Hilgers Rob H P, Bergaya Sonia, Schiffers Paul M H, Meneton Pierre, Boulanger Chantal M, Henrion Daniel, Lévy Bernard I, De Mey Jo G R
Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, Universiteit Maastricht, Netherlands.
Arterioscler Thromb Vasc Biol. 2003 Oct 1;23(10):1826-32. doi: 10.1161/01.ATV.0000090672.07568.60. Epub 2003 Aug 21.
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.
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 microL/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.
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.
