Pregnancy-induced modulation of calcium mobilization and down-regulation of Rho-kinase expression contribute to attenuated vasopressin-induced contraction of the rat aorta

Jan 13, 2006Vascular pharmacology

Pregnancy reduces blood vessel tightening by lowering calcium response and Rho-kinase levels in rat aortas triggered by vasopressin

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Abstract

AVP (10(-10) -3 x 10(-7) M) induced concentration-dependent contraction in aortic ring segments from nonpregnant and pregnant rats, but the maximum response was significantly reduced in pregnant rats.

Pregnancy is associated with decreased vascular reactivity to vasopressin in the rat aorta.
No significant change in the potency of vasopressin was observed between nonpregnant and pregnant rats.
Inhibition of vasopressin-induced contraction by nifedipine was significant in nonpregnant but not in pregnant rats, suggesting reduced Ca(2+)-influx through L-type Ca(2+)-channels during pregnancy.
Expression levels of Rho-associated kinase (ROCK) isoforms were significantly reduced in the aorta of pregnant rats.
Pregnancy may lead to decreased sensitization of contractile proteins to calcium, contributing to the attenuated vascular response.

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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+).

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Pregnancy-induced modulation of calcium mobilization and down-regulation of Rho-kinase expression contribute to attenuated vasopressin-induced contraction of the rat aorta

Abstract

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