Importance of nicotinamide dose on blood pressure changes in mice and humans.

Abstract

The importance of nicotinamide dose on inducing blood pressure changes in mice and humans was investigated. Blood pressure measurements in human volunteers were made using an inflated cuff procedure after oral ingestion of 3 or 6 g nicotinamide. Animal blood pressure measurements were performed in fully awake nonanesthetized female CDF1 mice, 24 h after cannulation of the carotid artery. In humans, the average (+/- 1 SE) resting systolic and diastolic pressures were 122.8 mmHg (+/- 2.5) and 80.6 mmHg (+/- 2.1), respectively. They were unchanged during the first 3 h after ingestion of either 3 g or 6 g nicotinamide. The resting value (+/- 1 SE) in mice was 115.1 mmHg (+/- 4.0) and this was significantly reduced following intraperitoneal injection of 400-1000 mg/kg nicotinamide. This decrease was maximal within 15-30 min after injection and was linearly dependent on drug dose. At doses of 200 mg/kg or less, no significant effect on blood pressure was observed. Doses between 100-200 mg/kg in mice are known to be equivalent to 6 g in man and can also produce maximal radiosensitization in murine tumors. Our results, therefore, not only show that the mouse and human data are entirely consistent, but also suggest that nicotinamide-induced decreases in blood pressure are not necessary for radiosensitization.