Vasodilator responses of rat isolated tail artery enhanced by oxygen‐dependent, photochemical release of nitric oxide from iron‐sulphur‐nitrosyls

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Abstract
1 The vasodilator properties and photochemical decomposition of two synthetic iron-sulphur-nitrosyl clusters (cluster A: [Fe4S4(NO)4], tetranitrosyl-tetra-μ3-sulphido-tetrahedro-tetrairon; and B[Fe4S3 (NO)7]−1, heptanitrosyl-tri-μ3-thioxotetraferrate(−1)) have been investigated. Experiments were carried out on isolated, internally-perfused segments of rat tail artery. 2 Bolus injections (10 μl) of A or B (>0.25 mM) delivered into the internal perfusate generated sustained (or S-type) vasodilator responses, characterized by a persistent plateau of reduced tone due to NO released from clusters which enter and become trapped within endothelial cells. Clusters were therefore irradiated with visible laser light (λ = 457.9 or 514.5 nm) either (a) in solution, while passing through a glass tube en route to the artery; or (b) when retained within the endothelium, by illuminating the artery directly during the plateau of an S-type response. Irradiation produced an additional vasodilator response, the magnitude of which depended upon wavelength and laser beam energy. 3 The nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (100 μm), had no effect on light-induced vasodilator responses. However, they were (a) blocked entirely by adding oxyhaemoglobin (5 μm) to the internal perfusate; and (b) greatly enhanced by the enzyme superoxide dismutase (150 u ml−1). 4 Photolysis of cluster B was measured by absorption spectroscopy and by detecting NO released with an electrochemical sensor. The photochemical reaction was found to be oxygen-dependent. The half-time for inactivation of cluster-derived NO was measured by interposing different lengths of tubing (i.e time delays) between the photolysis tube and NO sensor. The steady-state probe current decayed exponentially with increasing delay time, with a t½ of 21 s. The amplitudes of vasodilator responses of the tail artery also decreased exponentially by increasing the time delay (t½ = 58 s). Superoxide dismutase (150 u ml−1) prevented this from happening, showing that ‘inactivation’ of cluster-derived NO was caused by reaction with superoxide anions formed during photolysis. 5 We conclude that potentiation of vasodilator responses to iron-sulphur-nitrosyl clusters by visible light is due to an oxygen-dependent photochemical reaction which accelerates the release of ligated nitrosyl groups as free NO. Based on our measurements, we estimate that ca 100 pM NO is sufficient to produce a just-detectable additional vasodilatation and that the ED50 dose is ca 3.7 nM.

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