Abstract 481: Age-related Hypertension and Salt-sensitivity Are Associated With Specific Kidney Cortico-medullary Distribtion of D1R, AT1R And NADPH-oxidase

Abstract

We recently reported that oxidative stress has a causal role in increasing kidney angiotensin II AT1 receptor (AT1R) and decreasing dopamine D1 receptor (D1R) functions in the aging Fischer Brown Norway (FBN) rats. These renal receptors by counter-regulating each other’s functions maintain sodium homeostasis and normal blood pressure (BP). Here, we examined systolic BP and kidney distribution (cortex vs medulla) of these receptors as well as of an oxidant producing enzyme (gp 91phox -NADPH-oxidase) in response to 4-week normal-salt (NS, 0.4% NaCl) and high-salt (HS, 8% NaCl) feeding in adult (3-month) and old (21-month) FBNs. BP in conscious animals was measured by radio-telemetry. Distribution of D1R, AT1R and gp 91phox were determined by RT-PCR and western blotting. We found that NS-fed old rats had higher BP (adult vs old: 105±1 vs 118 ±1 mmHg), which further increased with HS feeding in these rats (adult vs old: 111±1 vs 124 ±1 mmHg). The levels of D1R mRNA in cortex or in medulla were not different between NS-fed adult and old rats, but decreased in both cortex [adult vs old: 67 ± 15 vs 54±16 density unit (DU)] and medulla (adult vs old: 22±15 vs 11±3 DU) only in HS-fed old rats. Contrary to this, AT1R mRNA levels were higher only in cortex of old rats fed either NS (adult vs old: 81 ± 23 vs 102± 34 DU) or HS (adult vs old: 80 ± 17vs 98 ± 36 DU). Moreover, there were similar gp 91phox mRNA levels in the cortex and medulla of adult and old rats fed either NS or HS. But, its protein levels were higher in the cortex of old rats fed NS (adult vs old: 60±7 vs 112±8 DU) and HS (adult vs old: 61±3 vs 94±15 DU), and increased only in the medulla with HS feeding in these rats (adult vs old: 12±1 vs 28±2 DU). Our results suggest that there exists a specific cortico-medullary expression pattern of D1R, AT1R and gp 91phox with NS and HS feeding in old rats, which might be contributing to age-related hypertension and salt-sensitivity in FBNs.