Development of a Red-Light-Controllable Nitric Oxide Releaser to Control Smooth Muscle Relaxation <i>in Vivo</i>
Naoya Ieda, Yuji Hotta, Ayaka Yamauchi, Atsushi Nishikawa, Takahiro Sasamori, Daisuke Saitoh, Mitsuyasu Kawaguchi, Kazunori Kimura, Hidehiko Nakagawa
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 (ε656 nm·ΦNO) 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 ex vivo under Magnus test conditions. Finally, we showed that intracavernous pressure (ICP) could be controlled in rats in vivo 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.