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Increased kinin levels and decreased responsiveness to kinins during aging.
- Source :
-
The journals of gerontology. Series A, Biological sciences and medical sciences [J Gerontol A Biol Sci Med Sci] 2005 Aug; Vol. 60 (8), pp. 984-90. - Publication Year :
- 2005
-
Abstract
- Kinins are vasoactive peptides released from precursors called kininogens, and serum levels of both T- and K-kininogens increase dramatically as rats age. Kinin release is tightly regulated, and here we show that serum kinin levels also increase with age, from 63 +/- 16 nmol/L in young Fisher 344 rats to 398 +/- 102 nmol/L in old animals. Both K- and T-kininogens contribute sequentially to this increase, with the increase in middle-aged animals being driven primarily by K-kininogen, whereas the further augmentation in older rats occurs by increasing T-kininogen. By measuring ERK activation, we show that aorta endothelial cells from old animals are hyporesponsive to exogenous bradykinin. However, if serum kinin levels are experimentally decreased by lipopolysaccharide treatment, then the endothelial response to bradykinin is re-established. These results indicate that serum levels of kinins increase with age, whereas the responsiveness of target cells to kinins is reduced in these same animals.
- Subjects :
- Aging blood
Animals
Aorta drug effects
Aorta metabolism
Bradykinin pharmacology
Endothelium, Vascular drug effects
Endothelium, Vascular metabolism
Enzyme Activation drug effects
Extracellular Signal-Regulated MAP Kinases metabolism
In Vitro Techniques
Kininogens metabolism
Kinins blood
Lipopolysaccharides pharmacology
Male
Rats
Rats, Inbred F344
Aging drug effects
Aging metabolism
Kinins metabolism
Kinins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1079-5006
- Volume :
- 60
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- The journals of gerontology. Series A, Biological sciences and medical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 16127100
- Full Text :
- https://doi.org/10.1093/gerona/60.8.984