Effects of infused histamine: analysis of the effects of H-1 and H-2 histamine receptor antagonists on cardiovascular and pulmonary responses

Abstract

The dose-related effects of histamine on selected cardiovascular and pulmonary responses in 10 normal control and six mild allergic asthmatic subjects were investigated. Histamine was infused in sequentially increasing concentrations of 0.05, 0.1, 0.25, 0.5, and 1.0 μ/kg/min. The infusions were repeated after pretreatment with the H- I receptor antagonist hydroxyzine and/or the H-2 receptor antagonist cimetidine. All subjects manifested dose-related increases in pulse rate, pulse pressure, skin temperature, cutaneous flush, and headache; only one subject (an asthmatic) developed a significant reduction in peak expiratory flow rate. The decrease in peak expiratory flora rate in this subject was markedly attenuated by hydroxyzine pretreatment. The asthmatic subjects required somewhat larger concentrations of histamine (p < 0.10) to elicit the flush and headache than those required by normal control subjects. Although neither H-1 nor H-2 receptor antagonists alone influenced the concentration of histamine required to elicit cutaneous flushing and headaches, the combination of antagonists significantly (p < 0.0001) raised the threshold concentration of histamine required. The increase in pulse rate was significantly abrogated by hydroxyzine pretreatment; treatment with hydroxyzine plus cimetidine was no more effective than that with hydroxyzine alone. Histamine-induced increases in pulse pressure were predominantly determined by a reduction in diastolic pressure. Both the drop in diastolic pressure and increases in pulse pressure were signifcandy inhibited by pretreatment with the combination of antihistamines. Histamine-induced increases in skin temperature were not influenced by prior antihistamine therapy. Therefore histamine-induced alterations in blood pressure, cutaneous vascular dilation (flushing), and headache reflect stimulation of both H-1 and H-2 receptors and require antagonism of both for attenuation. Histamine-induced airway obstruction and tachycardia may be H-1 responses antagonized by hydroxyzine. Skin temperature responses are less clear. Prevention of histamine-induced cardiopulrnonary responses by pretreatment with H-1 and H-2 antihistamines may be an effective prophylaxis in circumstances in which histamine release is likely.