1 The eects of pertussis toxin (PT) and the role of histaminergic H 1 , H 2 and H 3 receptor blockade on the actions of histamine on blood pressure, heart rate, blood gas values, and mortality were studied in anaesthetized rats. 2 Four days after treatment with PT, histamine dose-dependently decreased mean arterial blood pressure (MAP) and PT enhanced the histamine-induced decrease in MAP. In the PT but not in the inactivated PT (IPT) or saline treated group three out of six animals died after the highest dose of histamine (300 mg kg 71 , i.v.) 3 In order to determine the type of histamine receptor that mediates HS, 4 days after PT the selective antagonists mepyramine (H 1 ), cimetidine (H 2 ) and clobenpropit (H 3 ) were administered 20 min before the challenge with histamine. Mepyramine completely inhibited both the enhanced histamine-induced decrease in MAP and mortality brought about by PT. Cimetidine and clobenpropit had no protective eects, but rather enhanced the histamine-induced mortality elicited by PT. 4 The present study shows that PT caused HS in rats which is primarily mediated via H 1 and secondarily via H 2 and H 3 receptors. These results are considered to be a ®rst step in the elucidation of the mechanism(s) of the HS test used in the quality control of acellular pertussis vaccine.
SummaryVaccination of young children with diphtheria, tetanus, poliomyelitis and pertussis (DTPoP) vaccine is effective in preventing outbreaks of whooping cough but adverse events sometimes occur. This pilot study shows that in freely-moving rats, multiple treatment with DTPoP (at day 0 and day 5, 6 ml/kg i.v.) increased heart rate (HR) for 5 days after the first treatment and decreased diastolic blood pressure (DBP) for at least 26 days after the first treatment and inhibited the circadian rhythm of HR and DBP for at least 10 days. DTPo vaccine, containing no pertussis vaccine, was free of such effects. Thus, in rats, the pertussis component of DTPoP acts on the cardiovascular system and disturbs its circadian rhythm. The contribution of these findings to clinical adverse effects is as yet unknown and needs further research.
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