I004 SPONTANEOUS SUSTAINED PREGNANCY- ASSOCIATED HYPERTENSION IN SHHF/Mcc-fa cp RATS: A POSSIBLE MODEL FOR IMPAIRED BLOOD PRESSURE REGULATION IN PREGNANT WOMEN L.C. Sharkey, S.A. McCune, and J.C.S. Fray*. Tufts University School of Vet. Med., The Ohio State University, and Univ. Mass. Med. School Hypertension is a major contributor to maternal and fetal morbidity and mortality, with the potential to result in ma- ternal death, intrauterine growth retardation, and the need for iatrogenic preterm delivery of infants. Progress in un- derstanding the pathogenesis of hypertensive disorders of pregnancy has been slowed by the scarcity of animal models that develop the disorders spontaneously and in so doing model the situation in humans. Twenty nulliparous 5-month-old female SHHF/Mcc-fa cp (SHHF) rats were matched by initial tail cuff systolic blood pressure and ran- domly assigned to either breeding or control groups. A small group of 4 females became pseudopregnant after breeding. Initial blood pressure was mildly elevated at 141 (2.5, SEM) mm Hg. Systolic blood pressures were recorded in all females every other day and the pressures of pseudo- pregnant and pregnant females were significantly greater than controls at day 6 of pregnancy, reaching a plateau by 8 –10 days of pregnancy at approximately 40 mm Hg higher than nonpregnant control rats. Blood pressure began to de- cline in pseudopregnant females at day 12 of pregnancy, but was persistently high until after delivery in pregnant fe- males. Half of the pregnant females were sacrificed at day 21 of gestation, and the remainder were allowed to deliver. Interestingly, despite the sustained hypertension, the mean heart weight of the hypertensive pregnant rats was 1.2 (0.02, SEM) g, similar to normotensive females of this age and in contrast to older. Nonpregnant females of this strain with blood pressures in this range have an average heart weight of 1.6 –1.8 g, suggesting that the expected cardiac hypertrophy did not develop in pregnant hypertensive fe- males. Placental weights from sacrificed females at day 21 of gestation (0.60  0.02, n = 34) were larger than those re- ported for spontaneously hypertensive rats (SHRs), but pup weights (2.68  0.64, n = 36) were comparable. Histologic examination of the left ventricle, liver, kidney, and placenta did not reveal pathologic lesions. Thus, SHHF rats which develop pregnancy-associated hypertension had small for gestational age pups similar to SHRs but larger placental weights. The SHHF rat may be of significance as a model of spontaneous pregnancy-associated hypertension and al- tered rates of intrauterine growth. Key Words: Preeclampsia; small birth weight; hypertension-associated pregnancy I005 SMALL FOR GESTATIONAL AGE OFFSPRINGS IN RATS MAY BE INDUCED BY FACTORS OTHER THAN PLACENTAL HYPOPERFUSION D. Sanabria, V. Sebek, M. Suarez, L. Sharkey, and J. Fray*. Univ. Mass. Med. School and Tufts Univ. School of Vet. Medicine Placental hypoperfusion has been suggested to be a princi- pal trigger of preeclampsia and its myriad consequences, including small for gestational age (SGA) offsprings. The view is that reducing placental perfusion by the end of the first trimester induces placental dysfunction which subse- quently leads to systemic hypertension and then SGA off- springs. Consequently, placental hypoperfusion in animals has been used as a model for the induction of preeclampsia, but the etiology is still unknown and urine analysis is rarely performed to determine whether ionic dysregulation may be involved. SGA is also associated with hypertension, but it is unresolved whether the SGA is caused directly by the pla- cental hypoperfusion or by the consequent hypertension and the possibility of SGA in insulin resistant rats without placental hypoperfusion remains to be explored. To test this hypothesis, SHR and WKY rats were subjected to surgical placental hypoperfusion at the end of the first trimester (day 8) and the pups removed and weighed at day 20. Sham operated rats served as controls. Birth weights of pups of WKY rats subjected to placental hypoperfusion was insig- nificantly different from that of control (3.46  0.05 g, n = 29 vs 3.24  0.06 g, n = 22), prompting the suggestion that hypoperfusion itself may not cause SGA births. Similarly, birth weights of pups of SHRs were not smaller in SHRs subjected to placental hypoperfusion (2.37  0.08 g, n = 63 vs 1.79  0.01 g, n = 24). Before pregnancy, urine analysis of SHRs showed a 2-fold increase in Na and HCO 3 excretion, but a 2-fold reduction in K excretion and a 10-fold reduction in Ca excretion compared to WKY rats. Interestingly, pH in urine of prepregnant SHRs was significantly alkaline (pH 8.34  0.28) compared to that of WKY rats (pH 6.97  1.46). During pregnancy, urine analysis of SHRs showed substan- tial increases in Na, K, Ca, and HCO 3 with a reduction of pH. Day 20 birth weights of pups from normotensive Zucker rats were 2.54  0.06 g (n = 38), values comparable to those in SHRs but lower than those of WKY rats with or without placental hypoperfusion. These results suggest that the mechanisms inducing hypertension and preeclampsia dur- ing placental hypoperfusion may be different from those causing small for gestational age offsprings and that small for gestation age may involve ionic mechanisms involved in cell signalling in addition to growth and size regulation. Rodent models may be valuable tools for elucidating these mechanisms. Key Words: Preeclampsia; small birth weight; placental hypoperfusion I006 GENDER DIFFERENCES IN THE RESPONSE OF SHR TO ACUTE AND CHRONIC SUPEROXIDE DISMUTASE MIMETIC, TEMPOL J.F. Reckelhoff, L.A. Fortepiani, H. Zhang, K. Srivastava, M.J. Smith. University of Mississippi Medical Center, Jackson, MS These studies were performed to determine if there are differences in response to TEMPOL which could account for gender differences in the development of hypertension in SHR. In the first study male (M) and female (F) SHR (n = 5– 8/grp) were anesthetized and systemic hemodynamics were measured; following a 20-min control period, TEM- AJH–APRIL 2000 –VOL. 13, NO. 4, PART 2 POSTERS: Gender Issues 277A Downloaded from https://academic.oup.com/ajh/article-abstract/13/S2/277A/187083 by guest on 30 May 2020