Cellular mechanism of the positive inotropic effect of hydralazine in mammalian myocardium
| Autor: | Lin Miao, Cynthia L. Perreault, B. J. Ransil, D. G. Hurrell |
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| Rok vydání: | 1993 |
| Předmět: |
Inotrope
Male medicine.medical_specialty Stimulation Propranolol In Vitro Techniques chemistry.chemical_compound Aequorin Catecholamines Afterload Internal medicine medicine Animals Papillary muscle Pharmacology Chemistry Myocardium Ferrets Hydralazine Papillary Muscles medicine.disease Myocardial Contraction Electric Stimulation Stimulation Chemical Electrophysiology Actin Cytoskeleton medicine.anatomical_structure Endocrinology Heart failure Calcium Histamine medicine.drug Research Article |
| Zdroj: | British journal of pharmacology. 109(3) |
| ISSN: | 0007-1188 |
| Popis: | 1. The purpose of this study was to elucidate the cellular mechanism of the positive inotropic effect of hydralazine, a vasodilator widely used for afterload reduction in patients with heart failure that has also been reported to have positive inotropic effects on the heart. After isolation, right ventricular papillary muscles from the ferret were maintained in bicarbonate-buffered salt solution (30 degrees C). A concentration-response relationship was obtained for hydralazine (10(-6) to 10(-3) M). In order to mimic different levels of catecholamine release found in heart failure, we utilized two methods of stimulation: (a) threshold punctate pulses and (b) suprathreshold punctate stimulation with voltage approximately 10% above threshold. 2. In a first group of muscles (n = 16), a maximally effective concentration of hydralazine (10(-3) M) increased peak isometric tension by 39 +/- 9% (P < 0.05). Doses lower than 10(-5) M had no significant effect. The bioluminescent Ca2+ indicator, aequorin, was loaded into a subset of these muscles (n = 7). A significant increase in peak light (i.e., intracellular Ca2+) developed, concurrently with an increase in peak tension (38 +/- 5% to 66 +/- 8%). This inotropic response was associated with a decrease in time to peak tension (ms), 221 +/- 7 to 186 +/- 5 (P < 0.05), and time to peak light, 65 +/- 4 to 52 +/- 2 (P < 0.05). These effects were markedly attenuated by pretreatment with autonomic blocking agents. 3. In a second group of muscles (n = 12), histamine was used to stimulate cyclic AMP production in the presence of propranolol. Hydralazine (3 x 10-4 M) led to a shift in the pD2 (i.e. the negative log of the concentration of histamine producing 50% of the maximal response) from 6.1 +/- 0.1 to 5.9 +/- 0.1(P |
| Databáze: | OpenAIRE |
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