Involvement of Endothelial Cyclo‐oxygenase Metabolites in Noradrenaline‐induced Contraction of Rat Coronary Artery

Abstract

1. Noradrenaline (NA; 0.3 micromol/L) caused a contraction of the rat coronary artery that markedly increased in the presence of the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME; 100 micromol/L) and arachidonic acid (1 micromol/L; P < 0.05). 2. The present experiments attempted to elucidate the endothelium dependency of the contraction and to pharmacologically characterize the factors involved in the contraction induced by NA (0.3 micromol/L) in the presence of L-NAME and arachidonic acid in ring preparations of the rat coronary artery. 3. The NA (0.3 micromol/L)-induced contraction was attenuated by a chemical remover of the endothelium (saponin at concentrations of 0.1 and 0.4 mg/mL) in a concentration-dependent manner (P < 0.05). 4. The cyclo-oxygenase (COX)-1 inhibitor flurbiprofen (0.01-1 micromol/L) and the COX-2 inhibitor nimesulide (0.01-1 micromol/L) attenuated the NA-induced contraction in a concentration-dependent manner and the inhibitory effect of flurbiprofen was significantly more potent than that of nimesulide (P < 0.05). The 5-lipoxigenase inhibitor ZM-230487 (1 micromol/L) did not affect the NA-induced contraction. 5. The thromboxane A2 (TXA2) synthetase inhibitor OKY-046 (30 micromol/L) and the TXA2 antagonist S-1452 (0.1-10 micromol/L) did not attenuate the NA-induced contraction. 6. These results indicate that the contraction induced by NA in the rat coronary artery in the presence of L-NAME and arachidonic acid is endothelium dependent and is due to endothelial COX metabolites of arachidonic acid.

Aging-Associated Alterations in Contractility of Rat Mesenteric Lymphatic Vessels

“…After completion of the transmural pressure and imposed flow ranges in APSS (control), the APSS in chamber was replaced with pre‐warmed 38°C APSS containing the nitric oxide synthases (NOS) inhibitor l ‐NAME (Sigma Cat. # N 5751, Sigma‐Aldrich, St. Louis, MO, USA) at 100 μM [1,8,28,31,35,37,38]. The effectiveness of NOS blockade in rat lymphatic vessels induced by application of l ‐NAME at this concentration has been numerously demonstrated by us in previous reports [4,16,20–22].…”

Contraction‐initiated NO‐dependent lymphatic relaxation: a self‐regulatory mechanism in rat thoracic duct

“…In all experiments the input and output pressure were set equally so flow and shear were only generated by phasic contractions of thoracic duct segments. After completion of the transmural pressure range in APSS (control) we set the transmural pressure at 3 cm H 2 O and APSS in the chamber was replaced with APSS containing the nitric oxide synthase inhibitor l ‐NAME (Sigma N5751; 10 −4 m ; Rees et al 1990; Nakaike et al 1995; Mizuno et al 1998; Datte et al 2005; Wang et al 2005; Watanabe et al 2005; Arenas et al 2006) or with the cyclooxygenase inhibitor, indomethacin (Sigma I7378; 10 −5 m ; Nakaike et al 1995; Mizuno et al 1998; Koller et al 1999; Chan & Von Der Weid, 2003; Tsunemoto et al 2003; Chan et al 2004; Kousai et al 2004).…”

Age‐Related Alterations of Active Pumping Mechanisms in Rat Thoracic Duct

“…After completion of the transmural pressure and imposed flow ranges in APSS (control), the APSS in chamber was replaced with APSS containing the nitric oxide (NO) synthase inhibitor l‐NAME (Sigma N 5751) at 10 −4 M [ 2 , 8 , 35 , 37 , 42 , 50 , 51 ]. We used a concentration of l‐NAME at 10 −4 M to be able to compare our data with data obtained in our previous studies [ 19 ] which demonstrated the ability of l‐NAME in this concentration to block completely the contraction‐generated NO‐dependent relaxation in rat thoracic duct.…”