Development of a Red-Light-Controllable Nitric Oxide Releaser to Control Smooth Muscle Relaxation <i>in Vivo</i>

Abstract

We designed and synthesized a novel Si-rhodamine derivative, NORD-1, as a red-light-controllable nitric oxide (NO) releaser, on the basis of photoredox parameter analysis. Red-light-responsive NO release from NORD-1 was confirmed by ESR spin trapping and quantified with an NO electrode and by means of Griess assay. The NO release cross section (ε_{656 nm}·Φ_NO) of NORD-1 was calculated to be 3.65 × 10², which is larger than that of a previously reported yellowish-green-light-controllable NO releaser, NO-Rosa5. The photoresponsiveness of NO release from NORD-1 was precise and efficient enough to induce vasodilation <i>ex vivo</i> under Magnus test conditions. Finally, we showed that intracavernous pressure (ICP) could be controlled in rats <i>in vivo</i> with the combination of NORD-1 and a red-light source without increasing systemic blood pressure, which is a serious side effect of usual NO releasers, such as nitroglycerin and isopentyl nitrite. NORD-1 is expected to be a useful chemical tool for NO research, as well as a candidate agent to control the circulatory system.