Use of impromidine to define specific histamine H-2 effects on gastric secretion, heart rate and blood pressure in conscious dogs.

Histamine H-2 receptor-mediated effects of the very selective H-2 agonist (H-1:H-2 < 1:1000) impromidine on gastric acid, chloride and pepsin secretion and on heart rate (HR) and systolic blood pressure were compared to those of histamine in five conscious gastric fistula dogs. In each dog, impromidine in a step-dose response (0.46 to 46 nmol/kg.hr) in 45-min steps was given without and with a background infusion of cimetidine (2 mumol/kg.hr). Histamine acid phosphate was given in a seven step-dose response (18 to 1350 nmol/kg. hr). Impromidine produced the same maximum stimulation of gastric HCI output, increase of HR and fall in systolic blood pressure as histamine. Impromidine was some 38 times more potent than histamine in stimulation of acid (ED50 3.8 vs. 145 nmol/kg.hr) and 30 times more potent in raising HR (ED50 5.6 vs. 172 nmol/kg.hr). Cimetidine competitively inhibited the effects of impromidine with similar pA2 values for each effect (acid, 5.99; chloride, 6.03; change in HR, 6.03; and change in systolic blood pressure, 6.32). The effects of impromidine on pepsin secretion were qualitatively and quantitatively similar to those of histamine and other H-2 agonists with weak stimulation at low doses and progressive inhibition with increasing doses of impromidine. Coupling the results with the known high specificity of impromidine, gastric acid secretion, chronotropism and hypotension all seem to be purely H-2-mediated effects of histamine in the intact conscious dog.