Article date: December 2000
By: Dmitry N Derkach, Eikichi Ihara, Katsuya Hirano, Junji Nishimura, Shosuke Takahashi, Hideo Kanaide in Volume 131, Issue 8, pages 1635-1642
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
British Journal of Pharmacology (2000) 131, 1635–1642; doi:10.1038/sj.bjp.0703737
DOI: 10.1038/sj.bjp.0703737
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