Direct measurement of periarterial nitric oxide (NO) in resistance vessels of aged WKY rats reveals elevated basal and suppressed flow‐mediated production which is normalized by apocynin.

Abstract

Abnormal regulation of the nitric oxide (NO) system may be responsible for the age‐related impairment in tissue perfusion and collateral growth. Direct, real time, in vivo measurements of NO in aging resistance vessels are not available. This study tested the hypothesis that aging is correlated with reduced basal and flow‐mediated NO production, which can be reversed by anti‐oxidant therapy. Our mesenteric model was used in young (Y) and retired breeder (RB) WKY and RB pre‐treated with apocynin (RB+Apo). NO‐ specific electrodes measured mesenteric periarterial NO simultaneously with arterial flow. After NO baseline measurement, collateral flow was varied from 50–200% of control by placement of microvascular clamps on adjacent arteries. RB had significantly increased baseline NO compared with Y (2053 ± 504 vs. 1059 ± 160 nM, p< 0.05). Periarterial NO levels were altered in proportion to blood flow changes in Y but not in RB rats (Figure 1). In RB+Apo, NO baseline was reduced (760 ± 102 nM) and flow‐mediated NO production restored in RB+Apo (Figure 1). Immunoblotting showed that RB had significantly increased phospho‐eNOS levels compared to either Y or RB+Apo. This suggests that the elevated baseline and suppressed flow‐mediated NO production may result from near maximal activation of eNOS in the RB. eNOS stimulation by reactive oxygen species produced by NADPH oxidase is a mechanism to be explored.Support: HL42898 and HL20605