ORCID Profile
0000-0003-3608-7083
Current Organisation
UMC utrecht
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2019
DOI: 10.1161/HYPERTENSIONAHA.118.12454
Abstract: Fetal growth restriction (FGR) is associated with increased risk for cardiovascular and renal disorders in later life. Prenatal sildenafil improves birth weight in FGR animal models. Whether sildenafil treatment protects against long-term cardiovascular and renal disease in these offspring is unknown. The aim of this study is to test the hypothesis that prenatal sildenafil ameliorates cardiovascular and renal function in FGR offspring of Dahl salt-sensitive rats. Sildenafil citrate (60 mg/kg per day) or control gel diet (containing 0.3% salt) was administered from gestational day ten until birth. In male and female offspring, the mean arterial pressure was measured by telemetry in 1 subset from week 5 until week twenty. Echocardiographic parameters, glomerular filtration rate, and fractional electrolyte excretion were determined in another subset at week 9. Aortic and mesenteric artery rings were prepared to assess endothelial-dependent (acetylcholine) and -independent (sodium nitroprusside) vasorelaxation (week 10). The rise in mean arterial pressure per week was attenuated in treated versus untreated male offspring. Mesenteric arteries showed an increased endothelium-dependent relaxation and improved endothelium-independent relaxation in treated versus control male offspring. No differences in aortic relaxation, echocardiographic parameters or renal function were observed between groups. Prenatal sildenafil treatment subtly improves cardiovascular but not renal function in the offspring of this FGR rat model. Translationally, in utero treatment could be beneficial for cardiovascular programming in a sex-specific manner however, caution is warranted since recent human trials have been halted because of potentially deleterious neonatal side effects when treating pregnancies complicated with severe FGR with sildenafil.
Publisher: American Physiological Society
Date: 05-2017
DOI: 10.1152/AJPREGU.00510.2016
Abstract: Women with a history of preecl sia (PE) have an increased risk to develop cardiovascular and renal diseases later in life, but the mechanisms underlying this effect are unknown. In rats, we assessed whether placental ischemia results in long-term effects on the maternal cardiovascular and renal systems using the reduced uterine perfusion pressure (RUPP) model for PE. Sprague-Dawley rats received either a Sham or RUPP operation at gestational day 14. The rats were followed for 8 wk after delivery (Sham n = 12, RUPP n = 21) at which time mean arterial pressure (MAP conscious), 24-h albuminuria, glomerular filtration rate (GFR transcutaneous, FITC-sinistrin), and cardiac function (Vevo 770 system) were assessed. Subsequently, all rats were euthanized for mesenteric artery vasorelaxation and histology of heart and kidney. At 8 wk after delivery, there was no difference in MAP and albuminuria. However, RUPP rats showed a significantly reduced GFR [2.61 ± 0.53 vs. 3.37 ± 0.74 ml/min P = 0.01]. Ultrasound showed comparable cardiac structure, but RUPP rats had a lower left ventricular ejection fraction (62 ± 7 vs. 69 ± 10% P = 0.04). Heart and kidney histology was not different between Sham or RUPP rats. Furthermore, there were no differences in endothelial-dependent or -independent vasorelaxation. We show that exposure to placental ischemia in rats is accompanied by functional disturbances in maternal renal and cardiac function 8 wk after a preecl tic pregnancy. However, these changes were not dependent on differences in blood pressure, small artery vasorelaxation, or cardiac and renal structure at this time point postpartum.
No related grants have been discovered for Nina Paauw.