Thrombin causes endothelium-dependent biphasic regulation of vascular tone in the porcine renal interlobar artery

Dmitry N. Derkach, Eikichi Ihara, Katsuya Hirano, Junji Nishimura, Shosuke Takahashi, Hideo Kanaide

研究成果: ジャーナルへの寄稿記事

36 引用 (Scopus)

抄録

1 Using a method employing front-surface fura-2 fluorometry to measure the cytosolic Ca2+ concentration, [Ca2+]i, the mechanism of endothelium-dependent regulation of vascular tone by thrombin was studied in porcine renal interlobar arterial strips. 2 At concentrations lower than 3 u ml-1, thrombin evoked only early transient relaxation, while at 3 u ml-1 and higher concentrations, thrombin caused an early relaxation and a subsequent transient contraction. Both thrombin-induced relaxation and contraction were abolished by removing the endothelium. Similar biphasic responses were observed with a protease-activated receptor-1-activating peptide. 3 Early relaxation was associated with a decrease in [Ca2+]i, while the transient contraction was not associated with a change in [Ca2+]i of smooth muscle cells. 4 A thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist (10-5 M ONO-3708) completely inhibited the thrombin-induced contraction, whereas a thromboxane A2 synthase inhibitor (10-5 M OKY-046) only partly inhibited it. 5 When the thrombin-induced contraction was inhibited by ONO-3708, either pretreatment with Nω-nitro-L-arginine methylester (L-NAME) or an increase in the amount of external K+ to 40 mM did not abolish thrombin-induced relaxation during phenylephrine-induced sustained contraction. However, the combination of pretreatment with L-NAME and an elevation of external K+ to 40 mM completely abolished the relaxation. 6 There was no significant difference in the concentration-dependent effects of thrombin on the initial early relaxation between conditions in which the contractile components either were or were not inhibited. 7 Thrombin is thus considered to mainly activate protease-activated receptor-1 and cause a biphasic response, early relaxation and a transient contraction, in the porcine renal interlobar artery in an endothelium-dependent manner. The thrombin-induced endothelium-dependent relaxation was mediated by nitric oxide and hyperpolarizing factors, while the contraction was mediated by TXA2 and PGH2.

元の言語英語
ページ(範囲)1635-1642
ページ数8
ジャーナルBritish Journal of Pharmacology
131
発行部数8
DOI
出版物ステータス出版済み - 1 1 2000

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Renal Artery
Thrombin
Endothelium
Blood Vessels
Swine
PAR-1 Receptor
Thromboxane A2
NG-Nitroarginine Methyl Ester
Prostaglandin H2 Receptors Thromboxane A2
Prostaglandin H2
Fluorometry
Fura-2
Phenylephrine
Smooth Muscle Myocytes
Arginine
Nitric Oxide
Kidney
Peptides

All Science Journal Classification (ASJC) codes

  • Pharmacology

これを引用

Thrombin causes endothelium-dependent biphasic regulation of vascular tone in the porcine renal interlobar artery. / Derkach, Dmitry N.; Ihara, Eikichi; Hirano, Katsuya; Nishimura, Junji; Takahashi, Shosuke; Kanaide, Hideo.

:: British Journal of Pharmacology, 巻 131, 番号 8, 01.01.2000, p. 1635-1642.

研究成果: ジャーナルへの寄稿記事

Derkach, Dmitry N. ; Ihara, Eikichi ; Hirano, Katsuya ; Nishimura, Junji ; Takahashi, Shosuke ; Kanaide, Hideo. / Thrombin causes endothelium-dependent biphasic regulation of vascular tone in the porcine renal interlobar artery. :: British Journal of Pharmacology. 2000 ; 巻 131, 番号 8. pp. 1635-1642.
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abstract = "1 Using a method employing front-surface fura-2 fluorometry to measure the cytosolic Ca2+ concentration, [Ca2+]i, the mechanism of endothelium-dependent regulation of vascular tone by thrombin was studied in porcine renal interlobar arterial strips. 2 At concentrations lower than 3 u ml-1, thrombin evoked only early transient relaxation, while at 3 u ml-1 and higher concentrations, thrombin caused an early relaxation and a subsequent transient contraction. Both thrombin-induced relaxation and contraction were abolished by removing the endothelium. Similar biphasic responses were observed with a protease-activated receptor-1-activating peptide. 3 Early relaxation was associated with a decrease in [Ca2+]i, while the transient contraction was not associated with a change in [Ca2+]i of smooth muscle cells. 4 A thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist (10-5 M ONO-3708) completely inhibited the thrombin-induced contraction, whereas a thromboxane A2 synthase inhibitor (10-5 M OKY-046) only partly inhibited it. 5 When the thrombin-induced contraction was inhibited by ONO-3708, either pretreatment with Nω-nitro-L-arginine methylester (L-NAME) or an increase in the amount of external K+ to 40 mM did not abolish thrombin-induced relaxation during phenylephrine-induced sustained contraction. However, the combination of pretreatment with L-NAME and an elevation of external K+ to 40 mM completely abolished the relaxation. 6 There was no significant difference in the concentration-dependent effects of thrombin on the initial early relaxation between conditions in which the contractile components either were or were not inhibited. 7 Thrombin is thus considered to mainly activate protease-activated receptor-1 and cause a biphasic response, early relaxation and a transient contraction, in the porcine renal interlobar artery in an endothelium-dependent manner. The thrombin-induced endothelium-dependent relaxation was mediated by nitric oxide and hyperpolarizing factors, while the contraction was mediated by TXA2 and PGH2.",
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T1 - Thrombin causes endothelium-dependent biphasic regulation of vascular tone in the porcine renal interlobar artery

