Perinatal micronutrient supplements ameliorate hypertension and proteinuria in adult fawn-hooded hypertensive rats.
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.
Koeners
Maarten P
MP
Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands.
Braam
Branko
B
van der Giezen
Dionne M
DM
Goldschmeding
Roel
R
Joles
Jaap A
JA
D000818:Animals; D001120:Arginine / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D001794:Blood Pressure; D019587:Dietary Supplements; D005260:Female; D006973:Hypertension / Q000150:complications / Q000517:prevention & control*; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D018977:Micronutrients / Q000008:administration & dosage*; D008981:Molsidomine / Q000008:administration & dosage; D017942:Nitric Acid / Q000378:metabolism / Q000652:urine; D020030:Nitric Oxide Donors / Q000008:administration & dosage; D011188:Potassium / Q000378:metabolism / Q000652:urine; D011507:Proteinuria / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors; D012964:Sodium / Q000378:metabolism / Q000652:urine; D013654:Taurine / Q000008:administration & dosage; D014810:Vitamin E / Q000008:administration & dosage
D018977:Micronutrients; D020030:Nitric Oxide Donors; D014810:Vitamin E; D013654:Taurine; D017942:Nitric Acid; D001120:Arginine; D012964:Sodium; D008981:Molsidomine; D001205:Ascorbic Acid; D011188:Potassium