Wimalawansa Sunil J
Robert Wood Johnson Medical School, Department of Medicine, New Brunswick, NJ 08903, USA.
Expert Opin Pharmacother. 2008 Aug;9(11):1935-54. doi: 10.1517/14656566.9.11.1935.
Nitric oxide (NO) deficiency is implicated in many pathophysiological processes in mammals. NO is a ubiquitous molecule involved in multiple cellular functions. Uncontrolled or inappropriate production of NO may lead to several disease states including septic shock, rheumatoid and inflammatory arthropathies, and expansion of cerebral damage after stroke. However, to date, there are no therapeutic agents available that can overcome these conditions. Similarly, underproduction of NO by NO synthase or enhanced breakdown of NO also leads to diseases such as hypertension, ischemic conditions, pre-eclampsia, premature delivery, among others. NO donor therapies are indicated in these conditions.
Nitroglycerin and nitrates (NO donors) have been used as therapeutic agents for the past century, particularly to treat vascular disease, and the only significant adverse effects are headaches. NO donors are highly cost-effective and have beneficial effects in multiple body systems. When the body cannot generate NO via NO synthase or due to rapid turnover leading to inadequate amounts of NO available for biological homeostasis, administration of exogenous NO, or prolongation of the actions of endogenous NO, are practical ways to supplement NO.
Recipients of such therapy include patients with angina pectoris, coronary artery disease, hypertension, osteoporosis, gastrointestinal motility disorders, pregnancy-related disorders including premature delivery, pre-eclampsia, vulvodynia, and erectile dysfunction in men. Postmenopausal NO deficiency is rectified with hormone replacement therapy, which enhances local production of NO. Declining local NO production secondary to estrogen deficiency in postmenopausal women and perhaps in older men could be one of the reasons for age-related increased incidences of cardiovascular events and sexual dysfunction. Thus, in addition to supplementation of NO compounds in acute situations like alleviating angina and erectile dysfunction, chronic NO therapy is cost-effective in decreasing cardiovascular events, and improving the urogenital system and skeletal health.
一氧化氮（NO）缺乏与哺乳动物的许多病理生理过程有关。NO是一种普遍存在的分子，参与多种细胞功能。NO的不受控制或不适当产生可能导致多种疾病状态，包括感染性休克、类风湿性和炎性关节病，以及中风后脑损伤的扩大。然而，迄今为止，尚无能够克服这些状况的治疗药物。同样，NO合酶产生NO不足或NO分解增强也会导致诸如高血压、缺血性疾病、先兆子痫、早产等疾病。在这些情况下需要使用NO供体疗法。
在过去的一个世纪里，硝酸甘油和硝酸盐（NO供体）一直被用作治疗药物，特别是用于治疗血管疾病，唯一显著的副作用是头痛。NO供体具有很高的成本效益，并且在多个身体系统中具有有益作用。当身体无法通过NO合酶产生NO，或由于快速周转导致用于生物稳态的NO量不足时，给予外源性NO或延长内源性NO的作用是补充NO的实用方法。
接受这种治疗的患者包括心绞痛、冠状动脉疾病、高血压、骨质疏松症、胃肠动力障碍患者，与妊娠相关的疾病，包括早产、先兆子痫、外阴痛，以及男性勃起功能障碍患者。绝经后NO缺乏可通过激素替代疗法纠正，该疗法可增强局部NO的产生。绝经后女性以及可能老年男性中由于雌激素缺乏导致局部NO产生减少，可能是心血管事件和性功能障碍随年龄增加发生率上升的原因之一。因此，除了在缓解心绞痛和勃起功能障碍等急性情况下补充NO化合物外，慢性NO治疗在降低心血管事件、改善泌尿生殖系统和骨骼健康方面具有成本效益。