AU - Derkach, Dmitry N.

AU - Ihara, Eikichi

AU - Hirano, Katsuya

AU - Nishimura, Junji

AU - Takahashi, Shosuke

AU - Kanaide, Hideo

PY - 2000/1/1

Y1 - 2000/1/1

N2 - 1 Using a method employing front-surface fura-2 fluorometry to measure the cytosolic Ca2+ concentration, [Ca2+]i, the mechanism of endothelium-dependent regulation of vascular tone by thrombin was studied in porcine renal interlobar arterial strips. 2 At concentrations lower than 3 u ml-1, thrombin evoked only early transient relaxation, while at 3 u ml-1 and higher concentrations, thrombin caused an early relaxation and a subsequent transient contraction. Both thrombin-induced relaxation and contraction were abolished by removing the endothelium. Similar biphasic responses were observed with a protease-activated receptor-1-activating peptide. 3 Early relaxation was associated with a decrease in [Ca2+]i, while the transient contraction was not associated with a change in [Ca2+]i of smooth muscle cells. 4 A thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist (10-5 M ONO-3708) completely inhibited the thrombin-induced contraction, whereas a thromboxane A2 synthase inhibitor (10-5 M OKY-046) only partly inhibited it. 5 When the thrombin-induced contraction was inhibited by ONO-3708, either pretreatment with Nω-nitro-L-arginine methylester (L-NAME) or an increase in the amount of external K+ to 40 mM did not abolish thrombin-induced relaxation during phenylephrine-induced sustained contraction. However, the combination of pretreatment with L-NAME and an elevation of external K+ to 40 mM completely abolished the relaxation. 6 There was no significant difference in the concentration-dependent effects of thrombin on the initial early relaxation between conditions in which the contractile components either were or were not inhibited. 7 Thrombin is thus considered to mainly activate protease-activated receptor-1 and cause a biphasic response, early relaxation and a transient contraction, in the porcine renal interlobar artery in an endothelium-dependent manner. The thrombin-induced endothelium-dependent relaxation was mediated by nitric oxide and hyperpolarizing factors, while the contraction was mediated by TXA2 and PGH2.

AB - 1 Using a method employing front-surface fura-2 fluorometry to measure the cytosolic Ca2+ concentration, [Ca2+]i, the mechanism of endothelium-dependent regulation of vascular tone by thrombin was studied in porcine renal interlobar arterial strips. 2 At concentrations lower than 3 u ml-1, thrombin evoked only early transient relaxation, while at 3 u ml-1 and higher concentrations, thrombin caused an early relaxation and a subsequent transient contraction. Both thrombin-induced relaxation and contraction were abolished by removing the endothelium. Similar biphasic responses were observed with a protease-activated receptor-1-activating peptide. 3 Early relaxation was associated with a decrease in [Ca2+]i, while the transient contraction was not associated with a change in [Ca2+]i of smooth muscle cells. 4 A thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist (10-5 M ONO-3708) completely inhibited the thrombin-induced contraction, whereas a thromboxane A2 synthase inhibitor (10-5 M OKY-046) only partly inhibited it. 5 When the thrombin-induced contraction was inhibited by ONO-3708, either pretreatment with Nω-nitro-L-arginine methylester (L-NAME) or an increase in the amount of external K+ to 40 mM did not abolish thrombin-induced relaxation during phenylephrine-induced sustained contraction. However, the combination of pretreatment with L-NAME and an elevation of external K+ to 40 mM completely abolished the relaxation. 6 There was no significant difference in the concentration-dependent effects of thrombin on the initial early relaxation between conditions in which the contractile components either were or were not inhibited. 7 Thrombin is thus considered to mainly activate protease-activated receptor-1 and cause a biphasic response, early relaxation and a transient contraction, in the porcine renal interlobar artery in an endothelium-dependent manner. The thrombin-induced endothelium-dependent relaxation was mediated by nitric oxide and hyperpolarizing factors, while the contraction was mediated by TXA2 and PGH2.

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