Age‐related hypertension is associated with impairments in kidney dopamine D1 and angiotensin II AT1 receptor functions

Abstract

The kidney dopamine D1 (D1R) and angiotensin II AT1 (AT1R) receptors by regulating sodium transporters maintain sodium homeostasis and blood pressure (BP). We have reported that the aging process is associated with changes in kidney function and increase in BP. Therefore, we hypothesized that impairments in kidney D1R and AT1R functions contribute to altered sodium balance and high BP in aging. To test this hypothesis, we measured BP and D1R and AT1R functions in adult (3‐month) and old (21‐month) Fischer 344 X Brown Norway F1 rats (a rat aging model). The D1R and AT1R functions were determined by administering D1‐like receptor agonist (SKF‐38393) and AT1 receptor antagonist (candesartan) respectively. We found that systolic, diastolic and mean arterial blood pressures were higher in old rats. SKF‐38393 increased urinary sodium excretion (UNaV) and fractional sodium excretion (FENa) in adult but not in old rats. While candesartan increased UNaV in both adult and old rats, the magnitude of natriuretic response was greater in old rats. Candesartan‐mediated increase in FENa over basal was also higher in old rats. Although the basal UNaV was similar in both groups, basal FENa was lower in old rats. These studies demonstrate the presence of diminished D1R and exaggerated AT1R functions in the aging kidneys, which may contribute to sodium retention and increase in blood pressure in old rats (NIH/NIA AG25056, AG29904).