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The inhibitory action of protamine on human internal thoracic artery contractions: the effect of free hemoglobin.
- Source :
-
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery [Eur J Cardiothorac Surg] 2003 Jun; Vol. 23 (6), pp. 962-8. - Publication Year :
- 2003
-
Abstract
- Objective: We investigated the mechanism of the protamine action and the effects of free hemoglobin on protamine-induced responses in endothelium-denuded and-intact human internal thoracic artery (ITA) rings precontracted with phenylephrine (PE) or high KCl.<br />Methods: Samples of redundant ITA obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected to a computer-based data acquisition system.<br />Results: Acetylcholine (Ach, 10(-8)-10(-5) M) caused a concentration-dependent relaxation of PE-precontracted ITA rings. Free hemoglobin (0.1 and 0.5 microM) produced a concentration-dependent and significant decrease in sensitivity (pD(2)) and maximal contractility (E(max)) in response to Ach in PE-precontracted ITA rings (P<0.0001). Protamine (50-800 microg/ml), free hemoglobin (0.1 and 0.5 microM), nitric oxide (NO) blocker N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM) or soluble guanylate cyclase inhibitor methylene blue (10 microM) administration did not cause a significant alteration on basal tonus of endothelium-intact or -denuded ITA rings. Protamine (50-800 microg/ml) induced concentration-dependent relaxation responses in ITA rings precontracted by either PE or high KCl. There was no difference in sensitivity or maximal response to protamine between the endothelium-intact and -denuded rings. Incubation of endothelium-intact or -denuded ITA rings with L-NAME or free hemoglobin or methylene blue did not cause a significant inhibition on relaxation responses to protamine. ITA ring contractions induced by stepwise addition of calcium to high KCl solution with no calcium were almost completely inhibited by protamine (P<0.0001).<br />Conclusions: It was suggested that protamine induced relaxation responses in human ITA rings is not NO- or endothelium-dependent but seems to depend on the interactions of protamine with calcium influxes and/or calcium release from intracellular stores in this tissue.
- Subjects :
- Calcium pharmacology
Dose-Response Relationship, Drug
Endothelium, Vascular drug effects
Endothelium, Vascular physiology
Guanylate Cyclase antagonists & inhibitors
Humans
Methylene Blue pharmacology
Muscle Contraction physiology
Muscle, Smooth, Vascular drug effects
Muscle, Smooth, Vascular physiology
NG-Nitroarginine Methyl Ester pharmacology
Nitric Oxide Synthase antagonists & inhibitors
Phenylephrine pharmacology
Potassium Chloride pharmacology
Thoracic Arteries physiology
Vasoconstrictor Agents pharmacology
Hemoglobins metabolism
Muscle Contraction drug effects
Protamines pharmacology
Thoracic Arteries drug effects
Vasodilator Agents pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1010-7940
- Volume :
- 23
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 12829073
- Full Text :
- https://doi.org/10.1016/s1010-7940(03)00141-6