Ageing diminishes endothelium-dependent vasodilatation and tetrahydrobiopterin content in rat skeletal muscle arterioles.

摘要: Ageing reduces endothelium-dependent vasodilatation through an endothelial nitric oxide synthase (NOS) signalling pathway. The purpose of this study was to determine whether arginase activity diminishes in skeletal muscle arterioles from old rats, and NOS substrate (l-arginine) cofactor (tetrahydrobiopterin; BH4) concentrations are reduced. First-order were isolated the soleus young (6 months old) (24 male Fischer 344 rats. In vitro changes luminal diameter response stepwise increases flow determined presence inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 10−5 mol l−1), Nω-hydroxy-nor-l-arginine (NOHA, 5 × 10−4 exogenous l-arginine (3 10−3 l−1) or precursor for BH4 synthesis sepiapterin (1 μmol l−1). Arteriolar content via HPLC. decreased flow-mediated by 52%, difference abolished with inhibition. Neither inhibition nor addition had any effect on vasodilatation; arteriolar also not different between age groups. lower rats (94 ± 8 fmol (mg tissue)−1) relative controls (234 21 tissue)−1), elevated These results demonstrate that impairment induced is due altered mechanism arterioles, but result increased limited substrate. Rather, age-related deficit appears be result, part, bioavailability.