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Positive inotropic effects of low concentrations of leukotrienes C4 and D4 in rat heart.
Am J Physiol. 1990 Oct; 259(4 Pt 2):H1239-46.AJ

Abstract

We examined the effects of leukotrienes (LT) B4, C4, D4, and E4 (0.010-2.5 ng/ml) on contractile and coronary function in isolated rat hearts. Concentration-dependent effects were examined either by the cumulative addition of LTs or by addition of specific concentrations to individual preparations. Neither LTB4 nor LTE4 produced myocardial or coronary effects at any concentration, irrespective of addition protocol. At 0.010 ng/ml, both LTC4 and LTD4 produced an increase in force that was associated with a 30% elevation in coronary pressure. Further cumulative addition of either leukotriene resulted in a negative inotropic effect and a further increase in coronary pressure. In contrast, following single additions of LTC4 or LTD4 (0.01-0.50 ng/ml) a positive inotropic effect and an increased coronary pressure were observed. LTC4 or LTD4 at 0.5 ng/ml produced a negative inotropic effect in hearts pretreated with 0.01 ng/ml of LTD4 or LTC4, respectively. Reversal of this addition protocol resulted in a negative inotropic effect of either 0.01 ng/ml LTD4 or LTC4. Verapamil and nifedipine significantly attenuated the positive inotropic and coronary constricting effect of 0.5 ng/ml LTC4 and LTD4. The addition of either LT following BAY K 8644 resulted in a negative inotropic effect, in contrast to the positive inotropic influence seen with leukotriene alone. Our results demonstrate a positive inotropic effect of low concentrations of LTC4 and LTD4 concomitant with coronary artery constriction, a phenomenon determined by leukotriene addition protocols and suggestive of LTC4/LTD4 receptor interaction. The effects of calcium channel antagonists and BAY K 8644 on the inotropic response suggest a leukotriene-mediated activation of the calcium channel resulting in increased intracellular calcium concentrations.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, University of Western Ontario, London, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1699437

Citation

Karmazyn, M, and M P. Moffat. "Positive Inotropic Effects of Low Concentrations of Leukotrienes C4 and D4 in Rat Heart." The American Journal of Physiology, vol. 259, no. 4 Pt 2, 1990, pp. H1239-46.
Karmazyn M, Moffat MP. Positive inotropic effects of low concentrations of leukotrienes C4 and D4 in rat heart. Am J Physiol. 1990;259(4 Pt 2):H1239-46.
Karmazyn, M., & Moffat, M. P. (1990). Positive inotropic effects of low concentrations of leukotrienes C4 and D4 in rat heart. The American Journal of Physiology, 259(4 Pt 2), H1239-46.
Karmazyn M, Moffat MP. Positive Inotropic Effects of Low Concentrations of Leukotrienes C4 and D4 in Rat Heart. Am J Physiol. 1990;259(4 Pt 2):H1239-46. PubMed PMID: 1699437.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Positive inotropic effects of low concentrations of leukotrienes C4 and D4 in rat heart. AU - Karmazyn,M, AU - Moffat,M P, PY - 1990/10/1/pubmed PY - 1990/10/1/medline PY - 1990/10/1/entrez SP - H1239 EP - 46 JF - The American journal of physiology JO - Am J Physiol VL - 259 IS - 4 Pt 2 N2 - We examined the effects of leukotrienes (LT) B4, C4, D4, and E4 (0.010-2.5 ng/ml) on contractile and coronary function in isolated rat hearts. Concentration-dependent effects were examined either by the cumulative addition of LTs or by addition of specific concentrations to individual preparations. Neither LTB4 nor LTE4 produced myocardial or coronary effects at any concentration, irrespective of addition protocol. At 0.010 ng/ml, both LTC4 and LTD4 produced an increase in force that was associated with a 30% elevation in coronary pressure. Further cumulative addition of either leukotriene resulted in a negative inotropic effect and a further increase in coronary pressure. In contrast, following single additions of LTC4 or LTD4 (0.01-0.50 ng/ml) a positive inotropic effect and an increased coronary pressure were observed. LTC4 or LTD4 at 0.5 ng/ml produced a negative inotropic effect in hearts pretreated with 0.01 ng/ml of LTD4 or LTC4, respectively. Reversal of this addition protocol resulted in a negative inotropic effect of either 0.01 ng/ml LTD4 or LTC4. Verapamil and nifedipine significantly attenuated the positive inotropic and coronary constricting effect of 0.5 ng/ml LTC4 and LTD4. The addition of either LT following BAY K 8644 resulted in a negative inotropic effect, in contrast to the positive inotropic influence seen with leukotriene alone. Our results demonstrate a positive inotropic effect of low concentrations of LTC4 and LTD4 concomitant with coronary artery constriction, a phenomenon determined by leukotriene addition protocols and suggestive of LTC4/LTD4 receptor interaction. The effects of calcium channel antagonists and BAY K 8644 on the inotropic response suggest a leukotriene-mediated activation of the calcium channel resulting in increased intracellular calcium concentrations. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/1699437/Positive_inotropic_effects_of_low_concentrations_of_leukotrienes_C4_and_D4_in_rat_heart_ L2 - https://journals.physiology.org/doi/10.1152/ajpheart.1990.259.4.H1239?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -