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Importance of nicotinamide dose on blood pressure changes in mice and humans
M R Horsman1, K L Christensen, J Overgaard
1Danish Cancer Society, Department of Experimental Clinical Oncology, Aarhus.
Purpose:
The importance of nicotinamide dose on inducing blood pressure changes in mice and humans was investigated.
Methods And Materials:
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.
Results:
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.
Conclusion:
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.