Up‐regulation of Adrenal Leptin Receptor Expression and Tyrosine Hydroxylase Activation in Age‐related Hypertension

Abstract

Blood pressure (BP) and sympathetic activation have been shown to increase with age. The aim of the present study was to examine whether increased adrenal OB‐Rb expression and tyrosine hydroxylase (TH) activation mediated age‐related hypertension.Method4‐6 mth (young) and 20‐24 mth (old) male F344/BN rats (n=4‐6 rats/age) were implanted with telemetry for 24‐hrs arterial pressure (MAP) monitoring and were housed in individual metabolic cages. Adrenal leptin receptors (OB‐Ra & OB‐Rb) and TH protein expressions were determined by Western Blot.ResultsOld rats exhibited a significant increase in MAP (107±1 vs 98±1mmHg), body weight (556±11 vs 332±5g) and serum leptin (24±5 vs 5.1±0.7ng/ml) compared with young rats (p<0.05). The increased MAP was positively correlated with serum leptin (r2=0.7, p<0.0001). Western Blot analysis revealed a higher OB‐Rb expression (54%) than OB‐Ra in young adrenal. Although OB‐Ra expression did not change with age, OB‐Rb protein expression was markedly up‐regulated by 211±13% in old compared with young rats. TH activation (as measured by phosphorylated TH/total TH) in adrenal was also elevated by 185±10% in old compared with young rats.ConclusionResults of the present study suggest that the increased BP with age may, at least in part, be mediated by the elevated circulating leptin levels, up‐regulated adrenal OB‐Rb protein expression and TH activation.