Effects of aminoguanidine on pre- and post-irradiation regional cerebral blood flow, systemic blood pressure and plasma histamine levels in the primate

Abstract

Exposure to ionizing radiation causes hypotension, cerebral ischemia and release of histamine (HA). To investigate the relationship among these three responses, rhesus monkeys (Macaca mulatta) received aminoguanidine (AG) (1 mg/kg), then were given either 50 Gy whole-body irradiation or sham-irradiation. Monkeys receiving AG had lower mean arterial blood pressure (MABP) than saline-treated controls. Compared to controls, rCBF was lower in irradiated monkeys but pre-treatment with AG did not influence this effect. Among untreated, irradiated monkeys, HA levels were increased only at two minutes post-irradiation, but among AG-treated, irradiated monkeys, HA levels were higher at all times postirradiation. Radiation-induced release of HA may be associated with radiation-induced hypotension and reduced rCBF, but failure of AG to alter rCBF suggests that released HA may not be the sole mediator of these effects. Because elevations in plasma HA are probably due to HA derived from degranulation of mast cells, release of other bioactive substances from mast cells may also influence these cardiovascular effects. Surprisingly, in sham-irradiated monkeys, AG alone had a slight but significant hypotensive effect.