Influence of glyceryl trinitrate on force of contraction and action potential of guinea-pig myocardium. 1975

M Korth

1. The inotropic effect of glyceryl trinitrate (GTN) was studied in guinea-pig papillary muscles and atrial strips by analysing the isometric contraction curve and the monophasic action potential (AP). 2. GTN, 7X10(-5)M in papillary muscles and at 1.4x10(-4)M in atrial strips. The maximum of the contractile force was reached in both preparations at 2x10(-4)M GTN. Positive inotropic effects were transitory (3--5 min) and were followed by marked negative inotropic effects. 3. In the presence of GTN, only 15 of 26 papillary muscles showed a positive inotropic response and there was a great variance in its intensity. Prior exposure of papillary muscles to a low GTN concentration, which by itself reduced force of contraction (like every single GTN application), was the prereqch by itself reduced force of contraction (like every single GTN application), was the prerequisite for the positive inotropic effect of a subsequent higher GTN concentration. In atrial strips the positive inotropic action was consistent and uniform. The maximum force of contraction in response to single applications of GTN was only about 50% of that in response to cumulatively increased GTN concentrations. 4. In the presence of 5x10(-4)M GTN, the tyramine concentration-effect curve was shifted to the left (by one log unit at the ED50 level). 5. Beta-Adrenoceptor blockade by(+/-)-propranolol (5x10(-6)M) or noradrenaline depletion by pretreatment of the animals with reserpine (5 mg/kg, 18--22 hrs prior to the experiment)prevented the positive inotropic effects of GTN in both preparations. Hence, the GTN-induced increase in contractile force is induced by the liberation of noradrenaline and an inhibitory effect on the monoamine oxidase (MAO) of sympathetic nerve endings might be involved. 6. In atrial preparations exposed to 5x10(-4)M GTN, time to peak force (tu) and relaxation time(t2) were shortened by 12% and 33%, respectively. Pretreatment of the animals with reserpine prevented the shortening og t1 and changed the shortening of t2 from 33% to 19%. 7. In papillary muscles, 5x10(-4) M GTN shortened t1 by 10%, while t2 was prolonged by 17% in noradrenaline-depleted, and by 36% in control muscles. Prolongation of t2 at 5x10(-4)M GTN was accompanied by an increase in the duration of the monophasic action patential (AP) in reserpine-pretreated as well as in control muscles by 12% and 26%, respectively (measured at 90% repolarization). The same GTN concentration slowed the maximum rate of depolarisiation by 32%. After 35 min the AP returned to approximately the control value. In the presence of 5x10(-4) M GTN, noradrenalin (1x10(-5)M) lengthened the AP by 38% in both, control muscles and noradrenaline-depleted preparations.

UI MeSH Term Description Entries
D008297 Male Males
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D010210 Papillary Muscles Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae. Muscle, Papillary,Muscles, Papillary,Papillary Muscle
D011433 Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs. Dexpropranolol,AY-20694,Anaprilin,Anapriline,Avlocardyl,Betadren,Dociton,Inderal,Obsidan,Obzidan,Propanolol,Propranolol Hydrochloride,Rexigen,AY 20694,AY20694,Hydrochloride, Propranolol
D012110 Reserpine An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. Raunervil,Raupasil,Rausedil,Rausedyl,Serpasil,Serpivite,V-Serp,V Serp
D003864 Depression, Chemical The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Depression,Chemical Depressions,Depressions, Chemical
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005260 Female Females

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