Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension.
BACKGROUND
Prenatal environment has been shown to modify adult blood pressure profile, but the underlying mechanisms are not well understood. The role of renal immune cell infiltration, oxidative stress, and nitric oxide bioavailability in the pathogenesis was investigated.


METHODS
Adult hypertension in rat offspring was induced by maternal low protein diet. Oxidative stress was determined by quantitative immunoblotting for nitrotyrosine, and T-cell and macrophage content by immunostaining, in offspring kidneys before and after the onset of hypertension. Nitric oxide metabolites (NOx) were measured in 24-hour urines. A group of offspring was treated with the immunosuppressive drug mycophenolate mofetil (MMF) to reduce inflammation, or with the superoxide dismutase mimetic Tempol to reduce oxidative stress, for a 3-week period before the onset of hypertension.


RESULTS
During the prehypertensive stage, at 4 weeks of age, the low protein diet pups exhibited an increase in kidney nitrotyrosine content and in number of immune cells, both of which persisted in untreated animals after hypertension was established, at 8 weeks of age. Urine NOx was increased at 4 weeks and unchanged at 8 weeks of age. Both MMF and Tempol treatment prevented the immune cell infiltration, the increase in kidney nitrotyrosine abundance, and the development of hypertension. The effect on blood pressure persisted throughout the 4- to 10-week observation period after discontinuation of the treatments.


CONCLUSIONS
Renal oxidative stress and infiltrating immune cells may play a pathogenetic role in prenatally programmed hypertension. Nitric oxide bioavailability does not appear impaired.
Stewart
Tyrus
T
The Research Institute for Children and Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, 70118, USA.
Jung
Flavia F
FF
Manning
Jennifer
J
Vehaskari
V Matti
VM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002465:Cell Movement / Q000276:immunology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D005260:Female; D006977:Hypertension, Renal / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000473:pathology*; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D013113:Spin Labels; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000975:Antioxidants; D003497:Cyclic N-Oxides; D007166:Immunosuppressive Agents; D009566:Nitrates; D009573:Nitrites; D013113:Spin Labels; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D009173:Mycophenolic Acid; C001803:tempol