Enhanced [Ca ]i in renal arterial smooth muscle cells of pregnant rats with reduced uterine perfusion pressure

Murphy, Jason G., Jason N. Herrington, Joey P. Granger, and Raouf A. Khalil. Enhanced [Ca2 ]i in renal arterial smooth muscle cells of pregnant rats with reduced uterine perfusion pressure. Am J Physiol Heart Circ Physiol 284: H393–H403, 2003. First published September 12, 2002; 10.1152/ajpheart.00247.2002.—Reduction of uterine perfusion pressure (RUPP) during late pregnancy has been suggested to trigger increases in renal vascular resistance and lead to hypertension of pregnancy. We investigated whether the increased renal vascular resistance associated with RUPP in late pregnancy reflects increases in intracellular Ca2 concentration ([Ca2 ]i) and contraction of renal arterial smooth muscle. Single smooth muscle cells were isolated from renal interlobular arteries of normal pregnant Sprague-Dawley rats and a rat model of RUPP during late pregnancy. The cells were loaded with fura 2 and both cell length and [Ca2 ]i were measured. In cells of normal pregnant rats incubated in Hanks’ solution (1 mM Ca2 ), ANG II (10 7 M) caused an initial increase in [Ca2 ]i to 414 13 nM, a maintained increase to 149 8 nM, and 21 1% cell contraction. In RUPP rats, the initial ANG II-induced [Ca2 ]i (431 18 nM) was not different from pregnant rats, but both the maintained [Ca2 ]i (225 9 nM) and cell contraction (48 2%) were increased. Membrane depolarization by 51 mM KCl and the Ca2 channel agonist BAY K 8644 (10 6 M), which stimulate Ca2 entry from the extracellular space, caused maintained increases in [Ca2 ]i and cell contraction that were greater in RUPP rats than control pregnant rats. In Ca2 -free (2 mM EGTA) Hanks’ solution, the ANG IIand caffeine (10 mM)-induced [Ca2 ]i transient and cell contraction were not different between normal pregnant and RUPP rats, suggesting no difference in Ca2 release from the intracellular stores. The enhanced maintained ANG II-, KCland BAY K 8644-induced [Ca2 ]i and cell contraction in RUPP rats compared with normal pregnant rats suggest enhanced Ca2 entry mechanisms of smooth muscle contraction in resistance renal arteries and may explain the increased renal vascular resistance associated with hypertension of pregnancy.