Responses of fetal ovine systemic and umbilical arteries to angiotensin II

Angiotensin II (ANG LI) contracts umbilical arteries and has been hypothesi zed to regulate fetal blood pressure primarily by altering umbilical vascul ar resistance. To determine whether systemic arteries in term fetal sheep a re sensitive to ANG II, isometric contraction of endothelium-intact isolate d fetal renal, mesenteric, and umbilical arteries in response to ANG II was studied. ANG II(10(-7) M) elicited contractile responses in all three vess els (43 +/- 8%, 99 +/- 21%, and 105 +/- 5% of the maximal response seen wit h 90 mM KCI for renal, mesenteric, and umbilical arteries, respectively). T he time course of the contractile responses differed among the vessels: ren al and mesenteric arteries exhibited rapid transient contraction followed b y relaxation, whereas umbilical artery displayed a more slowly developing b ut sustained contraction (1 +/- 0%, 3 +/- 3%,and 93 +/- 4% of maximal contr actile response at 5 min, for renal, mesenteric, and umbilical arteries, re spectively). The AT, receptor antagonist, losartan (10(-6) M), abolished co ntractile responses in renal and mesenteric arteries but only slowed the co ntraction in umbilical artery in response to ANG II and had no effect on ma ximal tension. AT, receptor blockade (PD 123319, 10(-7) M) had no significa nt effect on the response to ANG II in any vessel. Indomethacin (10(-6) M) significantly potentiated contraction to ANG II in renal and mesenteric but not umbilical arteries. Northern and Western blot analyses demonstrated th e presence of AT(1) mRNA and protein in all three vessels. Immunostaining f or the AT(1) receptor was present in endothelium and the tunics media. Thes e findings demonstrate the AT(1) receptor is present and functionally activ e in fetal systemic arteries and are consistent with previous findings that the umbilical circulation displays a greater responsiveness to ANG II than the systemic vasculature.