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

Abstract

1 Using a method employing front-surface fura-2¯uorometry to measure the cytosolic Ca 2+ concentration, [Ca 2+ ] 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 71, thrombin evoked only early transient relaxation, while at 3 u ml 71 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 [Ca 2+ ] i , while the transient contraction was not associated with a change in [Ca 2+ ] i of smooth muscle cells. 4 A thromboxane A 2 (TXA 2 )/prostaglandin H 2 (PGH 2 ) receptor antagonist (10 75 M ONO-3708) completely inhibited the thrombin-induced contraction, whereas a thromboxane A 2 synthase inhibitor (10 75 M OKY-046) only partly inhibited it. 5 When the thrombin-induced contraction was inhibited by ONO-3708, either pretreatment with N o -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 signi®cant dierence in the concentration-dependent eects 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 TXA 2 and PGH 2 .

Dominant role of an endothelium‐derived hyperpolarizing factor (EDHF)‐like vasodilator in the ciliary vascular bed of the bovine isolated perfused eye

“…Full characterization of this vasoconstrictor response was beyond the scope of this study, but it appears to be endothelium-dependent, since it was not observed when the endothelium was functionally impaired with CHAPS. Previous studies have reported anomalous, endotheliumdependent vasoconstrictor responses in rat aorta (FranchiMicheli et al, 2000) and porcine renal interlobar artery (Derkach et al, 2000). A lower concentration of charybdotoxin (10 nM) had no e ect on perfusion pressure or vasodilatation.…”

Transduction of the N-Terminal Fragments of MYPT1 Enhances Myofilament Ca 2+ Sensitivity in an Intact Coronary Artery

“…The arterial strips without endothelium were prepared as previously described. 24,25 The effects of N-terminal fragments of MYPT1 on [Ca 2ϩ ] i , isometric force, and MLC phosphorylation were examined as previously described. 24 -27 All data were expressed as the meanϮSD.…”

Role of Protease-activated Receptors in the Vascular System

“…NO, endothelium-derived hyperpolarizing factor (EDHF) and prostacyclin were determined to contribute to the relaxation (101,107). In the porcine renal artery, thrombin induces a biphasic response consisting of an initial endothelium-dependent relaxation and a subsequent endothelium-dependent contraction, while having no effect in the absence of endothelium (82). Prostaglandin H2 and thromboxane A2 were shown to contribute to the endothelium-dependent contraction (82).…”