BACKGROUND: In fawn-hooded hypertensive (FHH) rats, a model of hypertension, impaired preglomerular resistance, hyperfiltration, and progressive renal injury, we recently observed that supporting perinatal nitric oxide (NO) availability with the NO donor molsidomine persistently reduced blood pressure (BP) and ameliorated renal injury in male and female offspring. However, beneficial effects of perinatal molsidomine treatment were more pronounced in female than in male FHH rats. METHODS: To evaluate whether such protective effects could also be achieved with micronutrients, and whether the gender-dependent differences could be confirmed, we tested perinatal exposure to the micronutrients L-arginine, taurine, vitamin C, and vitamin E (ATCE) in FHH rats. Perinatal micronutrients increased urinary NO metabolite, sodium and potassium excretion only at 4 weeks of age, i.e., at the end of treatment. RESULTS: From 12 weeks onwards, control males had a significantly higher systolic BP (SBP) than females (P < 0.01); however after perinatal micronutrients, this difference was no longer present, indicating a pronounced antihypertensive effect of perinatal micronutrients in males (interaction P < 0.001). Development of proteinuria was attenuated by perinatal micronutrients in males and females. However, only females showed reduced glomerular filtration rate, filtration fraction, and glomerulosclerosis (GS) after perinatal micronutrients. CONCLUSIONS: In sum, perinatal micronutrients that enhance NO availability ameliorated development of hypertension and proteinuria in FHH rats. Antihypertensive effects were more pronounced in male FHH offspring, whereas renal protective effects were more pronounced in female FHH offspring. Mechanisms underlying gender-specific consequences of perinatal micronutrients require further study.
BACKGROUND: In fawn-hooded hypertensive (FHH) rats, a model of hypertension, impaired preglomerular resistance, hyperfiltration, and progressive renal injury, we recently observed that supporting perinatal nitric oxide (NO) availability with the NO donormolsidomine persistently reduced blood pressure (BP) and ameliorated renal injury in male and female offspring. However, beneficial effects of perinatal molsidomine treatment were more pronounced in female than in male FHH rats. METHODS: To evaluate whether such protective effects could also be achieved with micronutrients, and whether the gender-dependent differences could be confirmed, we tested perinatal exposure to the micronutrients L-arginine, taurine, vitamin C, and vitamin E (ATCE) in FHH rats. Perinatal micronutrients increased urinary NO metabolite, sodium and potassium excretion only at 4 weeks of age, i.e., at the end of treatment. RESULTS: From 12 weeks onwards, control males had a significantly higher systolic BP (SBP) than females (P < 0.01); however after perinatal micronutrients, this difference was no longer present, indicating a pronounced antihypertensive effect of perinatal micronutrients in males (interaction P < 0.001). Development of proteinuria was attenuated by perinatal micronutrients in males and females. However, only females showed reduced glomerular filtration rate, filtration fraction, and glomerulosclerosis (GS) after perinatal micronutrients. CONCLUSIONS: In sum, perinatal micronutrients that enhance NO availability ameliorated development of hypertension and proteinuria in FHH rats. Antihypertensive effects were more pronounced in male FHH offspring, whereas renal protective effects were more pronounced in female FHH offspring. Mechanisms underlying gender-specific consequences of perinatal micronutrients require further study.
Authors: Weibin Zhou; Edgar A Otto; Andrew Cluckey; Rannar Airik; Toby W Hurd; Moumita Chaki; Katrina Diaz; Francis P Lach; Geoffrey R Bennett; Heon Yung Gee; Amiya K Ghosh; Sivakumar Natarajan; Supawat Thongthip; Uma Veturi; Susan J Allen; Sabine Janssen; Gokul Ramaswami; Joanne Dixon; Felix Burkhalter; Martin Spoendlin; Holger Moch; Michael J Mihatsch; Jerome Verine; Richard Reade; Hany Soliman; Michel Godin; Denes Kiss; Guido Monga; Gianna Mazzucco; Kerstin Amann; Ferruh Artunc; Ronald C Newland; Thorsten Wiech; Stefan Zschiedrich; Tobias B Huber; Andreas Friedl; Gisela G Slaats; Jaap A Joles; Roel Goldschmeding; Joseph Washburn; Rachel H Giles; Shawn Levy; Agata Smogorzewska; Friedhelm Hildebrandt Journal: Nat Genet Date: 2012-07-08 Impact factor: 38.330