The vasoactive effect of angiotensin (Ang)-(1-7) in mesenteric resistance arteries together with its plasma and kidney concentration and urinary excretion was assessed in pregnant and virgin rats. Mesenteric arteries (230-290 microm) were mounted in a pressurized myograph system and Ang-(1-7) concentration-dependent response curves (10(-10)-10(-5) M) were determined in arteries preconstricted with endothelin-1 (10(-7) M). The Ang-(1-7) response was investigated in vessels with and without pretreatment with the Ang-(1-7) antagonist [D-[Ala(7)]-Ang-(1-7)] (10(-7) M). Ang-(1-7) caused a significantly enhanced, concentration-dependent dilation of mesenteric vessels (EC(50) = 2.7 nM) from pregnant compared with virgin female rats. D-[Ala(7)]-Ang-(1-7) eliminated the vasodilator effect of Ang-(1-7). There was no significant change in plasma concentration of Ang-(1-7) in pregnant animals. On the other hand, 24 h urinary excretion and kidney concentration of Ang-(1-7) were significantly higher in pregnant animals. The increased mesenteric dilation to Ang-(1-7) with enhanced kidney concentration and 24 h urinary excretion rate of Ang-(1-7) suggests an important role for this peptide in cardiovascular regulation during pregnancy.