Enhanced [Ca2+]I and Contractility of Renal Arterial Smooth Muscle in a Rat Model of Hypertension Produced by Reduction of Uterine Perfusion Pressure in Late Pregnancy
Reduction of uterine perfusion pressure during late pregnancy has been suggested to trigger increases in renal vascular resistance and pregnancy-induced hypertension; however, the cellular mechanisms involved are unclear. We investigated whether reduction of uterine perfusion pressure in late pregnancy is associated with increased [Ca2+]i and contractility of renal arterial smooth muscle. Single smooth muscle cells were isolated from renal interlobular arteries of late pregnant Sprague-Dawley rats and a hypertensive pregnant rat model produced by chronic reduction in uterine perfusion pressure (RUPP). The cells were loaded with fura-2 and cell length and [Ca2+]i were measured. In cells of pregnant rats incubated in Hank’s solution (1 mmol/L Ca2+), resting [Ca2+]i was 62±3 nmol/L and cell length was 69±3 μm. In RUPP rats, resting [Ca2+]i (101±3 nmol/L) was significantly greater and cell length (53±2 μm) was shorter than pregnant rats. In pregnant rats, angiotensin II (AII, 10-7 mol/L) caused transient increase in [Ca2+]i to 412±25 nmol/L followed by a maintained increase to 158±15 nmol/L, and 23±2% cell contraction. In RUPP rats, the AII-induced [Ca2+]i transient (434±22 nmol/L) was not significantly different from pregnant rats, but the maintained [Ca2+]i was significantly elevated to 198±7 nmol/L and cell contraction was increased to 33±3%. In pregnant rats, the Ca2+ channel agonist Bay K8644 (1 μmol/L) caused maintained increase in [Ca2+]i to 292±12 nmol/L and 31% contraction that were significantly enhanced in RUPP rats. In Ca2+-free (2 mmol/L EGTA) Hank’s, AII- and caffeine (10 mmol/L)-induced [Ca2+]i transient and cell contraction were not significantly different between pregnant and RUPP rats suggesting no difference in Ca2+ release from intracellular stores. The enhanced basal, maintained AII- and Bay K8644-induced [Ca2+]i and cell contractility in RUPP rats suggest enhanced Ca2+ entry mechanisms of smooth muscle contraction in resistance renal arteries and may, in part, explain the increased renal vascular resistance associated with pregnancy-induced hypertension.