Characteristics of attenuated endothelium‐dependent relaxation seen in rabbit intrapulmonary vein following chronic nitroglycerine administration

Abstract

1 This study was undertaken to determine whether long-term in vivo administration of nitroglycerine (NTG) downregulates the endothelium-dependent relaxation induced by acetylcholine (ACh) in the rabbit intrapulmonary vein and, if so, whether the type 1 angiotensin II receptor (AT 1 R) blocker valsartan normalizes this downregulated relaxation. 2 In strips treated with the cyclooxygenase inhibitor diclofenac, ACh induced a relaxation only when the endothelium was intact. A small part of this ACh-induced relaxation was inhibited by coapplication of two Ca 2 þ -activated K þ -channel blockers (charybdotoxin (CTX) þ apamin) and the greater part of the response was inhibited by the nitric-oxide-synthase inhibitor3 The endothelium-dependent relaxation induced by ACh, but not the endothelium-independent relaxation induced by the nitric oxide donor NOC-7, was significantly reduced in NTG-treated rabbits (versus those in NTG-nontreated control rabbits). The attenuated relaxation was normalized by coapplication of valsartan with the NTG. 4 In the vascular wall, both the amount of localized angiotensin II and the production of superoxide anion were increased by in vivo NTG treatment. These variables were normalized by coapplication of valsartan with the NTG. 5 It is suggested that long-term in vivo administration of NTG downregulates the ACh-induced endothelium-dependent relaxation, mainly through an inhibition of endothelial nitric oxide production in the rabbit intrapulmonary vein. A possible role for AT 1 R is proposed in the mechanism underlying this effect.

Sarpogrelate hydrochloride reduced intimal hyperplasia in experimental rabbit vein graft

“…Once "eNOS uncoupling" has been developed, eNOS becomes dysfunctional and produces superoxide rather than NO. 18,29,30 We found that L-NAME (an inhibitor of eNOS-dependent superoxide production) 29 attenuated superoxide production in the endothelial region (but not the medial region) of vein grafts, suggesting that "eNOS uncoupling" may have developed in our experimental autologous vein grafts. We demonstrated before that celiprolol, ␤-adrenoceptor antagonist inhibited the superoxide production in endothelial cells.…”

“…Fluorescent 12-bit images were acquired and then analyzed using commercial software (LSM5 PASCAL), as previously reported. 18 The total fluorescence intensities obtained from the four areas (36 ϫ 36 pixels square) in each preparation were averaged, and this (ie, one value for each preparation) was used for subsequent analysis.…”

Sarpogrelate protects against high glucose-induced endothelial dysfunction and oxidative stress

“…# p < 0.05, ## p < 0.01 versus the control group; ⁎p < 0.05, ⁎⁎p < 0.01 versus the high glucose group. [47,48]. We found that sarpogrelate may inhibit the development of "eNOS uncoupling", thus leading to an increase in the endotheliumderived NO function.…”

Chronic treatment of hydroxytryptamine type 2a receptor antagonist sarpogrelate hydrochloride modulates the vasoreactivity of serotonin in experimental rabbit vein grafts

“…Fluorescent 12-bit images were acquired and then analyzed using commercial software (LSM5 PASCAL), as previously reported. 13,17 The total fluorescence intensities obtained from four areas (36 ϫ 36 pixels square) in each preparation were averaged, and this (ie, one value for each value) was used for subsequent analysis.…”

“…In some experiments, the endothelium was carefully removed by gentle rubbing of the intimal surface of the vessel using small pieces of razor blade, as previously described. 13,17 Circularly cut strips (0.7-0.8 mm long, 0.2 mm wide) were mounted horizontally in a small chamber and attached to a strain gauge (AE801; SensoNor a.s., Horten, Norway), allowing us to record isometric tension. The chamber (capacity, 0.3 ml) was perfused continuously with Krebs solution at a flow rate of 2 ml/minute.…”