromol/L (n=6) and 100 micromol/L (n=6). Activation of the AT1 receptor was also achieved by perfusion with 20 nmol/L Ang II plus the angiotensin II type 2 receptor (AT2) antagonist, PD123319. In these studies, 30 micromol/L (n=6) and 300 micromol/L (n=6) of PD123319 were used.
  
  
  RESULTS
  [Sar(1)]-angiotensin II increased L(p) 2-fold with the 10 micromol/L dose (P=.04) and 4-fold with the 100 micromol/L dose (P < .001). The L(p) peak due to [Sar(1)]-angiotensin II occurred sooner than the peak observed with Ang II. PD123319 (30 micromol/L) plus 20 nmol/L Ang II increased L(p) 5-fold (P=.003), while PD123319 (300 micromol/L) plus 20 nmol/L Ang II increased L(p) 20-fold (P < .0001). The magnitude of the effect due to PD123319 (300 micromol/L) plus Ang II (20 nmol/L) was approximately twice the summation of effects due to PD123319 (300 micromol/L) alone and Ang II (20 nmol/L) alone.
  
  
  CONCLUSIONS
  We conclude that endothelial cell Ang II receptors play an important role in modulating transendothelial fluid flux. Activating the AT1 receptor increases L(p); the AT2 receptor may operate to oppose this action. Pharmacologic manipulation of Ang II receptors may be beneficial during shock states to limit intravascular fluid loss.
authors.affiliation: Department of Surgery, University of California at San Francisco-East Bay, Alameda County Medical Center, Oakland, CA 94602, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Newton
authors.forename: Brian
authors.initials: B
authors.lastname: Curran
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Victorino
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000502:physiology; D013152:Splanchnic Circulation; D014699:Venules / Q000502:physiology*
chemical_list: D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; C074793:angiotensin II, Sar(1)-