TY - JOUR
T1 - Sexual dimorphism in glomerular arginine transport affects nitric oxide generation in old male rats
AU - Schwartz, Idit F.
AU - Chernichovski, Tamara
AU - Krishtol, Natalia
AU - Grupper, Avishai
AU - Laron, Ido
AU - Schwartz, Doron
PY - 2009/7
Y1 - 2009/7
N2 - 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 PKCα (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 PKCα content were detected between old and young females. Phosphorylated PKCα was significantly increased in old rats from both genders. αTocopherol, 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 PKCα. In old females glomerular arginine transport is protected from the effects of PKCα by an unknown mechanism.
AB - 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 PKCα (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 PKCα content were detected between old and young females. Phosphorylated PKCα was significantly increased in old rats from both genders. αTocopherol, 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 PKCα. In old females glomerular arginine transport is protected from the effects of PKCα by an unknown mechanism.
KW - Glomerular filtration rate
KW - Renal vasoconstriction
UR - http://www.scopus.com/inward/record.url?scp=67650689335&partnerID=8YFLogxK
U2 - 10.1152/ajprenal.00020.2009
DO - 10.1152/ajprenal.00020.2009
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C2 - 19420114
AN - SCOPUS:67650689335
VL - 297
SP - F80-F84
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
SN - 1931-857X
IS - 1
ER -