Nitric oxide: Biphasic dose responses

The capacity of nitric oxide (NO) to affect biphasic dose responses in pharmacological and toxicological systems was assessed. Numerous examples of such biphasic responses were documented, including osteoclast differentiation, various vascular responses, neutrophil migration, superoxide anion formation, exploratory behavior in rodents, vitamin D-3 levels in macrophages, human sperm motility and mobility, myocardial contraction, and other functions. The quantitative features of the dose response indicated a maximum stimulatory response usually less than twofold greater than the controls. While the stimulatory range was variable, ranging from similar to2.5 to 500-fold, the majority was less than or equal to 10-fold. These findings indicate that biphasic dose-response relationships are common manifestations of the NO-induced effects.