The characterization of cardiac histaminergic chronotropic receptors in the rabbit.

The effects of selective histamine receptor analogs were studied in spontaneously beating rabbit atria. Atrial rate was increased by histamine (an H1 and H2 agonist), 4-methylhistamine and impromidine (H2 agonists), and 2-pyridylethylamine (PEA, an H1 agonist). The responses to histamine, 4-methylhistamine, and impromidine were not affected by propranolol (1 x 10(-7) M) or reserpine pretreatment. However, the response to PEA was nearly abolished upon pretreatment with propranolol or reserpine. Cimetidine pretreatment (H2 receptor blockade) competitively antagonised the positive chronotropic effects of histamine, 4-methylhistamine, and impromidine. Promethazine pretreatment (H1 receptor blockade) competitively blocked the chronotropic effects of histamine but had no effect on the responses to 4-methylhistamine or impromidine. These results suggest that stimulation of H1 and H2 receptors will cause a positive chronotropic response.