+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Effect of isosorbide dinitrate and its metabolites on rabbit atrial myocardial force-frequency relationships in vitro

Effect of isosorbide dinitrate and its metabolites on rabbit atrial myocardial force-frequency relationships in vitro

Archives Internationales de Physiologie et de Biochimie 90(5): 361-364

Isosorbide dinitrate (ISDN) and its two mononitrate metabolites were studied for their effects on the force-frequency relationship of isolated rabbit left atrial preparations. ISDN (4.9 and 15 microgram/ml) (50-150 times maximum therapeutic plasma concentrations) produced no significant effect on the frequency-dependent changes in contractile force. A concentration of 90 micrograms/ml (approximately 900 times therapeutic concentrations) produced a depression of contractility normally observed at frequencies of 80-400 beats/min. The two mononitrate metabolites of ISDN (endo- and exo-nitratoisosorbide) (90 micrograms/ml and 450 micrograms/ml) failed to alter the normal-force-frequency relationship over the range of 10-400 beats/min. These concentrations are several thousand times greater than plasma levels achieved in man with therapeutic dosing of ISDN. The basic lack of effect of ISDN and its metabolites on this fundamental property of myocardial contractility under the test conditions suggests that their therapeutic action is not mediated through direct effects on myocardial excitation-contraction coupling mechanisms.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 042915408

Download citation: RISBibTeXText

PMID: 6190455

DOI: 10.3109/13813458209110371

Related references

Plasma levels of isosorbide dinitrate and its metabolites during intravenous infusion in surgical patients--effect of preoperative administration of isosorbide dinitrate. Masui. Japanese Journal of Anesthesiology 42(2): 225-232, 1993

Effect of 5-isosorbide mononitrate on isosorbide dinitrate-induced relaxation of rabbit aortic rings. Canadian Journal of Physiology and Pharmacology 62(9): 1194-1197, 1984

Comparison of the effect of isosorbide-5-mononitrate and isosorbide dinitrate in a slow-release form on exercise-induced myocardial ischemia. Journal of Clinical Pharmacology 31(7): 636-640, 1991

A comparison of the hemodynamic effect of isosorbide 5 mononitrate and isosorbide dinitrate administered in intravenous injection to patients with acute myocardial infarction. Cor et Vasa 31(5): 376-386, 1989

Patterns of isosorbide dinitrate and glyceryl trinitrate metabolites formed by selected segments of the rabbit gastrointestinal tract. Canadian Journal of Physiology & Pharmacology 66(2): 166-170, 1988

Plasma levels of isosorbide dinitrate and the isosorbide mononitrates after increasing doses of a retard preparation of isosorbide dinitrate. La Nouvelle Presse Medicale 9(34 Suppl): 2424-2427, 1980

Determination of drugs in biological fluids for the assessment of pharmacokinetics bioavailability in human studies first communication. analysis of isosorbide dinitrate and its metabolites isosorbide 2 mononitrate and isosorbide 5 mononitrate by capillary glc. PZ (Pharmazeutische Zeitung) Wissenschaft 134(3): 163-168, 1989

Comparative pharmacokinetics and bioavailability of isosorbide dinitrate and its metabolites isosorbide 5- and 2-mononitrate from delayed-release preparations. Arzneimittel-Forschung 32(9): 1138-1140, 1982

In vitro evidence of an endothelial cell-dependent antiplatelet activity for isosorbide dinitrate, but not for its 2- and 5-mononitrate metabolites. Journal of Pharmacology and Experimental Therapeutics 240(1): 234-240, 1987

Pharmacokinetics of isosorbide dinitrate sustained released isosorbide dinitrate and isosorbide 5 mononitrate. Cohn, Jd R. Rittinghausen (ed.). International Boehringer Mannheim Symposia: Mononitrates; Montreux, Switzerland, June 14-16, . Xi 320p. Springer-Verlag: Berlin, West Germany; New York, N.y., Usa. Illus. Paper. 53-66, 1985

Comparing the clinical and hemodynamic effects of nitroglycerin isosorbide dinitrate and isosorbide 5 mononitrate in acute myocardial infarction. Kardiologiya 31(10): 13-15, 1991

Comparison of the clinical and hemodynamic effects of nitroglycerin, isosorbide dinitrate and isosorbide-5-mononitrate in acute myocardial infarction. Kardiologiia 31(10): 13-15, 1991

Effect of isosorbide dinitrate infusion on the canine left ventricular force-length relationship. Japanese Heart Journal 34(1): 91, 1993

Comparison of the time to onset of action on myocardial ischaemia following intravenous administration of isosorbide dinitrate and 5-isosorbide mononitrate in Chinese patients. Arzneimittel-Forschung 54(5): 275-279, 2004