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

Abstract

1 The vasodilator properties and photochemical decomposition of two synthetic iron-sulphur-nitrosyl clusters (cluster A: [Fe4S4(NO)4], tetranitrosyl-tetra-j3-sulphido-tetrahedro-tetrairon; and B:[Fe4S3 (NO)7V-1, heptanitrosyl-tri-u3-thioxotetraferrate(-1)) have been investigated. Experiments were carried out on isolated, internally-perfused segments of rat tail artery.2 Bolus injections (10 Ml) 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 (Z=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 jM), had no effect on lightinduced vasodilator responses. However, they were (a) blocked entirely by adding oxyhaemoglobin (5 ,uM) to the internal perfusate; and (b) greatly enhanced by the enzyme superoxide dismutase (150 u ml-').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 t112 of 21 s. The amplitudes of vasodilator responses of the tail artery also decreased exponentially by increasing the time delay (t112=58 s). Superoxide dismutase (150 u ml-') 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.

Photo-Controlled Release of NO and CO with Inorganic and Organometallic Complexes

“…The iron sulfur nitrosyl cluster anions Roussin's red salt (RRS) and Roussin's black salt (RBS) [ Figure 5] were first reported over 150 years ago by Roussin, and the latter was shown to affect the vascular tone of rat tail arteries, presumably by the slow release of NO [72,73] …”

Photoactive ruthenium nitrosyls: Effects of light and potential application as NO donors

“…Early on, it was recognized that NO complexes of transition metals (metal nitrosyls) could release NO when exposed to light. For example, several iron-based nitrosyls including sodium nitroprusside (SNP, Na 2 [Fe(NO)(CN) 5 ]) [39–44] and Roussin’s salts [20,41,45–48] were found to release NO when exposed to light. However, these complexes also release NO spontaneously ( i.e.…”

Multi-photon excitation in uncaging the small molecule bioregulator nitric oxide

“…Photolysis of RBS at UV/visible wavelengths had previously been shown to release biologically relevant concentrations of NO in aerobic solutions [121,122]. Flash and continuous photolysis studies have also defined the stoichiometry (equation (5.1)) and mechanism of the photoreaction pathway in aqueous media [1,123].…”