Adulthood
hypertension can be programmed by
preeclampsia.
Preeclampsia is associated with an imbalance in vasoactive factors, including
nitric oxide (NO),
hydrogen sulfide (H2S), and renin-angiotensin system (RAS). We examined whether maternal
N-acetylcysteine (NAC)
therapy prevented maternal
suramin treatment-induced programmed
hypertension in offspring and explored the effects of this
therapy on NO, H2S, and RAS pathways in the kidneys. Pregnant Sprague-Dawley rats were intraperitoneally administered 60 mg/kg
suramin alone on Gestational Days 10 and 11 and were treated with or without 1% NAC through
drinking water during the entire pregnancy and lactation period. Male offspring were divided into four groups (n = 8-10/group): control,
suramin, NAC, and
suramin plus NAC. All rat offspring were euthanized at 12 wk of age. Maternal
suramin treatment induced programmed
hypertension in male offspring, which was prevented by maternal NAC
therapy.
Suramin-induced programmed
hypertension was associated with increased plasma
asymmetric dimethylarginine (ADMA, an
NO synthase inhibitor) level, decreased plasma
l-arginine-to-ADMA ratio, and decreased renal
dimethylarginine dimethylaminohydrolase (an ADMA-metabolizing
enzyme) activity. Protective effects of NAC against
suramin-induced programmed
hypertension were associated with an increase in plasma
glutathione level, increase in renal
3-mercaptopyruvate sulfurtransferase level, and restoration of
suramin-induced reduction in H2S synthesis in the kidneys.
Suramin treatment exerted negligible effect on the RAS pathway in the adult male offspring kidneys. Our data suggested interplay among
suramin, ADMA-NO pathway, and H2S synthesis pathway in programmed
hypertension. Furthermore, NAC administration in pregnant rats with
hypertension prevented programmed
hypertension in adult offspring.