Direct measurement of nipradilol-derived nitric oxide in the vascular wall of canine femoral arteries.

Nipradilol (NP: 3,4-dihydro-8-[2-hydroxy-3-isopropylamino]propoxy-3-nitroxy-2H-1-benzopyran) shows not only beta-adrenoreceptor-blocking effects but also nitroglycerin-like vasodilatory action. We aimed to directly measure NP-derived nitric oxide (NO) in the vascular wall. An NO-sensitive microelectrode was inserted into the vascular media (the vasodilatory action site of NO) of isolated perfused canine femoral arteries. Each vessel was perfused with 15 microM NP in the presence or absence of 1 mM N-ethylmaleimide (NEM; a thiol alkylator). Intravascular-wall NO concentration increased 181+/-34 nM during NP perfusion (P<0.001 vs basal, n=10) with an average base-to-peak reaction time of 1.5+/-0.1 min (P<0.0001, n=8). Concomitant perfusion of NEM with NP attenuated the intravascular-wall NO production significantly (P<0.0001 vs NP only). It is concluded that NP is metabolized to NO in the vascular wall of an isolated canine femoral artery in large part through a metabolic process involving thiols with a base-to-peak reaction time of about 1.5 min.