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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/F80    most recent 00020.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Schwartz, I. F. Articles by Schwartz, D. PubMed PubMed Citation Articles by Schwartz, I. F. Articles by Schwartz, D.

Sexual dimorphism in glomerular arginine transport affects nitric oxide generation in old male rats

Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel

Submitted 15 January 2009 ; accepted in final form 29 April 2009

Animal models suggest that decreased renal endothelial nitric oxide synthase (eNOS) activity in old males promotes renal injury, whereas females are protected. We aimed to explore whether aging alters glomerular arginine uptake by CAT-1, the selective arginine supplier to eNOS in rats. Arginine uptake by glomeruli from young males (3 mo) was significantly higher than in young females. Old males (19 mo) exhibited a significant decrease in arginine transport compared with young males, whereas no differences were observed between old and young females. CAT-1 abundance remained unchanged in all experimental groups. The abundance of PKC (CAT-1 inhibitor) was significantly augmented in young females vs. young males, old vs. young males, and in old females vs. old males. No differences in PKC content were detected between old and young females. Phosphorylated PKC was significantly increased in old rats from both genders. Tocopherol, a PKC inhibitor, produced a significant increase in arginine transport and restored NO generation in old males only. Ex vivo incubation of glomeruli from old males with PMA (PKC stimulant) significantly attenuated the effect of tocopherol on arginine uptake. In conclusion, attenuated glomerular arginine transport by CAT-1 contributes to the age-dependent, NO-deficient state in old male rats through upregulation of PKC. In old females glomerular arginine transport is protected from the effects of PKC by an unknown mechanism.

glomerular filtration rate; renal vasoconstriction