ABSTRACT
Kozo Utsumi, Yoshiki Takehara, Yoko Inai, Munehisa Yabuki, and Tomoko Kanno Kurashiki Medical Center, Kurashiki, Japan
I. INTRODUCTION
Nitric oxide (NO), a short-lived gaseous radical synthesized by NO synthase (NOS), has been identified as an important regulatory molecule in neurotransmis sion, vasodilation, platelet aggregation, and in host defenses (1-3). Endogenously generated NO readily enters neighboring cells and reversibly affects the activities of various enzymes, such as protein kinase C and the calcium-dependent protease, calpain (4,5). Nitric oxide also inhibits mitochondrial functions in various cells (6-11) by interacting with cytochrome oxidase and ferrocytochrome-c (Cyt-c) to form nitrosyl ferrocytochrome complexes (12,13). NO has been shown to inhibit superoxide radical (0 2_) production by neutrophils (14,15) through the formation of a nitrosyl complex with NADPH oxidase (16-18). Furthermore, NO de energizes mitochondria (16,19), increases intracellular free calcium (20) thereby killing various cells either by an apoptotic or a nonapoptotic mechanism (21 — 26). Endothelial cells produce substantial amounts of NO, an essential mediator for regulating guanylate cyclase (GC) activity (1,27,28) and blood pressure (1,29).
