Soluble guanylate cyclase stimulation in late gestation does not mitigate asymmetric IUGR or cardiovascular risk induced by placental ischemia in the rat

This study tested the hypothesis that stimulation of sGC until birth attenuates asymmetric IUGR mitigating increased cardiovascular risk in offspring. Sham or RUPP surgery was performed at gestational day 14 (G14); vehicle or sGC stimulator, Riociguat (10mg/kg/day, s.c.) were administered G14 until birth. Birth weight was reduced in offspring from RUPP (intrauterine growth restricted or IUGR), sGC RUPP (sGC IUGR), and sGC Sham (sGC Control) compared to Sham (Control). Crown circumference was maintained but abdominal circumference was reduced in IUGR and sGC IUGR compared to Control indicative of asymmetrical growth. Gestational length was prolonged in sGC RUPP, and survival at birth was reduced in sGC IUGR. Probability of survival to postnatal day 2 was also significantly reduced in IUGR and sGC IUGR versus Control, and in sGC IUGR versus IUGR. At 4 months of age blood pressure was increased in male IUGR and sGC IUGR, but not male sGC Control born with symmetrical IUGR. Global longitudinal strain was increased and stroke volume was decreased in male IUGR and sGC IUGR compared to Control. Thus, late gestational stimulation of sGC does not mitigate asymmetric IUGR or increased cardiovascular risk in male sGC IUGR. Furthermore, late gestational stimulation of sGC is associated with symmetrical growth restriction in sGC Control implicating contraindications in normal pregnancy.PMID:33739156 | DOI:10.1152/ajpheart.00033.2021
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Source Type: research