Prenatal Sildenafil Therapy Improves Cardiovascular Function in Fetal Growth Restricted Offspring of Dahl Salt-Sensitive Rats
| Autor: | Nina D. Paauw, Jennifer M. Sasser, Michael R. Garrett, Fieke Terstappen, Sinéad M. Clarke, Bhavisha A. Bakrania, A. Titia Lely, Jaap A. Joles, Frank T. Spradley |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
medicine.medical_specialty
Mean arterial pressure Sildenafil Offspring Vasodilator Agents fetal growth retardation Renal function sildenafil citrate 030204 cardiovascular system & hematology Cardiovascular System Article Sildenafil Citrate Fetal Development 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pregnancy Internal medicine Journal Article Internal Medicine medicine Animals Mesenteric arteries Fetal Growth Retardation Rats Inbred Dahl 030219 obstetrics & reproductive medicine business.industry birth weight blood pressure Prenatal Care Rats Disease Models Animal fetal programming Endocrinology medicine.anatomical_structure Blood pressure chemistry cardiovascular system Pregnancy Animal Gestation Female Sodium nitroprusside business medicine.drug |
| Zdroj: | Hypertension Hypertension (Dallas, Tex. : 1979), 73(5), 1120. Lippincott Williams and Wilkins |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.118.12454 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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