Abstract
UNLABELLED: The present study investigated the influence of Bay K 8644 and nifedipine (Nif) on the force-frequency relationship and on tetanic tension and force of contraction of failing human myocardium (PAP, n = 12). In addition, ryanodine (Rya) was studied on the force-frequency relationship. Bay K 8644 (0.1 microM) increased, but Nif (0.01 microM) reduced isometric force of contraction significantly. However, both, Bay K 8644 (2 Hz vs. 0.5 Hz:
CONTROL: -31.6 +/- 7.8%; +Bay K 8644: +103 +/- 30% (% basal); p < 0.005) as well as Nif (2 Hz vs. 0.5 Hz:
CONTROL: -8.8 +/- 9.7%; +Nif: +90.9 +/- 31.5% (% basal); p < 0.05), were able to restore a positive FFR in PAP. By measurement of tetanic tension and posttetanic potentiation in the presence of the 1,4-dihydropyridines, we support the hypothesis of the existence and functional relevance of a dihydropyridin-ryanodine receptor junctional complex. In skinned fiber preparations, Bay K 8644 showed no effect on Ca(2+)-sensitivity or caffeine induced Ca(2+)-release. Rya (10 microM) decreased force of contraction in PAP and was effective in restoring a positive FFR (2 Hz vs. 0.5 Hz:
CONTROL: -7.3 +/- 5.1%; +Rya: +98.0 +/- 31.9% (% basal); p < 0.05). Thus, the altered FFR and Ca(2+)-homeostasis in failing human myocardium may result from changes in sarcolemmal Ca(2+)-influx and/or from altered SR-Ca(2+)-load.
| Original language | English |
|---|---|
| Journal | Basic research in cardiology |
| Volume | 94 |
| Issue number | 3 |
| Pages (from-to) | 159-70 |
| Number of pages | 12 |
| ISSN | 0300-8428 |
| Publication status | Published - 01.06.1999 |
Research areas and keywords
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
- Adult
- Aged
- Calcium
- Calcium Channel Agonists
- Calcium Channel Blockers
- Calcium Channels
- Heart Ventricles
- Humans
- Ion Transport
- Middle Aged
- Myocardial Contraction
- Nifedipine
- Sarcoplasmic Reticulum
- Ventricular Function