Abstract
Pregnancy is associated with attenuated vascular reactivity to a variety of contractile agonists. Heme oxygenases are expressed in the placenta, and it has been suggested that the heme oxygenase/carbon monoxide (HO/CO) pathway plays a significant role in regulating blood flow through the feto-placental unit. In this study we investigated the possible involvement of heme oxygenases in the reduced vascular reactivity associated with pregnancy. Arginine vasopressin (AVP) (10−10–3×10−7 M) induced concentration-dependent contraction of aortic ring segments from non-pregnant and pregnant (16–19 days) rats. Pregnancy did not alter the sensitivity to AVP (pD2=8.5±0.1 and pD2=8.4±0.2 in non-pregnant and pregnant rats, respectively) but significantly reduced the maximum response (107.9±12.7% and 38.6±7.4%, respectively, relative to noradrenaline-induced contraction). Western blot analysis revealed the expression of HO-2 but not HO-1 isoform in both groups. There was a significant increase in the expression and activity of HO-2 protein in aortic tissues from pregnant rats compared with those from age-matched non-pregnant rats. In the presence of L-NAME to inhibit nitric oxide (NO) synthesis, tin protoporphyrin IX (SnPP-IX, 10−5 M), an inhibitor of heme oxygenase, did not significantly affect AVP-induced contraction in aorta segments from pregnant and non-pregnant rats. It was concluded that, though pregnancy increased the expression and activity of HO-2 in the aorta, HO-2 was not involved in the attenuated response to AVP.
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Acknowledgments
This study was supported in part by a grant from the College of Graduate Studies of Kuwait University to M.G.K. We are also grateful to the staff of the Animal Resource Center for their kind assistance.
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Katoue, M.G., Khan, I. & Oriowo, M.A. Increased expression and activity of heme oxygenase-2 in pregnant rat aorta is not involved in attenuated vasopressin-induced contraction. Naunyn Schmied Arch Pharmacol 372, 220–227 (2005). https://doi.org/10.1007/s00210-005-0018-1
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DOI: https://doi.org/10.1007/s00210-005-0018-1