Age-related hypertension and salt sensitivity are associated with unique cortico-medullary distribution of D1R, AT1R, and NADPH-oxidase in FBN rats

Abstract

We examined effects of normal (NS) and high salt (HS) on blood pressure (BP) and cortico-medullary distribution of dopamine D1 receptor (D1R), angiotensin AT1 receptor (AT1R), NADPH oxidase-gp91phox, and sodium transporters (NHE-3, Na, K ATPase) in adult and aged rats. Aged rats fed with NS diet had higher BP, which further increased with HS. HS increased D1R mRNA and protein levels in cortex and medulla of adult rats. NS or HS fed-aged rats had higher AT1R and gp91phox mRNA levels in cortex and medulla. Aged rats fed with NS diet had higher gp91phox protein levels in cortex. HS diet increased AT1R and gp91phox protein levels in medulla of aged rats. Aged rats fed with NS or HS diet had higher NHE-3 protein levels in medulla. HS increased Na, K ATPase protein levels in medulla of aged rats. HS increased urinary kidney injury molecule-1 (KIM-1) but not protein or albumin levels in aged rats. These results suggest that cortical gp91phox and medullary NHE-3 contribute to age-related hypertension. Whereas D1R (cortical and medullary) together with medullary AT1R, gp91phox and Na, K-ATPase contribute to salt sensitivity in aged rats. And, KIM-1 may be a better marker for kidney damage.