Angiotensin II and [Sar1, Ile5, Ala8]angiotensin II effect on contractile activity and prostaglandin production of in vitro pregnant rat uteri.

The effect of angiotensin II and [Sar1,Ile5,Ala8]-angiotensin II on uterine contractions and the relationship of uterine prostaglandins to these effects were studied. Uterine segments from pregnant rats were monitored in vitro for isometric contractile activity in Krebs-Ringer medium (95% O2-5% CO2; 37 C). The medium was sampled periodically and assayed for prostaglandin E2, prostaglandin F2 alpha, and 13,14-dihydro-15-keto-prostaglandin F2 alpha by RIA. Angiotensin II increased frequency of contractions and integrated contractile force in a dose-related fashion. Angiotensin II (1 microgram) resulted in increased prostaglandin (PG) production, but there was no clear dose-related effect. Indomethacin significantly reduced PG production (P < 0.001); however, the contractile response to angiotensin II was not affected. [Sar1,Ile5,Ala8]Angiotensin II had no effect on spontaneous contractile activity or PG production in uteri from 18 or 21 days of pregnancy, nor did [Sar1,Ile5,Ala8]angiotensin II affect oxytocin-stimulated uterine contractions. [Sar1,Ile5,Ala8]Angiotensin II (2.5 microgram) did inhibit (P < 0.05) uterine contractions induced by angiotensin II (0.5 microgram), but PG production was not affected. In conclusion, the studies described provide evidence that angiotensin II-induced uterine contractions of in vitro pregnant rat uteri are not dependent upon increased PG production.