Pregnancy-induced modulation of calcium mobilization and down-regulation of Rho-kinase expression contribute to attenuated vasopressin-induced contraction of the rat aorta.
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+).
Katoue
Maram G
MG
Department of Pharmacology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
Khan
Islam
I
Oriowo
Mabayoje A
MA
D000577:Amides / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D047908:Intracellular Signaling Peptides and Proteins; D009543:Nifedipine / Q000494:pharmacology; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D054460:rho-Associated Kinases
D000577:Amides; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D011725:Pyridines; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009543:Nifedipine; D002118:Calcium