Pregnancy-induced hypertensive disorders (PIH) are leading causes of maternal mortality. Although the mechanism responsible for initiating and maintaining the disorder is unproven, physiologic molecular attachments in kidney and placenta play a role. The SKHF/Mcc-facp (SHHF) rat has features of the disorder, including abnormal placenta gene expression. To gain a molecular understanding of the gene expression profile associated with PIH, kidneys and placentas of SHHF rats at gestation day 20 were compared to WKY controls using microarray technology. We report that SHHF rats have spontaneous PIH, elevated total placenta weights, and reduced total pup weights than WKY controls and that they also have greater total number of mRNA transcripts expressed in placenta. Kidneys of SHHF rats, on the other hand, not only expressed disproportionately more predicted gene products with attachment sites such as RGD motifs, N-glycosylation sites, and N-myristoylation sites they also responded more profoundly to oral administration of L-arginine. We conclude that the increased abundance of transcripts whose products engage in posttranslational attachments using RGD motifs, N-glycosylation sites, and N-myristoylation sites and the reversal of these increases by oral administration of L-arginine suggests that NO may be of importance in PIH at the level of molecular attachments.
Bibliographical noteFunding Information:
We gratefully acknowledge the technical assistance of Heather Martin, Tracy Keeney, Denise Sanabria, and Joan Orellana and partial funding from the National Science Foundation (DBI 9904557). Valuable discussions were provided by the THOHT Programme team: Angella O’Mealley, Hyacinth Sankey, Molly Clunis, Marie Walford-Palmer, Karen Jackson-Reynolds, Beatrice Horton, Carlene Lewin, and Francis Williams. Initial discussions with Carol Sibblies are gratefully acknowledged. Drs. James Dobson, Jack Leonard, and Richard Pratt contributed to the microchip determination and Dr. Olive Yuan and Craig Lange contributed to the microarray determination.
- RGD motif