Spontaneous pregnancy-induced hypertension and intrauterine growth restriction in rats

The SHHF/Mcc-fa(cp) (spontaneous hypertension and heart failure) rat is adv anced as a novel and suitable non-primate model of pregnancy-associated hyp ertension and fetal growth restriction because it simultaneously has sponta neous pregnancy-associated hypertension, small for gestational age (SGA) of fsprings, and altered placental gene expression. Pregnancy-associated hyper tension is a major contributor to maternal and fetal morbidity and mortalit y with the potential to result in maternal death and the need for iatrogeni c preterm. delivery. It has been reported to develop spontaneously in human s, but not in animals; consequently, progress in identifying the cause and pathogenesis of this disorder has been hampered. Spontaneous hypertension a nd heart failure rats develop hypertension spontaneously as they age, there fore we sought to determine whether these rats developed hypertension and S GA offsprings during pregnancy. Our results show that systolic blood pressu re (BP) increased >40 mm Hg by the end of the first trimester and remained at this elevated level for the remainder of pregnancy, but decreased after parturition. Placenta weights of SHHF rats (0.60 +/- 0.02 g, n = 36) were s ignificantly higher than Wistar-Kyoto (WKY) rats (0.42 +/- 0.01 g, n = 22, P < .05), but pup weights were significantly lower (2.68 <plus/minus> 0.06 g for SHHF rats compared to 3.24 +/- 0.06 g for WKY controls, P < .05). His tologic examination revealed pathologic lesions in neither heart, liver, pl acenta, nor kidney. L-Arginine administered in drinking water prevented the elevation of BP, particularly during the third trimester. Placentas from S HHF rats displayed altered expression of several genes whose protein produc ts have been implicated in preeclampsia, including serotonin receptor, sodi um channel, carbonic anhydrase, estrogen receptor regulator, major histocom patibility complex proteins, superoxide dismutase, and angiotensiogen. In a ddition, gene expression profiling showed alteration of a number of subcell ular putative myristoylproteins not previously associated with preeclampsia , particularly those engaged in post-translational modifications in the pla centa. Thus, SHHF rats may be a valuable tool, because it simultaneously ha s spontaneous pregnancy-associated hypertension, SGA offsprings, and altere d placental gene expression. Am J Hypertens 2001;14:1058-1066 (C) 2001 Amer ican Journal of Hypertension, Ltd.