Functional role of angiotensin II AT 2 receptor in modulation of AT 1 receptor‐mediated contraction in rat uterine artery: involvement of bradykinin and nitric oxide

The aim of the present study was to explore the mechanisms underlying angiotensin II AT 2 receptor modulation of AT 1 receptor‐mediated vasoconstriction in the rat isolated uterine artery, since previous studies have suggested that AT 2 receptors may oppose AT 1 receptor‐mediated effects. Segments of uterine artery were obtained from Sprague–Dawley rats and mounted in small vessel myographs. Concentration–response (CR) curves to angiotensin II (0.1 n M –0.1 μ M ) were constructed in the absence and presence of PD 123319 (AT 2 antagonist; 1 μ M ), HOE 140 (bradykinin B 2 antagonist; 0.1 μ M ), Nω ‐nitro‐ L ‐arginine (NOLA) (NOS inhibitor; 30 μ M ), as well as combinations of these inhibitors. Contractile responses to angiotensin II were expressed as a percent of the response to a K + depolarizing solution. PD 123319 (1 μ M ) potentiated angiotensin II‐induced contractions; reflected by a significant four‐fold leftward shift of the angiotensin II CR curve. HOE 140 (0.1 μ M ) significantly increased the pEC 50 of the angiotensin II CR curve. The combination of HOE 140 plus PD 123319 did not produce additive potentiation. NOLA (30 μ M ) significantly enhanced sensitivity to angiotensin II, seen as a five‐fold leftward shift of the curve, and an augmented maximum contractile response. Combinations of PD 123319 (1 μ M ) plus NOLA, and of HOE 140 (0.1 μ M ) plus NOLA, both induced a similar magnitude of potentiation. Cyclic GMP measurements confirmed angiotensin II‐induced activation of the nitric oxide (NO) pathway. In conclusion, AT 2 receptor‐mediated inhibition of angiotensin II‐induced contraction of the rat uterine artery involves NO production; a component of which occurs through a bradykinin B 2 receptor pathway.British Journal of Pharmacology (2003) 140 , 987–995. doi: 10.1038/sj.bjp.0705484