Cardiac contractile and metabolic effects mediated via the myocardial H2-receptor adenylate cyclase system
- 1 February 1981
- journal article
- research article
- Published by Springer Nature in Zeitschrift für Die Gesamte Experimentelle Medizin
- Vol. 179 (1) , 81-98
- https://doi.org/10.1007/bf01852128
Abstract
Summary The present study characterizes myocardial effects of two new histaminergic H2-receptor specific compounds, impromidine, and dimaprit, on cardiac contractile and metabolic parameters of the guinea pig heart and human papillary muscle in comparison to the well-known effects of catecholamines. Impromidine and dimaprit produced a dose-dependent stimulation of the right and left ventricular contractile force in the isolated perfused biventricular catheterized guinea pig heart with maximal stimulation rates equal to those of isoproterenol. Hemodynamic equieffective doses of isoproterenol (2.8 × 10−9 mol/l), histamine (1.1 × 10−5 mol/l), impromidine (4.6 × 10−7 mol/l), and dimaprit (8.5 × 10−6 mol/l) induced nearly identical increases in tissue concentrations of c-AMP. All compounds dose-dependently enhanced the activity of the myocardial adenylate cyclase with very similar KA-values in a particulate sarcolemmal membrane preparation of both guinea pig ventricles and human papillary muscles. No effect of either compound was seen on cardiac phosphodiesterase activity. Selective administration of theβ 1-blocking agent metoprolol and the H2-receptor antagonist cimetidine clearly discriminates two independent receptors linked to the sarcolemmal adenylate cyclase system in the guinea pig and human myocardium. This is further supported by results obtained fromβ-receptor-binding studies in which an interference of impromidine and dimaprit with the stereospecific binding of (−)[3H]-dihydroalprenolol to cardiacβ-receptors could be definitely excluded. The possible therapeutic role of both H2-agonists on the non-ischemic, surviving myocardium, which is transiently refractory toβ-adrenergic stimulation by catecholamines after myocardial infarction, will be discussed.Keywords
This publication has 24 references indexed in Scilit:
- Impaired beta-adrenergic stimulation in the uninvolved ventricle post-acute myocardial infarction: Reversible defect due to excessive circulating catecholamine-induced decline in number and affinity of beta-receptorsAmerican Heart Journal, 1981
- Effects of histamine on human isolated heart muscle: comparison with effects of noradrenalineJournal of Pharmacy and Pharmacology, 1980
- A new highly potent and short-acting analgesic, carfentanyl (R 33799), in combination with the hypnotic agent, etomidat (r 26490), as a method of anaesthesia in guinea pigsZeitschrift für Die Gesamte Experimentelle Medizin, 1980
- Cardiovascular studies with impromidine (SK&F 92676), a new very potent and specific histamine H2-receptor agonistJournal of Pharmacy and Pharmacology, 1979
- Behandlung des akuten Myokardinfarktes mit MetoprololDeutsche Medizinische Wochenschrift (1946), 1978
- Plasma norepinephrine in congestive heart failurePublished by Elsevier ,1978
- Effects of dobutamine in patients with acute myocardial infarctionThe American Journal of Cardiology, 1977
- Activation of myocardial adenyl cyclase by histamine in guinea pig, cat, and human heartJournal of Clinical Investigation, 1971
- Changes in norepinephrine stores in the canine heart following experimental myocardial infarctionAmerican Heart Journal, 1971
- URINARY EXCRETION OF FREE NORADRENALINE AND ADRENALINE FOLLOWING ACUTE MYOCARDIAL INFARCTIONThe Lancet, 1967