Endothelium-Dependent Contractions Are Associated With Both Augmented Expressionof Prostaglandin H Synthase-1 and Hypersensitivity to Prostaglandin H ₂ in the SHR Aorta

Abstract

Prostaglandin H2 (PGH2 [endoperoxide]) is an immediate product of prostaglandin H (PGH) synthase activity (cyclooxygenase) and a likely candidate to mediate endothelium-dependent contractions evoked by acetylcholine in the aorta of the spontaneously hypertensive rat (SHR). Experiments were designed to investigate whether or not endothelium-dependent contractions were associated with an increased expression of PGH synthase, an augmented acetylcholine-induced release of PGH2, and/or a hypersensitivity of the smooth muscle to endoperoxides in SHR aorta compared with normotensive Wistar-Kyoto (WKY) aorta. In SHR aorta, endothelium-dependent contractions to acetylcholine were abolished by tenidap (10(-8) mol/L), a preferential PGH synthase-1 inhibitor, but slightly impaired by NS-398 (10(-6) mol/L), a preferential PGH synthase-2 inhibitor. PGH synthase-1 expression, which was evaluated by both reverse transcriptase-polymerase chain reaction and Western blotting, was about twofold greater in preparations with endothelium from SHR than from WKY rats. There was no difference in PGH synthase-1 expression between preparations with and those without endothelium in both strains. In SHR but not WKY aortas, acetylcholine (10(-5) mol/L, 5 minutes) caused a significant endothelium-dependent release of PGH2 as measured by gas chromatography/mass spectrometry. PGH2 evoked more potent contractions in rings without endothelium from SHR than from WKY rats, whereas the thromboxane analogue U46619 and prostaglandin F2 alpha caused a comparable response in both preparations. These results show that endothelium-dependent contractions to acetylcholine in SHR aorta are associated with a greater expression of PGH synthase-1, a significant release of PGH2, and a hypersensitivity of the smooth muscle to the endoperoxide.

Acetylcholine and sodium nitroprusside cause long-term inhibition of EDCF-mediated contractions

“…When the presence of endothelium was not tested, ACh evoked endothelium-dependent contractions similar to those reported previously (1,17,36,38). These contractions require the activation of muscarinic receptors (2), activity of cyclooxygenase-1 (COX1) (11), and the activation of TP receptors (1,38). The present results with indomethacin and S-18886 confirm the latter two conclusions.…”

Oxygen‐derived free radicals mediate endothelium‐dependent contractions in femoral arteries of rats with streptozotocin‐induced diabetes

“…This interpretation is consistent with that reached in the aortic endothelium of the spontaneously hypertensive rat (Tang et al, 2007). Cyclooxygenase, the rate-limiting enzyme in the production of endotheliumderived contracting factor, is upregulated in the aorta of spontaneously hypertensive rats and the femoral artery of diabetic rats (Ge et al, 1995(Ge et al, , 1999Shi et al, 2007). Therefore, the increased generation of reactive oxygen species with A23187 in arteries from STZ-treated but not control rats, in accordance with the augmented endothelium-dependent response in the organ chambers, can be attributed to the enhanced presence of endothelial cyclooxygenase.…”

Role of the nitric oxide metabolic pathway and prostanoids in the pathogenesis of endothelial dysfunction and essential hypertension in young men

“…34,35 According to a study by Taddei et al, 36 COX is responsible for ROS formation, which subsequently decreases NO bioavailability. Ge et al 37 postulated that HTN might be associated with higher COX-1 expression and that non-selective blockage of COX may result in lower synthesis of vasoconstrictive prostanoids. Long-term oxidative stress enhances COX-2 expression.…”