The inhibitory action of protamine on human internal thoracic artery contractions: the effect of free hemoglobin

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Golbasi I., NACİTARHAN C., ÖZDEM S., Turkay C., Karakaya H., ŞADAN G., ...Daha Fazla

EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, cilt.23, sa.6, ss.962-968, 2003 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 23 Sayı: 6
  • Basım Tarihi: 2003
  • Doi Numarası: 10.1016/s1010-7940(03)00141-6
  • Dergi Adı: EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.962-968
  • Anahtar Kelimeler: protamine, human internal thoracic artery, hemoglobin, nitric oxide, ENDOTHELIUM-DEPENDENT RELAXATION, VASCULAR SMOOTH-MUSCLE, RABBIT MESENTERIC-ARTERY, NITRIC-OXIDE, RELAXING FACTOR, AORTA, SYNTHASE, SULFATE, CALCIUM, CELLS
  • Akdeniz Üniversitesi Adresli: Evet

Özet

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. 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. 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 muM) 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 mug/ml), free hemoglobin (0.1 and 0.5 muM), nitric oxide (NO) blocker N-omega-nitro-L-arginine methyl ester (L-NAME, 100 muM) or soluble guanylate cyclase inhibitor methylene blue (10 muM) administration did not cause a significant alteration on basal tonus of endothelium-intact or -denuded ITA rings. Protamine (50-800 mug/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 prolamine 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). 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. (C) 2003 Elsevier Science B.V. All rights reserved.
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. 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. 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 muM) 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 mug/ml), free hemoglobin (0.1 and 0.5 muM), nitric oxide (NO) blocker N-omega-nitro-L-arginine methyl ester (L-NAME, 100 muM) or soluble guanylate cyclase inhibitor methylene blue (10 muM) administration did not cause a significant alteration on basal tonus of endothelium-intact or -denuded ITA rings. Protamine (50-800 mug/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 prolamine 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). 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. (C) 2003 Elsevier Science B.V. All rights reserved.