Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension

Autor: Flavia F. Jung, Tyrus Stewart, V. Matti Vehaskari, Jennifer Manning
Rok vydání: 2005
Předmět:
Zdroj: Kidney International. 68:2180-2188
ISSN: 0085-2538
DOI: 10.1111/j.1523-1755.2005.00674.x
Popis: Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension. Background. Prenatal environment has been shown to mod- ify adult blood pressure profile, but the underlying mechanisms are not well understood. The role of renal immune cell infil- tration, 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 kid- neys 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 my- cophenolate 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 nitroty- rosine content and in number of immune cells, both of which persisted in untreated animals after hypertension was estab- lished, at 8 weeks of age. Urine NOx was increased at 4 weeks and unchanged at 8 weeks of age. Both MMF and Tempol treat- ment prevented the immune cell infiltration, the increase in kidney nitrotyrosine abundance, and the development of hy- pertension. The effect on blood pressure persisted throughout the 4- to 10-week observation period after discontinuation of the treatments. Conclusion. Renal oxidative stress and infiltrating immune cells may play a pathogenetic role in prenatally programmed hypertension. Nitric oxide bioavailability does not appear impaired.
Databáze: OpenAIRE