on August 21, 2003
Published online before print August 21, 2003, doi: 10.1161/01.ATV.0000090672.07568.60
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Submitted on July 18, 2003
Accepted on July 31, 2003
Uterine Artery Structural and Functional Changes During Pregnancy in Tissue Kallikrein-Deficient Mice
Rob H.P. Hilgers ;
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.
* To whom correspondence should be addressed. 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 Nw-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
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