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High blood pressure in aged Fischer 344 X Brown Norway F1 rats is associated with increased oxidative stress, NFkB activation and exaggerated renal AT1R response to Ang II
Author(s) -
Chugh Gaurav,
Lokhandwala Mustafa,
Asghar Mohammad
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1016.8
Subject(s) - oxidative stress , medicine , endocrinology , blood pressure , angiotensin ii receptor type 1 , chemistry , angiotensin ii , renal function , kidney , receptor , sodium , organic chemistry
Aging is characterized by a progressive decline in physiological functions. Although the underlying mechanisms are not well understood, increasing number of evidence points towards oxidative stress as one of the primary determinants of aging. In this study, we compared 3 month‐ (adult) and 21 month‐ (aged) old Fischer 344 X Brown Norway F1 rats for age‐related changes in kidney function. We measured blood pressure, sodium potassium ATPase activity in proximal tubules, AT1 receptor binding in proximal tubular membranes, NFkB transcription factor in nuclear fractions and oxidative stress markers such as protein carbonyls and urinary 8‐isoprostane. Our results showed an increase in systolic, diastolic and mean arterial blood pressure in aged animals. In response to Ang II, there was increased stimulation of sodium potassium ATPase in aged animals accompanied by increased AT1R binding. Protein carbonyls and 8‐isoprostane were also increased in aged animals. We also found increased NFkB in nuclear fractions from aged animals. While Ang II activates NFkB through AT1 receptors, NFkB has putative response elements on AT1 receptor promoter. Therefore, it appears that age‐related increase in oxidative stress increased renal AT1R function via activating NFkB. This may have caused increased sodium retention and hypertension in aged animals (NIH/NIA AG25056, AG29904).