The angiotensin II receptor type 2 agonist CGP 42112A stimulates NO production in the porcine jejunal mucosa

BACKGROUND This study was conducted to elucidate if nitric oxide is released by the porcine jejunal mucosa upon selective stimulation of AT2 receptors and the possible involvement of iNOS, and to investigate the presence of jejunal AT1 and AT2 receptors. Young landrace pigs were anaesthetized with ketamine and alpha-chloralose. Jejunal luminal NO output was assessed by intraluminal tonometry and analysed by chemiluminescense. Western blot analysis quantified mucosal iNOS and detected AT1 and AT2 receptor protein expression. AT1 and AT2 receptor RNA expression was detected by rtPCR. RESULTS Baseline luminal NO output correlated significantly to baseline mucosal iNOS-protein content. In animals treated with the AT2-receptor agonist CGP42112A (n = 11) luminal NO output increased significantly (at 0.1 micrograms kg(-1) min(-1) and 1.0 micrograms kg(-1) min(-1)), but not in animals simultaneously treated with the AT2-receptor antagonist PD123319 (bolus 0.3 mgkg-1, infusion 0.03 mg kg(-1) h(-1)) (n = 7). No differences in iNOS protein expression were found between groups or before/after the administration of drugs. Western blot and rtPCR recognised expression of the AT1 and AT2 receptors in jejunal tissue. CONCLUSION The results suggest that activation of AT2 receptors increases jejunal luminal NO output. This response was not due to an increase in the expression of the iNOS protein in the mucosa.