Normal pregnancy is characterized by attenuated vascular reactivity to a variety of contractile agonists and this, in part, has been attributed to increased circulating vasodilators and/or impaired Ca(2+)-influx through L-type Ca(2+)-channels. Our hypothesis in this study was that reduced Ca(2+)-dependent (influx) and Ca(2+)-independent (involving the RhoA/Rho-kinase pathway) mechanisms contributed to attenuated vasopressin-induced contraction of the pregnant rat aorta. AVP (10(-10) -3 x 10(-7) M) induced concentration-dependent contraction of aortic ring segments from nonpregnant and pregnant rats with no significant change in pD(2) values (8.53+/-0.11 and 8.33+/-0.18 in nonpregnant and pregnant rats, respectively). The maximum response was however significantly reduced in aorta segments from pregnant rats. Nifedipine (10(-6) M) significantly inhibited AVP-induced contraction in artery segments from nonpregnant but not pregnant rats indicating a reduced role for Ca(2+)-influx through L-type Ca(2+)-channels in AVP-induced contractions of the pregnant rat aorta. Western blot analysis revealed the expression of ROCK-1 and ROCK-II isoforms in aorta segments from both groups. There was a significant reduction in the expression of ROCK-1 and ROCK-II isoforms in aortic tissues from pregnant rats. This is consistent with the reduced potency of Y-27632 in inhibiting AVP (10(-7) M) induced contraction in aorta segments from pregnant rats. It was concluded that pregnancy-induced attenuated vascular response to AVP was due to decreased Ca(2+)-influx through L-type Ca(2+)-channels and decreased sensitization of the contractile myofilaments to Ca(2+).