This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 23/10/1826    most recent 01.ATV.0000090672.07568.60v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hilgers, R. H.P. Articles by De Mey, J. G.R. Search for Related Content PubMed PubMed Citation Articles by Hilgers, R. H.P. Articles by De Mey, J. G.R. Related Collections Endothelium/vascular type/nitric oxide Other Vascular biology

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1826.)
© 2003 American Heart Association, Inc.

Vascular Biology

Uterine Artery Structural and Functional Changes During Pregnancy in Tissue Kallikrein–Deficient Mice

Rob H.P. Hilgers; Sonia Bergaya; Paul M.H. Schiffers; Pierre Meneton; Chantal M. Boulanger; Daniel Henrion; Bernard I. Lévy; Jo G.R. De Mey

From the Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht (CARIM), Universiteit Maastricht, and School of Life Sciences, Transnational University Limburg (R.H.P.H., P.M.H.S., J.G.R.D.M.), Maastricht, the Netherlands, and Institut National de la Santé et de la Recherche Médicale (INSERM) U541 (S.B., C.M.B., D.H., B.I.L.) and U367 (P.M.), IFR Circulation Lariboisière, Université Paris VII, Paris, France.

Correspondence to Jo G.R. De Mey, Prof Dr, Department of Pharmacology and Toxicology, CARIM, Universiteit Maastricht, 6200 MD Maastricht, PO Box 616, Netherlands. E-mail j.demey{at}farmaco.unimaas.nl

Objective— Tissue kallikrein (TK) participates in acute flow-induced dilatation (FID) of large arteries. We investigated whether TK deficiency blunts FID and alters chronic flow-related arterial structural and functional changes in resistance-sized muscular arteries.

Methods and Results— Vasomotor responses and structural parameters were determined in uterine arteries isolated from nonpregnant, 18- to 19-day pregnant, and 7-day postpartum TK^-/- and TK^+/+ littermate mice. In TK^-/- mice, values of diameter, medial cross-sectional area (CSA), myogenic tone, and dilatation in response to acetylcholine were comparable to those values in TK^+/+ mice, but FID (0 to 100 µL/min) was significantly reduced (55±4% versus 85±4% in TK^+/+ mice). In both mouse strains, pregnancy resulted in significant increases in diameter and medial CSA and in the N^w-nitro-L-arginine methyl ester–sensitive component of FID. By 7 days after pregnancy, uterine arterial diameter and CSA values no longer differed from nonpregnant values, and FID was markedly reduced in TK^-/- and TK^+/+ mice.

Conclusions— These observations (1) confirm at the level of resistance arteries the key role of TK in FID and (2) indicate that TK deficiency does not compromise arterial remodeling and changes in the contribution of NO to FID during and after pregnancy.

Key Words: tissue kallikrein • bradykinin • uterine artery • flow-related remodeling • flow-induced vasodilatation • pregnancy • postpartum period

This article has been cited by other articles:

				N. I. Gokina, O. Y. Kuzina, R. Fuller, and G. Osol Local Uteroplacental Influences are Responsible for the Induction of Uterine Artery Myogenic Tone during Rat Pregnancy Reproductive Sciences, November 1, 2009; 16(11): 1072 - 1081. [Abstract] [PDF]

				O. W. H. van der Heijden, Y. P. G. Essers, E. Wijnands, J. G. R. Mey, L. L. H. Peeters, and G. J. J. M. van Eys Postpartum Reversal of the Pregnancy-Induced Uterine Artery Remodeling in Young, Aging, and eNOS-Deficient Mice Reproductive Sciences, July 1, 2009; 16(7): 642 - 649. [Abstract] [PDF]

				O. A. Stone, C. Richer, C. Emanueli, V. van Weel, P. H.A. Quax, R. Katare, N. Kraenkel, P. Campagnolo, L. S. Barcelos, M. Siragusa, et al. Critical Role of Tissue Kallikrein in Vessel Formation and Maturation: Implications for Therapeutic Revascularization Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 657 - 664. [Abstract] [Full Text] [PDF]

				M. Gassmann, A. Manini, T. Stallmach, B. Saam, G. Kuhn, B. Grenacher, A. Y. Bogdanova, and J. Vogel Abortion in Mice with Excessive Erythrocytosis Is Due to Impaired Arteriogenesis of the Uterine Arcade Biol Reprod, June 1, 2008; 78(6): 1049 - 1057. [Abstract] [Full Text] [PDF]

				S. M. Arribas, C. J. Daly, M. C. Gonzalez, and J. C. McGrath Imaging the vascular wall using confocal microscopy J. Physiol., October 1, 2007; 584(1): 5 - 9. [Abstract] [Full Text] [PDF]

				J. Mu and S. L. Adamson Developmental changes in hemodynamics of uterine artery, utero- and umbilicoplacental, and vitelline circulations in mouse throughout gestation Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1421 - H1428. [Abstract] [Full Text] [PDF]

				O. W.H. van der Heijden, Y. P.G. Essers, M. E.A. Spaanderman, J. G.R. De Mey, G. J.J.M. van Eys, and L. L.H. Peeters Uterine Artery Remodeling in Pseudopregnancy Is Comparable to That in Early Pregnancy Biol Reprod, December 1, 2005; 73(6): 1289 - 1293. [Abstract] [Full Text] [PDF]

				O. W.H. van der Heijden, Y. P.G. Essers, G. Fazzi, L. L.H. Peeters, J. G.R. De Mey, and G. J.J.M. van Eys Uterine Artery Remodeling and Reproductive Performance Are Impaired in Endothelial Nitric Oxide Synthase-Deficient Mice Biol Reprod, May 1, 2005; 72(5): 1161 - 1168. [Abstract] [Full Text] [PDF]

				J. G. R. De Mey, P. M. Schiffers, R. H. P. Hilgers, and M. M. W. Sanders Toward functional genomics of flow-induced outward remodeling of resistance arteries Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1022 - H1027. [Abstract] [Full Text] [PDF]

				O. W. H. van der Heijden, Y. P. G. Essers, L. H. J. Simkens, Q. G. A. Teunissen, L. L. H. Peeters, J. G. R. De Mey, and G. J. J. M. van Eys Aging Blunts Remodeling of the Uterine Artery During Murine Pregnancy Reproductive Sciences, July 1, 2004; 11(5): 304 - 310. [Abstract] [PDF]

				R. H.P. Hilgers, P. M.H. Schiffers, W. M. Aartsen, G. E. Fazzi, J. F.M. Smits, and J. G.R. De Mey Tissue Angiotensin-Converting Enzyme in Imposed and Physiological Flow-Related Arterial Remodeling in Mice Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 892 - 897. [Abstract] [Full Text]