Dietary Nitrate as an Adjuvant Therapy for Hypertensive Pregnancies and a Nutritional Modifier of Cardiovascular Programming in Offspring

Objectives: Hypertension during pregnancy is the leading cause of pregnancy-related mortality in the United States leading to long-term cardiovascular perturbations for both offspring and mothers. Although dietary nitrate is known to decrease blood pressure (BP), it is unknown whether dietary nitrate will augment the effects of hypertension medication therapies. This study evaluated the effects of dietary nitrate alone or with labetalol on BP and echocardiograph measures of spontaneously hypertensive rat (SHR) dams and their offspring. Methods: Twenty-week-old female SHR were randomized to control (n=4), nitrate (21 mg/day) (n=4), labetalol (20 mg/kg/day) (n=4), or nitrate and labetalol (N+L) (n=4) for four weeks prior to mating with treatment continuing through gestation, lactation, and weaning. Vascular outcomes included tail-cuff plethysmography for dams and offspring and echocardiography for dams. Data for pups were collected at P25, P40, and P60 representing weanling, adolescent, and young adult phases. Results: After four weeks of supplementation, control SHR had higher systolic BP (SBP) than nitrate (p=0.021) or labetalol (p=0.023). At P40, control SHR had higher SBP and diastolic BP (DBP) compared to nitrate (p=0.038 and p=0.034, respectively) or N+L (p=0.018 and p=0.020, respectively). Further, left ventricular internal end diastolic diameter (LVIDd) was significantly different between groups (p=0.039) such that post-hoc analysis revealed control dams had higher LVIDd than N+L SHR (p=0.05), albeit post-hoc results were non-significant. At P25, pups from control SHR had higher SBP than pups from all treated dams (p< 0.05). At P40, pups from control SHR had significantly higher DBP than pups from labetalol SHR (p=0.012). There were no significant differences in BP for offspring at P60. Conclusions: Results suggest that nitrate supplementation, alone or with labetalol, can lower BP in both dams and offspring. Additional research is warranted to explore the mechanistic pathways by which nitrate treatment impacts blood pressure and heart structure and function of hypertensive dams and their offspring.