Mesenteric Vascular Responsiveness in a Rat Model of Pregnancy-Induced Hypertension

Reduced perfusion to the placenta in early pregnancy is believed to be the initiating factor in the development of preeclampsia, triggering local ischemia and systemic vascular hyperresponsiveness. This sequence of events creates a predisposition to the development of altered vascular function and hypertension. This study was designed to determine the influence of placental insufficiency on the responsiveness of mesenteric resistance arteries in an animal model of preeclampsia. Placental insufficiency was induced by reduction in uteroplacental perfusion pressure (RUPP) in experimental Sprague-Dawley rat dams. The uterine branches of the ovarian arteries and the abdominal aortae of pregnant rats were surgically constricted on gestational Day 14. Dams in the control group underwent a sham procedure. Rats were euthanized on gestational Day 20, followed by removal of the small intestine and adjacent mesentery. First-order mesenteric resistance arteries were mounted on a small vessel wire myograph and challenged with incremental concentrations of vasoconstrictors and vasorelaxants. Mesenteric arteries in dams with placental insufficiency demonstrated an increased maximal tension to phenylephrine (7.15 ± 0.15 vs. 5.4 ± 0.27 mN/mm, P <0.001); potassium chloride at 60 mM (3.43 ± 0.11 vs. 2.77 ± 0.14 mN/mm, P <0.01) and 120 mM (3.92 ± 0.18 vs. 2.97 ± 0.16 mN/mm, P <0.01); and angiotensin II (2.59 ± 0.42 vs. 1.51 ± 0.22 mN/mm, P <0.05). Maximal relaxation to endothelium-dependent relaxants acetylcholine and calcium lonophore (A23187) was not significantly reduced. Data suggest that placental insufficiency leads to hyperresponsiveness to vasoconstrictor stimuli in mesenteric arteries.