Angiotensin II type 2 receptor effect on microvascular hydraulic permeability

Background. Angiotensin II (Ang II) is a potent vasoconstrictor that modulates microvascular permeability. Angiotensin II type 1 (AT1) and type 2 (AT2) receptors have been described with subsequent development of their respective antagonists. We hypothesized that the AT2 receptor modulates microvascular permeability. Materials and methods. Hydraulic permeability (L-p) was measured in rat mesenteric venules using the Landis micro-occlusion technique. Following baseline L-p measurements, paired measures of microvessel. L-p were obtained after perfusion with a test solution. The test solutions consisted of the AT2 receptor agonist CGP42112A at 10 mum (n = 6), 100 mum (n = 6), and 200 mum (n = 6), as well as the AT2 receptor antagonist PD123319 at 3 mum (n = 6), 30 mum (n = 6), 300 mum (n = 6), and 600 mum (n = 6). Results. From mean baseline L-p of 0.99 +/- 0.03, 100 mum CGP42112A decreased L-p to 0.76 +/- 0.02 (P = 0.005), and 200 mum CGP42112A decreased L-p to 0.61 +/- 0.02 (P < 0.001). From mean baseline L-p of 0.90 +/- 0.05, PD-123319 increased L-p at 30 mum to 1.60 +/- 0.2 (P = 0.003), at 300 mum to 2.28 +/- 0.3 (P = 0.008), and at 600 mum to 4.30 +/- 0.9 (P = 0.03). Units for L-p are mean +/- SEM x 10(-7) cm s(-1) cmH(2)O(-1). Conclusion. AT2 activation decreased L-p, while AT2 blockade increased L-p. These changes in L-p may be explained by (1) a permeability-decreasing effect of the AT2 receptor that is induced by AT2 activation and inhibited by AT2 blockade; and/or (2) a permeability-increasing effect of the AT1 receptor observed during AT2 blockade and selective AT1 activation by endogenous locally released Ang II. These mechanisms would support the theories that the AT1. receptor increases microvascular permeability, while the AT2 receptor decreases microvascular permeability. (C) 2004 Elsevier Inc. All rights reserved.